Trial Outcomes & Findings for Everolimus, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma (NCT NCT00553150)

Last Updated: 2020-02-13

Results Overview

Patients were assessed during RT for dose-limiting toxicities (DLT), which were defined as failure to deliver greater than 75% of the planned doses of TMZ or RAD001 during RT, interruption of RT for more than 5 days because of toxicity, or the following: \>= Grade 3 diarrhea or skin rash; \>= Grade 4 neutropenia, leukopenia, or thrombocytopenia; \>= Grade 4 hypertriglyceridemia, hypercholesterolemia, or hyperglycemia despite optimal medial management, other \>= 3 non-hematologic events; or \>= Grade 4 radiation dermatitis. Maximum tolerated dose (MTD) was defined a priori as the highest dose level at which 0 or 1 of 6 patients developed DLTs. The number of patients who developed DLTs are reported here by dose level, with the MTD reported in the statistical analysis section.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

122 participants

Primary outcome timeframe

Up to 49 days

Results posted on

2020-02-13

Participant Flow

Participant milestones

Participant milestones
Measure	Phase I: Cohort/Dose Level 1 (30 mg RAD001) Cycle 1: Everolimus 30 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 30 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase I: Cohort/Dose Level 2 (50 mg RAD001) Cycle 1: Everolimus 50 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 50 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase 1: Cohort/Dose Level 3 (70 mg RAD001) Cycle 1: Everolimus 70 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 70 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase II Cycle 1: Everolimus 70 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 70 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.
Overall Study STARTED	6	6	6	104
Overall Study COMPLETED	6	6	6	100
Overall Study NOT COMPLETED	0	0	0	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I: Cohort/Dose Level 1 (30 mg RAD001) Cycle 1: Everolimus 30 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 30 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase I: Cohort/Dose Level 2 (50 mg RAD001) Cycle 1: Everolimus 50 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 50 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase 1: Cohort/Dose Level 3 (70 mg RAD001) Cycle 1: Everolimus 70 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 70 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase II Cycle 1: Everolimus 70 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 70 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.
Overall Study Withdrawal by Subject	0	0	0	2
Overall Study Protocol Violation	0	0	0	1
Overall Study Ineligible	0	0	0	1

Baseline Characteristics

Everolimus, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I n=18 Participants Cycle 1: Everolimus (either: 30, 50, or 70 mg) days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus (either: 30, 50, or 70 mg)/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase II n=104 Participants Cycle 1: Everolimus 70 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 70 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Total n=122 Participants Total of all reporting groups
Age, Continuous	57.5 years n=5 Participants	61 years n=7 Participants	60.5 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	50 Participants n=7 Participants	59 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	54 Participants n=7 Participants	63 Participants n=5 Participants
Region of Enrollment United States	18 participants n=5 Participants	104 participants n=7 Participants	122 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 49 days

Population: Eighteen patients were enrolled in Phase I of the study to determine the maximum tolerated dose (MTD). The dosage of RAD001 was escalated in cohorts of 6 patients.

Outcome measures

Outcome measures
Measure	Phase I: Dose Level 0 n=6 Participants Cycle 1: Everolimus 30 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 30 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase I: Dose Level 1 n=6 Participants Cycle 1: Everolimus 50 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 50 mg)/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase I: Dose Level 2 n=6 Participants Cycle 1: Everolimus 70 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 70 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.
Maximum Tolerated Dose (MTD) of Everolimus (RAD001) in Combination With Temozolomide (TMZ) and 3D-conformal Radiotherapy (RT) or Intensity-modulated Radiotherapy (IMRT) Followed by Adjuvant TMZ With or Without RAD001 (Phase I)	1 participants who developed DLTs	1 participants who developed DLTs	1 participants who developed DLTs

PRIMARY outcome

Timeframe: at 12 months

The primary endpoint is overall survival at 12 months (OS12) after entry into this study. The proportion of successes will be estimated using the binomial point estimator (number of successes divided by the total number of evaluable patients) and the binomial 95% confidence interval estimated. A patient who is evaluable and survive more than 12 months (i.e. 365 days or more) after start of therapy will be classified as a "success". Patients who die within 12 months after start of therapy will be considered to have "failed".

Outcome measures

Outcome measures
Measure	Phase I: Dose Level 0 n=100 Participants Cycle 1: Everolimus 30 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 30 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase I: Dose Level 1 Cycle 1: Everolimus 50 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 50 mg)/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase I: Dose Level 2 Cycle 1: Everolimus 70 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 70 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.
Overall Survival at 12 Months (Phase II)	0.64 proportion of participants Interval 0.553 to 0.741	—	—

SECONDARY outcome

Timeframe: Up to 5 years

Population: Of the 11 patients with measurable residual disease and pre-everolimus FLT-PET imaging, 2 did not have a second FLT-PET scan performed due to technical difficulties with FLT production, leaving 9 patients who could be assessed for changes in FLT uptake.

The response rate is defined as the percentage of patients receiving F-fluorothymidine positron emission tomography (FLT-PET) imaging whose cancer shrinks or disappears after treatment. A reduction in standardized uptake value (SUV) of 30% or greater in the T1-post-gadolinium scan volume of interest (T1-gad VOI) or the total tumor VOI will be considered a responsive tumor.

Outcome measures

Outcome measures
Measure	Phase I: Dose Level 0 n=9 Participants Cycle 1: Everolimus 30 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 30 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase I: Dose Level 1 Cycle 1: Everolimus 50 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 50 mg)/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase I: Dose Level 2 Cycle 1: Everolimus 70 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 70 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.
Response Rate, as Measured in Patients Receiving FLT-PET Imaging (Phase II)	44.4 percentage of participants Interval 15.3 to 77.3	—	—

SECONDARY outcome

Timeframe: Up to 5 years

Time-to-disease progression is defined as the time from start of study therapy to documentation of disease progression. Patients who die without documentation of progression will be considered to have had tumor progression at the time of death unless there is documented evidence that no progression occurred before death. Patients who fail to return for evaluation after beginning therapy will be censored for progression on the last day of therapy. Patients who experience major treatment violations will be censored for progression on the date of treatment violation occurred. The time-to-progression distribution will be estimated using the Kaplan-Meier method. Progression is defined as at least a 25% increase in product of perpendicular diameters of contrast enhancement or mass or unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians or appearance of new lesions.

Outcome measures

Outcome measures
Measure	Phase I: Dose Level 0 n=100 Participants Cycle 1: Everolimus 30 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 30 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase I: Dose Level 1 Cycle 1: Everolimus 50 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 50 mg)/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase I: Dose Level 2 Cycle 1: Everolimus 70 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 70 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.
Time to Progression (Phase II)	6.4 months Interval 5.4 to 9.0	—	—

SECONDARY outcome

Timeframe: at 6 months

Progression-free-survival at 6 months: is the proportion of patients alive and progression-free at 6 months after start of regimen. This proportion will be estimated using the binomial point estimator and the binomial 95% confidence interval estimated. Progression is defined as at least a 25% increase in product of perpendicular diameters of contrast enhancement or mass or unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians or appearance of new lesions.

Outcome measures

Outcome measures
Measure	Phase I: Dose Level 0 n=100 Participants Cycle 1: Everolimus 30 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 30 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase I: Dose Level 1 Cycle 1: Everolimus 50 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 50 mg)/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase I: Dose Level 2 Cycle 1: Everolimus 70 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 70 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.
Progression-free-survival at 6 Months (Phase II)	0.52 proportion of participants Interval 0.431 to 0.628	—	—

SECONDARY outcome

Timeframe: Up to 15 years

Overall survival: The overall survival or survival time is defined as the time from registration to death due to any cause. The distribution of overall survival will be estimated using the method of Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Phase I: Dose Level 0 n=100 Participants Cycle 1: Everolimus 30 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 30 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase I: Dose Level 1 Cycle 1: Everolimus 50 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 50 mg)/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase I: Dose Level 2 Cycle 1: Everolimus 70 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 70 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.
Overall Survival Time	15.8 months Interval 13.0 to 20.3	—	—

Adverse Events

Phase I

Serious events: 5 serious events

Other events: 18 other events

Deaths: 0 deaths

Phase II

Serious events: 32 serious events

Other events: 99 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Jann N. Sarkaria, M.D.

Mayo Clinic

Phone: 507/284-3559

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Phase I n=18 participants at risk Cycle 1: Everolimus (either: 30, 50, or 70 mg) days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus (either: 30, 50, or 70 mg)/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase II n=101 participants at risk Cycle 1: Everolimus 70 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 70 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	2.0% 2/101 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Blood and lymphatic system disorders Hemoglobin decreased	5.6% 1/18 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	3.0% 3/101 • Number of events 3 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Cardiac disorders Sinus bradycardia	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Cardiac disorders Sinus tachycardia	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	2.0% 2/101 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Colonic perforation	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Diarrhea	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	2.0% 2/101 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Dysphagia	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Ear, nose and throat examination abnormal	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	2.0% 2/101 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Mucositis oral	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	2.0% 2/101 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Nausea	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	3.0% 3/101 • Number of events 5 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Oral pain	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Vomiting	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
General disorders Chills	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
General disorders Death	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
General disorders Disease progression	5.6% 1/18 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
General disorders Fatigue	5.6% 1/18 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	3.0% 3/101 • Number of events 4 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
General disorders Fever	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	2.0% 2/101 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
General disorders Localized edema	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Infections and infestations Anorectal infection	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Infections and infestations Pneumonia	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	4.0% 4/101 • Number of events 4 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Infections and infestations Urinary tract infection	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	2.0% 2/101 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Investigations Alanine aminotransferase increased	5.6% 1/18 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.00% 0/101 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Investigations Aspartate aminotransferase increased	5.6% 1/18 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.00% 0/101 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Investigations Bilirubin increased	5.6% 1/18 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.00% 0/101 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Investigations Leukocyte count decreased	5.6% 1/18 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	3.0% 3/101 • Number of events 3 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Investigations Neutrophil count decreased	5.6% 1/18 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	9.9% 10/101 • Number of events 11 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Investigations Platelet count decreased	5.6% 1/18 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	8.9% 9/101 • Number of events 9 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Investigations Serum cholesterol increased	5.6% 1/18 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	2.0% 2/101 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Metabolism and nutrition disorders Anorexia	5.6% 1/18 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Metabolism and nutrition disorders Blood glucose increased	5.6% 1/18 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Metabolism and nutrition disorders Dehydration	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	5.0% 5/101 • Number of events 6 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Metabolism and nutrition disorders Serum albumin decreased	5.6% 1/18 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.00% 0/101 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Metabolism and nutrition disorders Serum calcium decreased	5.6% 1/18 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.00% 0/101 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Metabolism and nutrition disorders Serum phosphate decreased	5.6% 1/18 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Metabolism and nutrition disorders Serum sodium decreased	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Metabolism and nutrition disorders Serum triglycerides increased	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Musculoskeletal and connective tissue disorders Muscle weakness	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	3.0% 3/101 • Number of events 3 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.

Other adverse events
Measure	Phase I n=18 participants at risk Cycle 1: Everolimus (either: 30, 50, or 70 mg) days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus (either: 30, 50, or 70 mg)/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.	Phase II n=101 participants at risk Cycle 1: Everolimus 70 mg days 1, 8, and weekly through radiation therapy (RT). Starting between day 8 and 15 RT was 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Everolimus. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Everolimus 70 mg/week (Days 1, 8, 15 and 22 for each cycle, until progression). Prophylaxis for pneumocystis carinii pneumonia (PCP) was required starting cycle 1 day1.
Blood and lymphatic system disorders Hemoglobin decreased	11.1% 2/18 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	8.9% 9/101 • Number of events 17 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Blood and lymphatic system disorders Hemolysis	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Ear and labyrinth disorders Hearing loss	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Ear and labyrinth disorders Middle ear inflammation	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Endocrine disorders Cushingoid	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Eye disorders Diplopia	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Eye disorders Vision blurred	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	3.0% 3/101 • Number of events 3 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Eye disorders Watering eyes	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Abdominal pain	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Constipation	11.1% 2/18 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	5.0% 5/101 • Number of events 5 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Diarrhea	38.9% 7/18 • Number of events 11 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	34.7% 35/101 • Number of events 79 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Dyspepsia	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	2.0% 2/101 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Dysphagia	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	2.0% 2/101 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Ear, nose and throat examination abnormal	5.6% 1/18 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	5.9% 6/101 • Number of events 6 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Gastritis	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Mucositis oral	5.6% 1/18 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	5.0% 5/101 • Number of events 5 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Nausea	44.4% 8/18 • Number of events 20 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	67.3% 68/101 • Number of events 166 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Rectal pain	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Gastrointestinal disorders Vomiting	5.6% 1/18 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	4.0% 4/101 • Number of events 4 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
General disorders Edema limbs	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	6.9% 7/101 • Number of events 11 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
General disorders Facial pain	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
General disorders Fatigue	33.3% 6/18 • Number of events 6 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	44.6% 45/101 • Number of events 83 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
General disorders Fever	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	2.0% 2/101 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
General disorders Irritability	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
General disorders Localized edema	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
General disorders Pain	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Infections and infestations Bronchitis	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Infections and infestations Infection	5.6% 1/18 • Number of events 4 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	3.0% 3/101 • Number of events 3 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Infections and infestations Mucosal infection	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Infections and infestations Opportunistic infection	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	3.0% 3/101 • Number of events 3 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Infections and infestations Peripheral nerve infection	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Infections and infestations Pharyngitis	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Infections and infestations Pneumonia	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Infections and infestations Skin infection	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	2.0% 2/101 • Number of events 3 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Infections and infestations Upper aerodigestive tract infection	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	2.0% 2/101 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Infections and infestations Urinary tract infection	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	2.0% 2/101 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Injury, poisoning and procedural complications Dermatitis radiation	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Injury, poisoning and procedural complications Vascular access complication	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	2.0% 2/101 • Number of events 2 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	0.99% 1/101 • Number of events 1 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.
Investigations Alanine aminotransferase increased	0.00% 0/18 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.	5.9% 6/101 • Number of events 11 • Adverse events were assessed weekly during Cycle 1, at the end of RT, prior to cycles 3-8, and during treatment with everolimus only until progression (Cycles ≥9). Only patients who had completed one cycle of treatment and completed an adverse event form were included in this adverse event table; Up to 5 years. CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized until September 30, 2010. CTCAE version 4.0 will be utilized for expedited adverse event reporting only, beginning October 1, 2010. All appropriate treatment areas should have access to a copy of the CTCAE v4.0.