Trial Outcomes & Findings for Efficacy of Hypofractionated XRT w/Bev. + Temozolomide for Recurrent Gliomas (NCT NCT01478321)

NCT ID: NCT01478321

Last Updated: 2020-03-12

Results Overview

Data will be analyzed using Kaplan-Meier curves. OS is defined as the time from first re-irradiation treatment until death from any cause.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 54 participants
• Primary outcome timeframe: From treatment initiation and every 8 weeks for up to 53.5 months
• Results posted on: 2020-03-12

Participant Flow

The study opened for accrual on November 14, 2011 with an accrual goal of up to 77 patients and the first patient being enrolled on December 14, 2011. The study was closed permanently on March 24, 2017 due to low accrual with 54 patients treated on the study.

Participant milestones

Measure	Treatment (Radiation, Chemotherapy, Monoclonal Antibody) CONCURRENT THERAPY: Patients undergo hypofractionated radiation therapy 5 days a week beginning on Day 0. Patients also receive temozolomide PO QD and bevacizumab IV over 30-90 minutes once every 2 weeks beginning on Days -3 to 0. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity. ADJUVANT THERAPY: Beginning 2 weeks after completion of radiation therapy, patients receive temozolomide PO QD for 6 weeks and bevacizumab IV over 30-90 minutes once every 2 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Temozolomide: Given PO Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy Bevacizumab: Given IV Questionnaire administration: Ancillary studies
Concurrent Therapy (5 Weeks) STARTED	54
Concurrent Therapy (5 Weeks) COMPLETED	38
Concurrent Therapy (5 Weeks) NOT COMPLETED	16
Started Adjuvant Therapy STARTED	38
Started Adjuvant Therapy Completed First Cycle	37
Started Adjuvant Therapy COMPLETED	37
Started Adjuvant Therapy NOT COMPLETED	1
Adjuvant Therapy Until PD or Toxicity STARTED	37
Adjuvant Therapy Until PD or Toxicity Went on to Cycle 2 +	27
Adjuvant Therapy Until PD or Toxicity COMPLETED	27
Adjuvant Therapy Until PD or Toxicity NOT COMPLETED	10
Follow-up Until Death or 12.31.18 Occurs STARTED	54
Follow-up Until Death or 12.31.18 Occurs COMPLETED	54
Follow-up Until Death or 12.31.18 Occurs NOT COMPLETED	0

Reasons for withdrawal

Measure	Treatment (Radiation, Chemotherapy, Monoclonal Antibody) CONCURRENT THERAPY: Patients undergo hypofractionated radiation therapy 5 days a week beginning on Day 0. Patients also receive temozolomide PO QD and bevacizumab IV over 30-90 minutes once every 2 weeks beginning on Days -3 to 0. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity. ADJUVANT THERAPY: Beginning 2 weeks after completion of radiation therapy, patients receive temozolomide PO QD for 6 weeks and bevacizumab IV over 30-90 minutes once every 2 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Temozolomide: Given PO Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy Bevacizumab: Given IV Questionnaire administration: Ancillary studies
Concurrent Therapy (5 Weeks) Adverse Event	4
Concurrent Therapy (5 Weeks) Death	2
Concurrent Therapy (5 Weeks) Withdrawal by Subject	5
Concurrent Therapy (5 Weeks) Progressive Disease	5
Started Adjuvant Therapy Withdrawal by Subject	1
Adjuvant Therapy Until PD or Toxicity Death	1
Adjuvant Therapy Until PD or Toxicity Withdrawal by Subject	1
Adjuvant Therapy Until PD or Toxicity Progressive Disease	8

Baseline Characteristics

Efficacy of Hypofractionated XRT w/Bev. + Temozolomide for Recurrent Gliomas

Baseline characteristics by cohort

Measure	Treatment (Radiation, Chemotherapy, Monoclonal Antibody) n=54 Participants CONCURRENT THERAPY: Patients undergo hypofractionated radiation therapy 5 days a week beginning on Day 0. Patients also receive temozolomide PO QD and bevacizumab IV over 30-90 minutes once every 2 weeks beginning on Days -3 to 0. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity. ADJUVANT THERAPY: Beginning 2 weeks after completion of radiation therapy, patients receive temozolomide PO QD for 6 weeks and bevacizumab IV over 30-90 minutes once every 2 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Temozolomide: Given PO Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy Bevacizumab: Given IV Questionnaire administration: Ancillary studies
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	46 Participants n=5 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants
Sex: Female, Male Male	37 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	48 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	48 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	54 Participants n=5 Participants
Bevacizumab-Naive Recurrent GBM	8 Participants n=5 Participants
Bevacizumab-Exposed Recurrent GBM	36 Participants n=5 Participants
Bevacizumab-Naive Recurrent Anaplastic Glioma	3 Participants n=5 Participants
Bevacizumab-Exposed Recurrent Anaplastic Glioma	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: From treatment initiation and every 8 weeks for up to 53.5 months

Population: All patients were eligible for this outcome measure with 2 patients not experiencing the event at time of analysis.

Data will be analyzed using Kaplan-Meier curves. OS is defined as the time from first re-irradiation treatment until death from any cause.

Outcome measures

Measure

Treatment (Radiation, Chemotherapy, Monoclonal Antibody) n=54 Participants CONCURRENT THERAPY: Patients undergo hypofractionated radiation therapy 5 days a week beginning on Day 0. Patients also receive temozolomide PO QD and bevacizumab IV over 30-90 minutes once every 2 weeks beginning on Days -3 to 0. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity. ADJUVANT THERAPY: Beginning 2 weeks after completion of radiation therapy, patients receive temozolomide PO QD for 6 weeks and bevacizumab IV over 30-90 minutes once every 2 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Temozolomide: Given PO Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy Bevacizumab: Given IV Questionnaire administration: Ancillary studies

Overall Survival (OS) for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab.

8.5 Months Interval 6.4 to 9.5

SECONDARY outcome

Timeframe: Completed before treatment (baseline) after Cycle 1 (approximately week 15) and Cycle 2 (approximately week 23)of adjuvant treatment and at the end of treatment (up to 7 cycles of adjuvant treatment, where 1 cycle =8 weeks)

Population: Only patients where sufficient data was collected for analysis were considered evaluable for this endpoint and included.

Questionnaires were completed before treatment (baseline) at the end of treatment (EOT) and after Cycle 1 and Cycle 2 of treatment (Initial phase of treatment =5 weeks + approximately 2 weeks recovery then adjuvant therapy where 1 cycle = 8 weeks). The following questionnaires were completed by patients to evaluate quality of life (QOL) at these timepoints:

FACT-Fatigue - scores from 1 to 4 with 1=not at all and 4=very much, the higher the score the more fatigue reported by the patient.

FACT-Brain (FACT Br) which included - Physcial Well-being (PWB), Social/Family Well-being (SWB), Emotional Well-being (EWB), and Functional Well-being (FWB).

Patients gave scores from 0 to 4 with 0=not at all and 4=very much, the higher the score the better the QOL reported by the patient.

Outcome measures

Measure	Treatment (Radiation, Chemotherapy, Monoclonal Antibody) n=42 Participants CONCURRENT THERAPY: Patients undergo hypofractionated radiation therapy 5 days a week beginning on Day 0. Patients also receive temozolomide PO QD and bevacizumab IV over 30-90 minutes once every 2 weeks beginning on Days -3 to 0. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity. ADJUVANT THERAPY: Beginning 2 weeks after completion of radiation therapy, patients receive temozolomide PO QD for 6 weeks and bevacizumab IV over 30-90 minutes once every 2 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Temozolomide: Given PO Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy Bevacizumab: Given IV Questionnaire administration: Ancillary studies
Patient Reported Quality of Life (QOL) FACT-BR Total : Baseline	130.4 score on a scale Standard Deviation 29.6
Patient Reported Quality of Life (QOL) FACT-BR Total : Post Cycle 1	133.0 score on a scale Standard Deviation 18.8
Patient Reported Quality of Life (QOL) FACT-BR PWB : EOT	21.6 score on a scale Standard Deviation 5.0
Patient Reported Quality of Life (QOL) FACT-BR SWB : Post Cycle 1	23.0 score on a scale Standard Deviation 3.2
Patient Reported Quality of Life (QOL) FACT-BR Total : EOT	106.9 score on a scale Standard Deviation 61.4
Patient Reported Quality of Life (QOL) FACT-BR Total : Post Cycle 2	131.4 score on a scale Standard Deviation 10.2
Patient Reported Quality of Life (QOL) FACT-BR PWB : Baseline	22.0 score on a scale Standard Deviation 5.0
Patient Reported Quality of Life (QOL) FACT-BR PWB : Post Cycle 1	21.7 score on a scale Standard Deviation 4.4
Patient Reported Quality of Life (QOL) FACT-BR PWB : Post Cycle 2	21.1 score on a scale Standard Deviation 3.9
Patient Reported Quality of Life (QOL) FACT-BR SWB : Baseline	22.2 score on a scale Standard Deviation 5.4
Patient Reported Quality of Life (QOL) FACT-BR SWB : EOT	22.9 score on a scale Standard Deviation 4.3
Patient Reported Quality of Life (QOL) FACT-BR SWB : Post Cycle 2	23.7 score on a scale Standard Deviation 3.0
Patient Reported Quality of Life (QOL) FACT-BR EWB : Baseline	15.9 score on a scale Standard Deviation 5.7
Patient Reported Quality of Life (QOL) FACT-BR EWB : EOT	16.5 score on a scale Standard Deviation 4.9
Patient Reported Quality of Life (QOL) FACT-BR EWB : Post Cycle 1	17.2 score on a scale Standard Deviation 3.3
Patient Reported Quality of Life (QOL) FACT-BR EWB : Post Cycle 2	17.7 score on a scale Standard Deviation 3.0
Patient Reported Quality of Life (QOL) FACT-FWB : Baseline	15.9 score on a scale Standard Deviation 6.9
Patient Reported Quality of Life (QOL) FACT-FWB : EOT	17.8 score on a scale Standard Deviation 4.8
Patient Reported Quality of Life (QOL) FACT-FWB : Post Cycle 1	17.0 score on a scale Standard Deviation 4.8
Patient Reported Quality of Life (QOL) FACT-FWB: Post Cycle 2	18.3 score on a scale Standard Deviation 3.3
Patient Reported Quality of Life (QOL) FACIT-Fatigue: Baseline	35.6 score on a scale Standard Deviation 10.3
Patient Reported Quality of Life (QOL) FACIT-Fatigue: EOT	30.3 score on a scale Standard Deviation 12.5
Patient Reported Quality of Life (QOL) FACIT-Fatigue: Post Cycle 1	34.4 score on a scale Standard Deviation 7.7
Patient Reported Quality of Life (QOL) FACIT-Fatigue: Post Cycle 2	36.2 score on a scale Standard Deviation 7.9

SECONDARY outcome

Timeframe: Completed weekly during initial phase of 5 weeks and 2 weeks recovery, then every cycle during adjuvant therapy where 1 cycle =8 weeks (for up to 7 cycles)

Population: All patients that received at least one dose of treatment on study were eligible for this outcome measure

Toxicity will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria on Day 1 of every treatment cycle and by patient report while on study treatment and up to 30 days after the last treatment. Grade 1 - 4 adverse events (AE) where the relationship between the AE and at least one of the study drugs were considered to be definite, probable or possible, were collected and graded as:

Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE

Outcome measures

Measure	Treatment (Radiation, Chemotherapy, Monoclonal Antibody) n=54 Participants CONCURRENT THERAPY: Patients undergo hypofractionated radiation therapy 5 days a week beginning on Day 0. Patients also receive temozolomide PO QD and bevacizumab IV over 30-90 minutes once every 2 weeks beginning on Days -3 to 0. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity. ADJUVANT THERAPY: Beginning 2 weeks after completion of radiation therapy, patients receive temozolomide PO QD for 6 weeks and bevacizumab IV over 30-90 minutes once every 2 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Temozolomide: Given PO Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy Bevacizumab: Given IV Questionnaire administration: Ancillary studies
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Thrombocytopenia : Grade 1	8 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Thrombocytopenia : Grade 2	1 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Epistaxis : Grade 1	3 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Epistaxis : Grade 2	0 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Epistaxis : Grade 3	0 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Epistaxis : Grade 4	0 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Thromboembolism : Grade 1	0 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Lymphopenia : Grade 1	4 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Lymphopenia : Grade 2	12 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Lymphopenia : Grade 3	4 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Lymphopenia : Grade 4	1 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Fatigue : Grade 1	9 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Fatigue : Grade 2	5 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Fatigue : Grade 3	1 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Fatigue : Grade 4	0 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Thrombocytopenia : Grade 3	2 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Thrombocytopenia : Grade 4	1 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Anemia : Grade 1	7 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Anemia : Grade 2	1 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Anemia : Grade 3	1 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Anemia : Grade 4	0 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Constipation : Grade 1	8 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Constipation : Grade 2	1 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Constipation : Grade 3	0 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Constipation : Grade 4	0 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Hypertension : Grade 1	0 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Hypertension : Grade 2	6 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Hypertension : Grade 3	1 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Hypertension : Grade 4	0 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Neutropenia : Grade 1	2 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Neutropenia : Grade 2	3 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Neutropenia : Grade 3	0 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Neutropenia : Grade 4	0 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Thromboembolism : Grade 2	1 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Thromboembolism : Grade 3	1 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Thromboembolism : Grade 4	0 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Proteinuria : Grade 1	0 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Proteinuria : Grade 2	0 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Proteinuria : Grade 3	2 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Proteinuria : Grade 4	0 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Wound Complication : Grade 1	0 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Wound Complication : Grade 2	0 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Wound Complication : Grade 3	2 participants
Safety Profile for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Wound Complication : Grade 4	0 participants

SECONDARY outcome

Timeframe: At 6 and 12 months after the start of treatment

Population: Only evaluable patients that completed RT treatment, with follow up imaging and data for progression were included in this endpoint.

Progression Free Survival is defined as the time from the first study treatment to the first occurrence of disease progression or death. Data will be analyzed using Kaplan-Meier curves. Tumor measurements and assessments will be based on Updated Response Assessment Criteria of High Grade Gliomas- Neuro-Oncology Working Group (RANO criteria). Tumor assessments may include either a CT or MRI scan of the brain, however the same method should be used throughout the treatment period for each patient. In general, progressive disease is defined as any of the following: ≥ 25% increase in T1 gadolinium enhancing disease, increase in T2/Flair, new lesions present or decrease in clinical status

Outcome measures

Measure	Treatment (Radiation, Chemotherapy, Monoclonal Antibody) n=42 Participants CONCURRENT THERAPY: Patients undergo hypofractionated radiation therapy 5 days a week beginning on Day 0. Patients also receive temozolomide PO QD and bevacizumab IV over 30-90 minutes once every 2 weeks beginning on Days -3 to 0. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity. ADJUVANT THERAPY: Beginning 2 weeks after completion of radiation therapy, patients receive temozolomide PO QD for 6 weeks and bevacizumab IV over 30-90 minutes once every 2 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Temozolomide: Given PO Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy Bevacizumab: Given IV Questionnaire administration: Ancillary studies
Percentage of Patients With Progression Free Survival (PFS) at 6 Months and 12 Months 6 Months	48 percentage of patients with PFS
Percentage of Patients With Progression Free Survival (PFS) at 6 Months and 12 Months 12 Months	12 percentage of patients with PFS

POST_HOC outcome

Timeframe: Every 8 weeks from the start of study treatment. Median time from beginning of initial radiation treatment was 25.3 months (range 8.1-82.4 months)

Best response is measured by CT/MRI and assessed by Updated Response Assessment Criteria of High Grade Gliomas- Neuro-Oncology Working Group (RANO criteria).

In general best response will be defined as one of the following:

Complete Response: No T1 gadolinium enhancing disease, stable or decreasing T2/FLAIR, no new lesions, no corticosteroid use and stable or increasing clinical status Partial Response: ≥ 50% decrease in T1 gadolinium enhancing disease, stable or decreasing T2/FLAIR, no new lesions,stable or decreasing use of corticosteroids, and stable or increasing clinical status Stable Disease: < 50% decrease but < 25% increase T1 gadolinium enhancing disease, stable or decreasing T2/FLAIR, no new lesions,stable or decreasing use of corticosteroids, and stable or increasing clinical status Progressive Disease is any of the following: ≥ 25% increase in T1 gadolinium enhancing disease, increase in T2/Flair, new lesions present or decrease in clinical status

Outcome measures

Measure	Treatment (Radiation, Chemotherapy, Monoclonal Antibody) n=54 Participants CONCURRENT THERAPY: Patients undergo hypofractionated radiation therapy 5 days a week beginning on Day 0. Patients also receive temozolomide PO QD and bevacizumab IV over 30-90 minutes once every 2 weeks beginning on Days -3 to 0. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity. ADJUVANT THERAPY: Beginning 2 weeks after completion of radiation therapy, patients receive temozolomide PO QD for 6 weeks and bevacizumab IV over 30-90 minutes once every 2 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Temozolomide: Given PO Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy Bevacizumab: Given IV Questionnaire administration: Ancillary studies
Response of Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Complete Response	3 Participants
Response of Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Partial Response	10 Participants
Response of Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Stable Disease	28 Participants
Response of Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Progressive Disease	9 Participants
Response of Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab Not Evaluable	4 Participants

POST_HOC outcome

Timeframe: Range from treatment initiation 0.4-26.9 months

Population: Only evaluable patients that completed RT treatment, with follow up imaging and data for progression were included in this endpoint.

Progression Free Survival (PFS) is defined as the time from the first study treatment to the first occurrence of disease progression or death. Data will be analyzed using Kaplan-Meier curves. Tumor measurements and assessments will be based on Updated Response Assessment Criteria of High Grade Gliomas- Neuro-Oncology Working Group (RANO criteria). Tumor assessments may include either a CT or MRI scan of the brain, however the same method should be used throughout the treatment period for each patient. In general, progressive disease is defined as any of the following: ≥ 25% increase in T1 gadolinium enhancing disease, increase in T2/Flair, new lesions present or decrease in clinical status.

Outcome measures

Measure

Treatment (Radiation, Chemotherapy, Monoclonal Antibody) n=42 Participants CONCURRENT THERAPY: Patients undergo hypofractionated radiation therapy 5 days a week beginning on Day 0. Patients also receive temozolomide PO QD and bevacizumab IV over 30-90 minutes once every 2 weeks beginning on Days -3 to 0. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity. ADJUVANT THERAPY: Beginning 2 weeks after completion of radiation therapy, patients receive temozolomide PO QD for 6 weeks and bevacizumab IV over 30-90 minutes once every 2 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Temozolomide: Given PO Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy Bevacizumab: Given IV Questionnaire administration: Ancillary studies

Median Progression Free Survival (PFS) for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab

5.5 Months Interval 0.4 to 26.9

POST_HOC outcome

Timeframe: At 6 and 12 months from start of treatment

Data will be analyzed using Kaplan-Meier curves. OS is defined as the time from first re-irradiation treatment until death from any cause. Percentages of patients alive at that 6 months and 12 months will be calculated from the Kaplan-Meier curve.

Outcome measures

Measure	Treatment (Radiation, Chemotherapy, Monoclonal Antibody) n=54 Participants CONCURRENT THERAPY: Patients undergo hypofractionated radiation therapy 5 days a week beginning on Day 0. Patients also receive temozolomide PO QD and bevacizumab IV over 30-90 minutes once every 2 weeks beginning on Days -3 to 0. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity. ADJUVANT THERAPY: Beginning 2 weeks after completion of radiation therapy, patients receive temozolomide PO QD for 6 weeks and bevacizumab IV over 30-90 minutes once every 2 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Temozolomide: Given PO Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy Bevacizumab: Given IV Questionnaire administration: Ancillary studies
Overall Survival (OS) at 6 Months and 12 Months for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab. 6 Months	67 percentage of patients alive
Overall Survival (OS) at 6 Months and 12 Months for Patients With Recurrent High Grade Malignant Gliomas Treated With Concurrent Radiation, Temozolomide, and Bevacizumab Followed by Adjuvant Temozolomide and Bevacizumab. 12 Months	28 percentage of patients alive

Adverse Events

Treatment (Radiation, Chemotherapy, Monoclonal Antibody)

Serious events: 20 serious events

Other events: 54 other events

Deaths: 52 deaths

Serious adverse events

Measure	Treatment (Radiation, Chemotherapy, Monoclonal Antibody) n=54 participants at risk CONCURRENT THERAPY: Patients undergo hypofractionated radiation therapy 5 days a week beginning on Day 0. Patients also receive temozolomide PO QD and bevacizumab IV over 30-90 minutes once every 2 weeks beginning on Days -3 to 0. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity. ADJUVANT THERAPY: Beginning 2 weeks after completion of radiation therapy, patients receive temozolomide PO QD for 6 weeks and bevacizumab IV over 30-90 minutes once every 2 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Temozolomide: Given PO Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy Bevacizumab: Given IV Questionnaire administration: Ancillary studies
Metabolism and nutrition disorders Anorexia	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Vascular disorders Thromboembolic Event	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Musculoskeletal and connective tissue disorders Generalized Muscle Weakness	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Musculoskeletal and connective tissue disorders Muscle Weakness Right-sided	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Infections and infestations Wound Infection	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Seizure	7.4% 4/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Metabolism and nutrition disorders Dehydration	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Infections and infestations Upper Respiratory Infection	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Gastrointestinal disorders Hemorrhoidal hemorrhage	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Injury, poisoning and procedural complications Fall	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Depressed Level of Consciousness	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
General disorders Death NOS	9.3% 5/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Investigations Platelet Count Decreased	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Infections and infestations Hepatic Infection	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Respiratory, thoracic and mediastinal disorders Hiccups	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Injury, poisoning and procedural complications Wound Complication	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Headache	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Metabolism and nutrition disorders Hyponatremia	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.

Other adverse events

Measure	Treatment (Radiation, Chemotherapy, Monoclonal Antibody) n=54 participants at risk CONCURRENT THERAPY: Patients undergo hypofractionated radiation therapy 5 days a week beginning on Day 0. Patients also receive temozolomide PO QD and bevacizumab IV over 30-90 minutes once every 2 weeks beginning on Days -3 to 0. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity. ADJUVANT THERAPY: Beginning 2 weeks after completion of radiation therapy, patients receive temozolomide PO QD for 6 weeks and bevacizumab IV over 30-90 minutes once every 2 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Temozolomide: Given PO Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy Bevacizumab: Given IV Questionnaire administration: Ancillary studies
Blood and lymphatic system disorders Anemia	22.2% 12/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Cardiac disorders Sinus bradycardia	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Cardiac disorders Sinus tachycardia	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Ear and labyrinth disorders Ear and labyrinth disorders - Other, specify	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Ear and labyrinth disorders Ear pain	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Ear and labyrinth disorders Hearing impaired	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Ear and labyrinth disorders Vertigo	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Endocrine disorders Hypothyroidism	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Eye disorders Blurred vision	16.7% 9/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Eye disorders Dry eye	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Eye disorders Extraocular muscle paresis	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Eye disorders Eye disorders - Other, specify	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Eye disorders Watering eyes	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Gastrointestinal disorders Abdominal distension	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Gastrointestinal disorders Abdominal pain	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Gastrointestinal disorders Anal hemorrhage	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Gastrointestinal disorders Constipation	38.9% 21/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Gastrointestinal disorders Diarrhea	5.6% 3/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Gastrointestinal disorders Dry mouth	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Gastrointestinal disorders Dyspepsia	5.6% 3/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Gastrointestinal disorders Dysphagia	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Gastrointestinal disorders Esophagitis	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Gastrointestinal disorders Fecal incontinence	5.6% 3/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Gastrointestinal disorders Gastroesophageal reflux disease	7.4% 4/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Gastrointestinal disorders Mucositis oral	5.6% 3/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Gastrointestinal disorders Nausea	25.9% 14/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Gastrointestinal disorders Oral pain	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Gastrointestinal disorders Vomiting	11.1% 6/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
General disorders Chills	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
General disorders Edema limbs	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
General disorders Fatigue	57.4% 31/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
General disorders Fever	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
General disorders Gait disturbance	27.8% 15/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
General disorders Infusion site extravasation	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
General disorders Irritability	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
General disorders Localized edema	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
General disorders Malaise	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
General disorders Pain	11.1% 6/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
General disorders Sudden death NOS	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Immune system disorders Immune system disorders - Other, specify	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Infections and infestations Infections and infestations - Other, specify	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Infections and infestations Meningitis	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Infections and infestations Peripheral nerve infection	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Infections and infestations Sinusitis	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Infections and infestations Tooth infection	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Infections and infestations Upper respiratory infection	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Infections and infestations Urinary tract infection	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Injury, poisoning and procedural complications Bruising	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Injury, poisoning and procedural complications Dermatitis radiation	13.0% 7/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Injury, poisoning and procedural complications Fall	5.6% 3/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Injury, poisoning and procedural complications Fracture	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Injury, poisoning and procedural complications Wound dehiscence	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Investigations Alanine aminotransferase increased	7.4% 4/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Investigations Alkaline phosphatase increased	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Investigations Aspartate aminotransferase increased	11.1% 6/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Investigations Blood bilirubin increased	5.6% 3/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Investigations Cholesterol high	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Investigations Creatinine increased	5.6% 3/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Investigations INR increased	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Investigations Investigations - Other, specify	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Investigations Lymphocyte count decreased	50.0% 27/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Investigations Lymphocyte count increased	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Investigations Neutrophil count decreased	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Investigations Platelet count decreased	37.0% 20/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Investigations Urine output decreased	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Investigations Weight gain	5.6% 3/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Investigations Weight loss	18.5% 10/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Investigations White blood cell decreased	18.5% 10/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Metabolism and nutrition disorders Anorexia	20.4% 11/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Metabolism and nutrition disorders Dehydration	9.3% 5/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Metabolism and nutrition disorders Hyperglycemia	25.9% 14/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Metabolism and nutrition disorders Hyperkalemia	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Metabolism and nutrition disorders Hypertriglyceridemia	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Metabolism and nutrition disorders Hypoalbuminemia	14.8% 8/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Metabolism and nutrition disorders Hypocalcemia	14.8% 8/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Metabolism and nutrition disorders Hypoglycemia	5.6% 3/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Metabolism and nutrition disorders Hypokalemia	9.3% 5/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Metabolism and nutrition disorders Hypomagnesemia	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Metabolism and nutrition disorders Hyponatremia	7.4% 4/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 3/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Musculoskeletal and connective tissue disorders Back pain	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Musculoskeletal and connective tissue disorders Joint range of motion decreased cervical spine	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	13.0% 7/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	5.6% 3/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Musculoskeletal and connective tissue disorders Muscle weakness right-sided	13.0% 7/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Musculoskeletal and connective tissue disorders Myalgia	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Musculoskeletal and connective tissue disorders Pain in extremity	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	7.4% 4/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Akathisia	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Amnesia	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Ataxia	14.8% 8/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Cognitive disturbance	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Dizziness	9.3% 5/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Dysarthria	5.6% 3/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Dysgeusia	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Dysphasia	24.1% 13/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Edema cerebral	13.0% 7/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Encephalopathy	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Facial nerve disorder	11.1% 6/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Headache	37.0% 20/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Hypersomnia	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Lethargy	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Memory impairment	20.4% 11/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Movements involuntary	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Nervous system disorders - Other, specify	16.7% 9/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Paresthesia	9.3% 5/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Peripheral sensory neuropathy	7.4% 4/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Presyncope	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Pyramidal tract syndrome	13.0% 7/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Seizure	37.0% 20/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Somnolence	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Stroke	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Nervous system disorders Tremor	9.3% 5/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Psychiatric disorders Anxiety	24.1% 13/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Psychiatric disorders Confusion	16.7% 9/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Psychiatric disorders Depression	24.1% 13/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Psychiatric disorders Hallucinations	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Psychiatric disorders Insomnia	18.5% 10/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Psychiatric disorders Personality change	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Psychiatric disorders Psychiatric disorders - Other, specify	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Psychiatric disorders Psychosis	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Renal and urinary disorders Chronic kidney disease	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Renal and urinary disorders Hematuria	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Renal and urinary disorders Proteinuria	11.1% 6/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Renal and urinary disorders Renal and urinary disorders - Other, specify	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Renal and urinary disorders Urinary frequency	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Renal and urinary disorders Urinary incontinence	13.0% 7/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Renal and urinary disorders Urinary retention	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Renal and urinary disorders Urinary tract pain	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Renal and urinary disorders Urinary urgency	5.6% 3/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	7.4% 4/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Respiratory, thoracic and mediastinal disorders Aspiration	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Respiratory, thoracic and mediastinal disorders Cough	7.4% 4/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.6% 3/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Respiratory, thoracic and mediastinal disorders Nasal congestion	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Respiratory, thoracic and mediastinal disorders Postnasal drip	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Respiratory, thoracic and mediastinal disorders Sneezing	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Respiratory, thoracic and mediastinal disorders Sore throat	5.6% 3/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Skin and subcutaneous tissue disorders Alopecia	29.6% 16/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Skin and subcutaneous tissue disorders Nail loss	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Skin and subcutaneous tissue disorders Pruritus	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Skin and subcutaneous tissue disorders Purpura	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Skin and subcutaneous tissue disorders Rash acneiform	3.7% 2/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.6% 3/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Skin and subcutaneous tissue disorders Urticaria	1.9% 1/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Vascular disorders Hypertension	37.0% 20/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.
Vascular disorders Thromboembolic event	7.4% 4/54 • Adverse events were collected from the first day of treatment until 30 days after the last treatment on study for up to approximately 67 weeks for any patient. Concurrent therapy was 5 weeks in length followed by 2 weeks recovery and then adjuvant therapy where 1 cycle = 8 weeks and range of cycles completed 0-7.

Additional Information

Karan Dixit, MD

Northwestern University

Phone: 312-695-1301

Email: karan.dixit@northwestern.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place