Trial Outcomes & Findings for Temozolomide and Pazopanib Hydrochloride in Treating Patients With Advanced Pancreatic Neuroendocrine Tumors That Cannot Be Removed By Surgery (NCT NCT01465659)

Last Updated: 2021-08-05

Results Overview

MTD and recommended phase II dose (RP2D) determination for the combination of temozolomide in combination with 400mg pazopanib in patients with advanced PNET will be achieved using a standard "3+3" dose escalation/de-escalation design. After each 3 patients are enrolled into the study, further enrollment will be temporarily suspended until safety has been reviewed for the first 28 days of treatment to determine if dose limiting toxicities have been experienced by patients and if a further 3 patients should be enrolled at the current dose or dose escalation/de-escalation for the next 3 patients should occur.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

29 participants

Primary outcome timeframe

After 28 days (1 cycle of treatment)

Results posted on

2021-08-05

Participant Flow

The study was opened to enrollment on November 15th 2011 with the first patient starting treatment December 12th 2011. The study was designed to enroll up to 40 patients with a phase I dose escalation portion and a phase II expansion portion at the determined dose. The study was closed to further enrollment February 27 2019.

Participant milestones

Participant milestones
Measure	Cohort 1 - Temozolomide 150 mg/m2 and Pazopanib 400 mg Temozolomide 150 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -1 -Temozolomide 100 mg/m2 and Pazopanib 400 mg Temozolomide 100 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -2 - Temozolomide 75 mg/m2 and Pazopanib 400 mg Temozolomide 75 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Phase II -Temozolomide 75 mg/m2 and Pazopanib 400 mg Temozolomide 75mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO
Completed 1 Cycle of Treatment STARTED	7	5	6	11
Completed 1 Cycle of Treatment Completed 1 Cycle of Treatment	7	4	6	11
Completed 1 Cycle of Treatment COMPLETED	7	4	6	10
Completed 1 Cycle of Treatment NOT COMPLETED	0	1	0	1
Completed 2 Cycles/Reached 1st Response STARTED	7	4	6	10
Completed 2 Cycles/Reached 1st Response Attempted 2 Cycles of Treatment	7	4	6	10
Completed 2 Cycles/Reached 1st Response Reached 1st Response	7	4	6	10
Completed 2 Cycles/Reached 1st Response Assessed to Move on to Next Cycle	7	4	4	10
Completed 2 Cycles/Reached 1st Response COMPLETED	5	4	4	9
Completed 2 Cycles/Reached 1st Response NOT COMPLETED	2	0	2	1
Went on to Cycle 3 and Beyond STARTED	5	4	4	9
Went on to Cycle 3 and Beyond COMPLETED	5	4	4	9
Went on to Cycle 3 and Beyond NOT COMPLETED	0	0	0	0
Completed Follow for 1 Year STARTED	7	4	6	11
Completed Follow for 1 Year COMPLETED	1	1	4	7
Completed Follow for 1 Year NOT COMPLETED	6	3	2	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 - Temozolomide 150 mg/m2 and Pazopanib 400 mg Temozolomide 150 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -1 -Temozolomide 100 mg/m2 and Pazopanib 400 mg Temozolomide 100 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -2 - Temozolomide 75 mg/m2 and Pazopanib 400 mg Temozolomide 75 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Phase II -Temozolomide 75 mg/m2 and Pazopanib 400 mg Temozolomide 75mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO
Completed 1 Cycle of Treatment Death	0	1	0	0
Completed 1 Cycle of Treatment Adverse Event	0	0	0	1
Completed 2 Cycles/Reached 1st Response Progressive Disease	1	0	1	1
Completed 2 Cycles/Reached 1st Response Adverse Event	1	0	1	0
Completed Follow for 1 Year Death	6	3	2	4

Baseline Characteristics

Temozolomide and Pazopanib Hydrochloride in Treating Patients With Advanced Pancreatic Neuroendocrine Tumors That Cannot Be Removed By Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 - Temozolomide 150 mg/m2 and Pazopanib 400 mg n=7 Participants Temozolomide 150 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -1 -Temozolomide 100 mg/m2 and Pazopanib 400 mg n=5 Participants Temozolomide 100 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -2 - Temozolomide 75 mg/m2 and Pazopanib 400 mg n=6 Participants Temozolomide 75 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Phase II -Temozolomide 75 mg/m2 and Pazopanib 400 mg n=11 Participants Temozolomide 75mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Total n=29 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=93 Participants	3 Participants n=4 Participants	6 Participants n=27 Participants	9 Participants n=483 Participants	25 Participants n=36 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	2 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants	4 Participants n=36 Participants
Sex: Female, Male Female	3 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants	6 Participants n=483 Participants	13 Participants n=36 Participants
Sex: Female, Male Male	4 Participants n=93 Participants	3 Participants n=4 Participants	4 Participants n=27 Participants	5 Participants n=483 Participants	16 Participants n=36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	2 Participants n=36 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=93 Participants	5 Participants n=4 Participants	6 Participants n=27 Participants	9 Participants n=483 Participants	26 Participants n=36 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants
Race (NIH/OMB) White	6 Participants n=93 Participants	5 Participants n=4 Participants	6 Participants n=27 Participants	10 Participants n=483 Participants	27 Participants n=36 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Region of Enrollment United States	7 participants n=93 Participants	5 participants n=4 Participants	6 participants n=27 Participants	11 participants n=483 Participants	29 participants n=36 Participants

PRIMARY outcome

Timeframe: After 28 days (1 cycle of treatment)

Population: 1 patient in Cohort -1 was not evaluable for this endpoint due to inability to absorb oral medications secondary to bowel edema

Outcome measures

Outcome measures
Measure	Cohort 1/Cohort -1/Cohort -2 - Temozolomide and Pazopanib n=17 Participants Temozolomide 75 - 150 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -1 -Temozolomide 100 mg/m2 and Pazopanib 400 mg Temozolomide 100 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -2 - Temozolomide 75 mg/m2 and Pazopanib 400 mg Temozolomide 75 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Phase II -Temozolomide 75 mg/m2 and Pazopanib 400 mg Temozolomide 75mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO
Determine the Maximum Tolerated Dose (MTD) of Temozolomide in Combination With 400 mg Pazopanib in Patients With Advanced Pancreatic Neuroendocrine Tumor (PNET) in Phase I	75 mg/m2	—	—	—

PRIMARY outcome

Timeframe: After two cycles of treatment (8 weeks)

Population: 1 patient was determined not to be evaluable for response in phase II

Overall response rate will be determined by the number of patients who's best response as assessed by RECIST 1.1 is complete response (CR) and partial response (PR) in patients with PNET that are enrolled at the recommended phase II dose (RP2D) (PK cohort included). CR= Disappearance of all target lesions PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Cohort 1/Cohort -1/Cohort -2 - Temozolomide and Pazopanib n=10 Participants Temozolomide 75 - 150 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -1 -Temozolomide 100 mg/m2 and Pazopanib 400 mg Temozolomide 100 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -2 - Temozolomide 75 mg/m2 and Pazopanib 400 mg Temozolomide 75 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Phase II -Temozolomide 75 mg/m2 and Pazopanib 400 mg Temozolomide 75mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO
Overall Response Rate (ORR) in Patients With Advanced Neuroendocrine Tumors (PNET) Treated With Temozolomide and Pazopanib Combination Treatment at the RP2D in Phase II	0 Participants	—	—	—

SECONDARY outcome

Timeframe: During treatment and up to one month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days.

Safety and toxicity will be reported in the number of patients who experience adverse events during treatment, graded using CTCAE 4.03. In general the severity of an AE is graded as follows: Mild (grade 1): the event causes discomfort without disruption of normal daily activities. Moderate (grade 2): the event causes discomfort that affects normal daily activities. Severe (grade 3): the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical status. Life-threatening (grade 4): the patient was at risk of death at the time of the event. Fatal (grade 5): the event caused death.

Outcome measures

Outcome measures
Measure	Cohort 1/Cohort -1/Cohort -2 - Temozolomide and Pazopanib n=7 Participants Temozolomide 75 - 150 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -1 -Temozolomide 100 mg/m2 and Pazopanib 400 mg n=5 Participants Temozolomide 100 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -2 - Temozolomide 75 mg/m2 and Pazopanib 400 mg n=6 Participants Temozolomide 75 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Phase II -Temozolomide 75 mg/m2 and Pazopanib 400 mg n=11 Participants Temozolomide 75mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO
Number of Patients Who Experience Toxicity Events Undergoing This Treatment. Any AE	7 patients	5 patients	6 patients	11 patients
Number of Patients Who Experience Toxicity Events Undergoing This Treatment. AE related to treatment	7 patients	5 patients	6 patients	11 patients
Number of Patients Who Experience Toxicity Events Undergoing This Treatment. SAE	3 patients	3 patients	1 patients	1 patients
Number of Patients Who Experience Toxicity Events Undergoing This Treatment. SAE related to treatment	3 patients	1 patients	1 patients	1 patients
Number of Patients Who Experience Toxicity Events Undergoing This Treatment. Grade 5 SAE	0 patients	1 patients	0 patients	0 patients
Number of Patients Who Experience Toxicity Events Undergoing This Treatment. Came off treatment due to an AE	3 patients	3 patients	3 patients	2 patients

SECONDARY outcome

Timeframe: Multiple timepoints during Days 1-3 of cycle 1 and cycle 2 (1 cycle =28 days)

Population: Data that was collected but not analyzed. The data that was collected is reported below for each patient at each timepoint.

For the Six Patients in Phase I portion who are enrolled in the PK cohort: Blood will be drawn on Day 1 before beginning treatment and again at 10 minutes, 30 minutes, 1, 2, 3, 4, 6 and 8 hours after beginning treatment. On Day 2- 24 hours after the first dose from Day 1, and again 10 minutes, 30 minutes, 1, 2, 3, 4, 6 and 8 hours after taking the second dose. Day 3 - 24 hours after the second dose from Day 2. Cycle 1 Day 1 only temozolomide will be taken by the patient and on Cycle 2 Day 2, temozolomide and pazopanib will be taken by the patient. Data that was collected but not analyzed. The data that was collected is reported below in raw form.

Outcome measures

Outcome measures
Measure	Cohort 1/Cohort -1/Cohort -2 - Temozolomide and Pazopanib n=6 Participants Temozolomide 75 - 150 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -1 -Temozolomide 100 mg/m2 and Pazopanib 400 mg Temozolomide 100 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -2 - Temozolomide 75 mg/m2 and Pazopanib 400 mg Temozolomide 75 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Phase II -Temozolomide 75 mg/m2 and Pazopanib 400 mg Temozolomide 75mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 2 Day 1 at time 0.17 hours	0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 1 Day 1 at time 3 hours	2024 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 2 Day 1 at time 4 hours	1586 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 1 Day 1 at time 0 hours	0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 1 Day 1 at time 0.17 hours	0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 1 Day 1 at time 0.5 hours	91.8 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 1 Day 1 at time 1 hours	425.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 1 Day 1 at time 2 hours	462 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 1 Day 1 at time 3 hours	583 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 1 Day 1 at time 4 hours	210.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 1 Day 1 at time 6 hours	105 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 1 Day 1 at time 8 hours	44 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 1 Day 1 at time 24 hours	0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 2 Day 1 at time 0 hours	0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 2 Day 1 at time 0.5 hours	25.2 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 2 Day 1 at time 1 hours	90.8 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 2 Day 1 at time 2 hours	516.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 2 Day 1 at time 3 hours	255 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 2 Day 1 at time 4 hours	519 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 2 Day 1 at time 6 hours	154 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 2 Day 1 at time 8 hours	99.9 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #1 : Cycle 2 Day 1 at time 24 hours	0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 1 Day 1 at time 0 hours	0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 1 Day 1 at time 0.17 hours	0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 1 Day 1 at time 0.5 hours	54.9 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 1 Day 1 at time 1 hours	494 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 1 Day 1 at time 2 hours	660.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 1 Day 1 at time 3 hours	557.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 1 Day 1 at time 4 hours	99 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 1 Day 1 at time 6 hours	105.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 1 Day 1 at time 8 hours	109.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 1 Day 1 at time 24 hours	0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 2 Day 1 at time 0 hours	0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 2 Day 1 at time 0.17 hours	0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 2 Day 1 at time 0.5 hours	41.6 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 2 Day 1 at time 1 hours	115 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 2 Day 1 at time 2 hours	1490 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 2 Day 1 at time 3 hours	961.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 2 Day 1 at time 4 hours	382.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 2 Day 1 at time 6 hours	510.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 2 Day 1 at time 8 hours	109.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #2 : Cycle 2 Day 1 at time 24 hours	0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 1 Day 1 at time 0 hours	0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 1 Day 1 at time 0.17 hours	0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 1 Day 1 at time 0.5 hours	527 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 1 Day 1 at time 1 hours	1670 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 1 Day 1 at time 2 hours	2440 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 1 Day 1 at time 4 hours	1466 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 1 Day 1 at time 6 hours	718 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 1 Day 1 at time 8 hours	317 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 1 Day 1 at time 24 hours	4.3 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 2 Day 1 at time 0 hours	4.1 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 2 Day 1 at time 0.17 hours	241 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 2 Day 1 at time 0.5 hours	909 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 2 Day 1 at time 1 hours	2130 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 2 Day 1 at time 2 hours	2490 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 2 Day 1 at time 3 hours	1933 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 2 Day 1 at time 6 hours	761 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 2 Day 1 at time 8 hours	328 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #3 : Cycle 2 Day 1 at time 24 hours	4.75 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 1 Day 1 at time 0 hours	0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 1 Day 1 at time 0.17 hours	3.6 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 1 Day 1 at time 0.5 hours	492 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 1 Day 1 at time 1 hours	3025 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 1 Day 1 at time 2 hours	2805 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 1 Day 1 at time 3 hours	1765 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 1 Day 1 at time 4 hours	1430 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 1 Day 1 at time 6 hours	686.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 1 Day 1 at time 8 hours	383 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 1 Day 1 at time 24 hours	1.2 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 2 Day 1 at time 0 hours	2.4 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 2 Day 1 at time 0.17 hours	2.3 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 2 Day 1 at time 0.5 hours	3.0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 2 Day 1 at time 1 hours	1.6 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 2 Day 1 at time 2 hours	1.0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 2 Day 1 at time 3 hours	12 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 2 Day 1 at time 4 hours	3360 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 2 Day 1 at time 6 hours	2610 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 2 Day 1 at time 8 hours	1225 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #4 : Cycle 2 Day 1 at time 24 hours	3285 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 1 Day 1 at time 0 hours	0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 1 Day 1 at time 0.17 hours	19.1 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 1 Day 1 at time 0.5 hours	177 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 1 Day 1 at time 1 hours	227 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 1 Day 1 at time 2 hours	275 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 1 Day 1 at time 3 hours	829.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 1 Day 1 at time 4 hours	925 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 1 Day 1 at time 6 hours	1145 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 1 Day 1 at time 8 hours	819.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 1 Day 1 at time 24 hours	44.2 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 2 Day 1 at time 0 hours	0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 2 Day 1 at time 0.17 hours	108 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 2 Day 1 at time 0.5 hours	166.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 2 Day 1 at time 1 hours	188.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 2 Day 1 at time 2 hours	422.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 2 Day 1 at time 3 hours	716.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 2 Day 1 at time 4 hours	1070 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 2 Day 1 at time 6 hours	1180 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 2 Day 1 at time 8 hours	744.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #5 : Cycle 2 Day 1 at time 24 hours	36.7 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 1 Day 1 at time 0 hours	0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 1 Day 1 at time 0.17 hours	459.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 1 Day 1 at time 0.5 hours	3055 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 1 Day 1 at time 1 hours	2720 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 1 Day 1 at time 2 hours	1735 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 1 Day 1 at time 3 hours	1470 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 1 Day 1 at time 4 hours	1195 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 1 Day 1 at time 6 hours	499.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 1 Day 1 at time 8 hours	251 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 1 Day 1 at time 24 hours	1.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 2 Day 1 at time 0 hours	0 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 2 Day 1 at time 0.17 hours	67.7 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 2 Day 1 at time 0.5 hours	4095 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 2 Day 1 at time 1 hours	2135 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 2 Day 1 at time 2 hours	2095 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 2 Day 1 at time 3 hours	1445 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 2 Day 1 at time 4 hours	1025.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 2 Day 1 at time 6 hours	324.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 2 Day 1 at time 8 hours	192.5 ng/mL	—	—	—
Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration Patient #6a : Cycle 2 Day 1 at time 24 hours	1.3 ng/mL	—	—	—

SECONDARY outcome

Timeframe: Baseline and after every 2 cycles of treatment (8 weeks) for up to 40 months

Population: The study did not reach its anticipated sample size and anticipated endpoints for phase II. Due to this and relatively small number of patients it was determined by the PI to have no merit or statistical significance to calculate PFS per dose cohort and dose cohorts were combined to summarize PFS.

PFS will be defined as will be defined as the time from the first study treatment to the first occurrence of progression or death. Progressive disease will be assessed using RECIST v1.1 criteria where in general the following definition is true: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum recorded on study AND an absolute increase in the sum of at least 5 mm OR the appearance of one or more new lesions

Outcome measures

Outcome measures
Measure	Cohort 1/Cohort -1/Cohort -2 - Temozolomide and Pazopanib n=29 Participants Temozolomide 75 - 150 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -1 -Temozolomide 100 mg/m2 and Pazopanib 400 mg Temozolomide 100 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -2 - Temozolomide 75 mg/m2 and Pazopanib 400 mg Temozolomide 75 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Phase II -Temozolomide 75 mg/m2 and Pazopanib 400 mg Temozolomide 75mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO
Progression Free Survival (PFS)	9.38 months Interval 6.18 to 13.3	—	—	—

SECONDARY outcome

Timeframe: Baseline and after every 2 cycles of treatment (8 weeks) and up to 60 months

Population: The study did not reach its anticipated sample size and anticipated endpoints for phase II. Due to this and relatively small number of patients it was determined by the PI to have no merit or statistical significance to calculate OS per dose cohort and dose cohorts were combined to summarize OS.

OS is defined as the time from first study treatment until death from any cause.

Outcome measures

Outcome measures
Measure	Cohort 1/Cohort -1/Cohort -2 - Temozolomide and Pazopanib n=29 Participants Temozolomide 75 - 150 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -1 -Temozolomide 100 mg/m2 and Pazopanib 400 mg Temozolomide 100 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -2 - Temozolomide 75 mg/m2 and Pazopanib 400 mg Temozolomide 75 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Phase II -Temozolomide 75 mg/m2 and Pazopanib 400 mg Temozolomide 75mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO
Overall Survival (OS)	24.2 months Interval 18.3 to Upper limit was not reached	—	—	—

SECONDARY outcome

Timeframe: After every 2 courses of treatment (8 weeks) for up to 41 cycles where 1 cycle =28 days.

Population: The study did not reach its anticipated sample size and anticipated endpoints for phase II. Due to this and relatively small number of patients it was determined by the PI to have no merit or statistical significance to calculate DCR per dose cohort and dose cohorts were combined to summarize DCR.

Disease Control Rate (DCR) is defined as the number of patients demonstrating the complete response, partial response or stable disease. In general the following is true: Complete Response (CR) Disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR) At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters Stable Disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of diameters while on study

Outcome measures

Outcome measures
Measure	Cohort 1/Cohort -1/Cohort -2 - Temozolomide and Pazopanib n=29 Participants Temozolomide 75 - 150 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -1 -Temozolomide 100 mg/m2 and Pazopanib 400 mg Temozolomide 100 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -2 - Temozolomide 75 mg/m2 and Pazopanib 400 mg Temozolomide 75 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Phase II -Temozolomide 75 mg/m2 and Pazopanib 400 mg Temozolomide 75mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO
Number of Patients Experiencing Response to Treatment or Stable Disease (Disease Control Rate)	20 Participants	—	—	—

SECONDARY outcome

Timeframe: After every 2 courses of treatment (8 weeks)

Population: Data not collected or analyzed for this outcome measure

Duration of response (DOR) is defined at the time from documented overall response (compete response, partial response, stable disease) until disease progression where the following are true: Complete Response (CR) Disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR) At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters Stable Disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of diameters while on study

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At Baseline and after two corurses of treatment (8 weeks)

For Patients in Phase II Portion: Patients will have a perfusion functional computed tomography (fCT) scan at baseline and after two courses of treatment.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and at Response assessment after two courses of treatment (8 weeks)

For Patients in Phase II Portion: The level of expression of tissue methyl-guanine methytransferase (MGMT)will be measured in tissue from the diagnostic biopsy and these results will be correlated with response rate.

Outcome measures

Outcome data not reported

Adverse Events

Cohort 1 - Temozolomide 150 mg/m2 and Pazopanib 400 mg

Serious events: 3 serious events

Other events: 7 other events

Deaths: 6 deaths

Cohort -1 -Temozolomide 100 mg/m2 and Pazopanib 400 mg

Serious events: 3 serious events

Other events: 5 other events

Deaths: 4 deaths

Cohort -2 - Temozolomide 75 mg/m2 and Pazopanib 400 mg

Serious events: 1 serious events

Other events: 6 other events

Deaths: 2 deaths

Phase II -Temozolomide 75 mg/m2 and Pazopanib 400 mg

Serious events: 1 serious events

Other events: 17 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1 - Temozolomide 150 mg/m2 and Pazopanib 400 mg n=7 participants at risk Temozolomide 150 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -1 -Temozolomide 100 mg/m2 and Pazopanib 400 mg n=5 participants at risk Temozolomide 100 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Cohort -2 - Temozolomide 75 mg/m2 and Pazopanib 400 mg n=6 participants at risk Temozolomide 75 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO	Phase II -Temozolomide 75 mg/m2 and Pazopanib 400 mg n=17 participants at risk；n=11 participants at risk Temozolomide 75mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28 temozolomide: Given PO pazopanib hydrochloride: Given PO
Gastrointestinal disorders Upper Gastrointestinal hemorrhage	0.00% 0/7 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/5 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/6 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	9.1% 1/11 • Number of events 1 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.
Infections and infestations Shingles	14.3% 1/7 • Number of events 1 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/5 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/6 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/11 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.
General disorders Guillian-Barre Syndrome	14.3% 1/7 • Number of events 1 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/5 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/6 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/11 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) ACTH secreting tumor with cushings syndrome	0.00% 0/7 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	20.0% 1/5 • Number of events 2 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/6 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/11 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.
Investigations AST and ALT increased	0.00% 0/7 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	20.0% 1/5 • Number of events 1 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	16.7% 1/6 • Number of events 1 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/11 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.
Investigations Thrombocytopenia	14.3% 1/7 • Number of events 1 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/5 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/6 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/11 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.
Respiratory, thoracic and mediastinal disorders Epistasis	14.3% 1/7 • Number of events 1 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/5 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/6 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/11 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.
Blood and lymphatic system disorders Splenic hemorrage	14.3% 1/7 • Number of events 1 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/5 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/6 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/11 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.
Metabolism and nutrition disorders Protein calorie malnutrition	0.00% 0/7 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	20.0% 1/5 • Number of events 1 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/6 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.	0.00% 0/11 • Patients were monitored for adverse events for the duration of treatment and up to 1 month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days This contains data that has been collected and reported in the eCRFs on April 22nd 2020 and may be updated at the time of secondary outcome measure reporting. Due to the way that adverse events and serious adverse events are collect and reported in the eCRFs the "other" adverse events may contain some serious adverse event data.

Other adverse events

Additional Information

Sheetal Kircher, MD

Northwestern University

Phone: 312-695-0990

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place