Trial Outcomes & Findings for A Phase 2 Evaluation of TRC105 In Combination With Bevacizumab in Patients With Glioblastoma (NCT NCT01564914)

Last Updated: 2019-06-12

Results Overview

Overall survival assessed by determination from time of informed consent on trial to the date of death of each patient enrolled in the trial

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

6 Months

Results posted on

2019-06-12

Participant Flow

Patients were screened and enrolled at 4 sites

Participant milestones

Participant milestones
Measure	Carotuximab (TRC105), Bevacizumab Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle Bevacizumab: IV 10 mg/kg every 2 weeks	Carotuximab (TRC105) Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle
Overall Study STARTED	16	6
Overall Study COMPLETED	16	6
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase 2 Evaluation of TRC105 In Combination With Bevacizumab in Patients With Glioblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TRC105, Bevacizumab n=16 Participants Single arm study TRC105: 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle Bevacizumab: IV 10 mg/kg every 2 weeks	TRC105 n=6 Participants Single arm TRC105: 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle	Total n=22 Participants Total of all reporting groups
Age, Customized Age	64.5 years n=5 Participants	56.5 years n=7 Participants	62 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	3 Participants n=7 Participants	16 Participants n=5 Participants
Screening Karnofsky Score Score = 60: requires occasional assistance	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Screening Karnofsky Score Score = 70: Can care for self; not normal activity	4 participants n=5 Participants	0 participants n=7 Participants	4 participants n=5 Participants
Screening Karnofsky Score Score = 80: Normal activity with effort	8 participants n=5 Participants	2 participants n=7 Participants	10 participants n=5 Participants
Screening Karnofsky Score Score = 90: Normal activities, minor symptoms.	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants
Cancer Histology Glioblastoma	15 Participants n=5 Participants	5 Participants n=7 Participants	20 Participants n=5 Participants
Cancer Histology Giant Cell Glioblastoma	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Cancer Histology Astrocytoma	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Number of Prior Regimens	2.5 prior regimens n=5 Participants	3 prior regimens n=7 Participants	3 prior regimens n=5 Participants

PRIMARY outcome

Timeframe: 6 Months

Population: Patients treated with TRC105 and bevacizumab who expired. Overall survival was not captured in the monotherapy portion of the study.

Overall survival assessed by determination from time of informed consent on trial to the date of death of each patient enrolled in the trial

Outcome measures

Outcome measures
Measure	Carotuximab (TRC105), Bevacizumab n=1 Participants Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle Bevacizumab: IV 10 mg/kg every 2 weeks	Carotuximab (TRC105) Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle
Median Overall Survival (OS)	5.75 months Interval 4.21 to 9.86	—

SECONDARY outcome

Timeframe: Patients are scanned every 8 weeks for approximately 6 months

Population: Patients with at least 1 on study scan were included in the efficacy population. The number of months that patients remained progression free was calculated for 5 evaluable monotherapy patients and 14 evaluable combination therapy patients.

The median number of months that patients remained progression free was calculated using modified RANO criteria to determine progression. Modified RANO criteria is defined as follows: The largest cross-sectional area on the T1-weighted contrast-enhanced images was selected and measured in 2 dimensions with linear measures on the baseline MRI axial sequence. In addition, the largest cross-sectional area of a contiguous hyperintense lesion on FLAIR sequences was measured on the baseline MRI axial sequence. All subsequent scans were compared against these baseline measures (for both CE and FLAIR). New foci of FLAIR signal abnormality were recorded on each subsequent evaluation. Response was scored.

Outcome measures

Outcome measures
Measure	Carotuximab (TRC105), Bevacizumab n=14 Participants Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle Bevacizumab: IV 10 mg/kg every 2 weeks	Carotuximab (TRC105) n=5 Participants Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle
Median Duration That Patients Remained Progression Free on Study	1.81 months Interval 1.25 to 2.07	1.38 months Interval 1.25 to 2.07

SECONDARY outcome

Timeframe: Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, an average of 4 months

Population: Patients who received at least a portion of a dose of TRC105 and/or Bevacizumab

Adverse event frequency per patient according to CTCAE version 4.0.

Outcome measures

Outcome measures
Measure	Carotuximab (TRC105), Bevacizumab n=16 Participants Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle Bevacizumab: IV 10 mg/kg every 2 weeks	Carotuximab (TRC105) n=6 Participants Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle
Number of Participants With Adverse Events Total SAEs	6 Participants	3 Participants
Number of Participants With Adverse Events TRC105 Related SAEs	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Patients are scanned every 8 weeks

Population: Nineteen patients had measurable disease at baseline and received at least one follow up scan and were evaluable for the secondary efficacy outcome measure of PFS by modified RANO criteria. None of the patients treated on this study had a reduction in tumor burden compared to baseline.

Number of patients who respond to study treatment according to modified RANO criteria was calculated (Objective Response Rate (ORR)). Modified RANO criteria is defined as follows: The largest cross-sectional area on the T1-weighted contrast-enhanced images was selected and measured in 2 dimensions with linear measures on the baseline MRI axial sequence. In addition, the largest cross-sectional area of a contiguous hyperintense lesion on FLAIR sequences was measured on the baseline MRI axial sequence. All subsequent scans were compared against these baseline measures (for both CE and FLAIR). New foci of FLAIR signal abnormality were recorded on each subsequent evaluation. Response was scored.

Outcome measures

Outcome measures
Measure	Carotuximab (TRC105), Bevacizumab n=16 Participants Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle Bevacizumab: IV 10 mg/kg every 2 weeks	Carotuximab (TRC105) n=6 Participants Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle
Number of Patients Who Respond to Study Treatment According to Modified RANO Criteria (Objective Response Rate (ORR)).	0 Participants	0 Participants

Adverse Events

Carotuximab (TRC105), Bevacizumab

Serious events: 6 serious events

Other events: 16 other events

Deaths: 1 deaths

Carotuximab (TRC105)

Serious events: 3 serious events

Other events: 6 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Carotuximab (TRC105), Bevacizumab n=16 participants at risk Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle Bevacizumab: IV 10 mg/kg every 2 weeks	Carotuximab (TRC105) n=6 participants at risk Single arm study Carotuximab (TRC105): 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle
Blood and lymphatic system disorders Anemia	6.2% 1/16 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).	0.00% 0/6 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).
General disorders Disease Progression	6.2% 1/16 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).	16.7% 1/6 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).
General disorders Peripheral Oedema	6.2% 1/16 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).	0.00% 0/6 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).
Infections and infestations Periorbital Cellulitis	6.2% 1/16 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).	0.00% 0/6 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).
Nervous system disorders Aphasia	6.2% 1/16 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).	0.00% 0/6 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).
Nervous system disorders Cognitive Disorder	0.00% 0/16 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).	16.7% 1/6 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).
Nervous system disorders Convulsion	6.2% 1/16 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).	33.3% 2/6 • Number of events 2 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).
Nervous system disorders Mental Impairment	6.2% 1/16 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).	0.00% 0/6 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).
Nervous system disorders Transient Ischemic Attack	6.2% 1/16 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).	0.00% 0/6 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).
Respiratory, thoracic and mediastinal disorders Cough	6.2% 1/16 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).	0.00% 0/6 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).
Respiratory, thoracic and mediastinal disorders Hypoxia	6.2% 1/16 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).	0.00% 0/6 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).
Vascular disorders Embolism	6.2% 1/16 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).	0.00% 0/6 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events (on average 4 months).

Other adverse events

Additional Information

Medical Monitor

TRACON Pharmaceuticals

Phone: 8585500780

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60