A Phase 1B Dose-escalation and Phase 2a Study of Carotuximab (TRC105) in Combination With Pazopanib in Patients With Advanced Soft Tissue Sarcoma
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|ClinicalTrials.gov Identifier: NCT01975519|
Recruitment Status : Completed
First Posted : November 3, 2013
Results First Posted : May 12, 2020
Last Update Posted : May 20, 2020
The purpose of the phase 1b portion is to evaluate safety and tolerability and determine a recommended phase 2 dose for TRC105 when added to standard dose pazopanib in patients with advanced soft tissue sarcoma. Up to 30 patients will be treated.
The purpose of the phase 2 portion is to estimate the PFS of patients with advanced soft tissue sarcoma by RECIST 1.1 and estimate ORR in a separate cohort of patients with angiosarcoma by RECIST 1.1. Up to 89 patients will be treated in phase 2, including two cohorts of up to 13 patients with angiosarcoma.
|Condition or disease||Intervention/treatment||Phase|
|Advanced Soft Tissue Sarcoma||Drug: TRC105 and Pazopanib||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||111 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1B Dose-escalation and Phase 2a Study of Carotuximab (TRC105) in Combination With Pazopanib in Patients With Advanced Soft Tissue Sarcoma|
|Actual Study Start Date :||December 10, 2013|
|Actual Primary Completion Date :||March 11, 2019|
|Actual Study Completion Date :||March 11, 2019|
Experimental: TRC105 and Pazopanib
Weekly TRC105 in combination with standard dose pazopanib or every two week administration during cycle 1, and starting on cycle 2 day 1 and beyond, TRC105 may be administered every two weeks. This is also in combination with standard dose pazopanib.
Drug: TRC105 and Pazopanib
Weekly TRC105 in combination with standard dose Pazopanib.
- Number of Participants With Dose Limiting Toxicity (DLT) [ Time Frame: 56 days ]For DLT evaluation, severity (grade) was classified according to common terminology criteria for adverse events version 4.0 (CTCAE v4.0). DLTs were defined as grade 4 neutropenia persisting for ≥ 5 days, febrile neutropenia (grade 4 neutropenia with fever > 38.5 ºC both sustained over a 24 hour period), neutropenic infection (grade ≥ 3 neutropenia with grade ≥ 3 infection), anemia ≥ grade 4, grade > 4 thrombocytopenia or grade ≥ 3 thrombocytopenia and grade ≥ 3 hemorrhage, or grade 3 or 4 nonhematologic toxicity with the following exceptions: nausea, vomiting, or diarrhea for <48 hours, asymptomatic electrolyte abnormalities that are corrected to grade 1 or better in < 72 hours, or headache lasting less than 48 hours.
- Progression Free Survival of Patients With Advanced Soft Tissue Sarcoma (Phase 1 and 2) [ Time Frame: from screening to either disease progression or death ]Number of patients with progression free survival, as defined as time from screening to either first disease progression or death from any cause per RECIST version 1.1
- Objective Response Rate in a Cohort of Patients With Angiosarcoma [ Time Frame: 1.5 years ]The best response according to RECIST 1.1 for each patient in the phase 2 angiosarcoma cohort with measurable disease and who received at least one dose of study drug will be listed by cohort and tumor type
- Trough Concentrations of TRC105 (Phase 2) [ Time Frame: 4, 6, 8, and 10 weeks ]Trough serum TRC105 concentrations will be measured using validated ELISA methods.
- Number of Patients With and Without Development of Immunogenicity Antibodies (Phase 1 and 2) [ Time Frame: 32 months ]Anti-product antibody concentrations will be measured using validated ELISA methods. Anti-product antibody concentrations will be evaluated in the context of pharmacokinetic parameters and AE profiles.
- Number of Patients With and Without Expression of Endoglin on Sarcoma Tissue (Phase 1 and 2) [ Time Frame: 12 months ]Expression will be determined by immunohistochemistry for each patient who received at least one dose of TRC105
- Objective Response Rate in Patients With Advanced Soft Tissue Sarcoma by RECIST 1.1 [ Time Frame: 12 months ]The best response (CR, PR, SD or PD according to RECIST 1.1) for each patient (phase 1 and phase 2) with measurable disease who received at least one dose of TRC105 study drug
- Progression Free Survival in a Cohort of Patients With Angiosarcoma (Phase 2) [ Time Frame: 26 months ]Time from screening to either first disease progression or death from any cause per RECIST version 1.1
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01975519
|United States, Alabama|
|University of Alabama at Birmingham|
|Birmingham, Alabama, United States, 35243|
|United States, California|
|Sarcoma Oncology Center|
|Santa Monica, California, United States, 90403|
|United States, Florida|
|Mayo Clinic Jacksonville|
|Jacksonville, Florida, United States, 32224|
|United States, Minnesota|
|Mayo Clinic Rochester|
|Rochester, Minnesota, United States, 55905|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 92122|
|Mount Sinai School of Medicine-Tisch Cancer Institute|
|New York, New York, United States, 10029|
|United States, North Carolina|
|Durham, North Carolina, United States, 27710|
|United States, Texas|
|Mary Crowley Cancer Research Center|
|Dallas, Texas, United States, 75230|
|United States, Utah|
|University of Utah|
|Salt Lake City, Utah, United States, 84112|
|Study Director:||Charles Theuer, MD||Tracon Pharmaceuticals Inc.|