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 : Active, not recruiting
First Posted : November 4, 2013
Last Update Posted : December 4, 2018
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|
|Study Start Date :||December 2013|
|Estimated Primary Completion Date :||March 2019|
|Estimated Study Completion Date :||March 2020|
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.
- Maximum Tolerated Dose of TRC105 in Combination with Pazopanib (Phase 1b) [ Time Frame: 28 days ]Safety and dose limiting toxicity will be assessed by dose cohort.
- Progression free survival of patients with advanced soft tissue sarcoma (Phase 2) [ Time Frame: 12 months ]By RECIST 1.1
- Objective response rate in a cohort of patients with angiosarcoma (Phase 2) [ Time Frame: 12 months ]By RECIST 1.1
- Response rate (phase 1) [ Time Frame: 12 months ]By RECIST 1.1
- Peak and trough concentrations of TRC105 (phase 1 and 2) [ Time Frame: 8 months ]Peak and trough serum TRC105 concentrations will be measured using validated ELISA methods.
- Development of immunogenicity antibodies (phase 1 and 2) [ Time Frame: 8 months ]Anti-Product Antibody (APA) concentrations will be measured using validated ELISA methods.
- 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
- Concentrations of a panel of angiogenic protein biomarkers in plasma (phase 1 and 2) [ Time Frame: 24 months ]Plasma will be analyzed for biomarkers such as VEGF, VEGF-R2, PIGF, and sCD105
- Objective response rate in patients with advanced soft tissue sarcoma by RECIST 1.1 (phase 2) [ Time Frame: 12 months ]The best response (CR, PR, SD or PD according to RECIST 1.1) for each patient 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: 12 months ]By RECIST 1.1
- Frequency and severity of adverse events (phase 2) [ Time Frame: 1 week ]By NCI CTCAE (Version 4.0)
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.|