A Phase 1B Dose-escalation and Phase 2a Study of Carotuximab (TRC105) in Combination With Pazopanib in Patients With Advanced Soft Tissue Sarcoma

NCT01975519 | Completed Phase 1 Results

• 1 other identifier: 105SAR101
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Advanced Soft Tissue Sarcoma

Keywords

TRC105; CD105; Endoglin; Angiogenesis Inhibitor; STS; Soft Tissue Sarcoma; TKI; Tyrosine Kinase Inhibitor; Pazopanib; Votrient; Advanced Soft Tissue Sarcoma; Angiosarcoma

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose Limiting Toxicity (DLT)

  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.

  56 days

• Progression Free Survival of Patients With Advanced Soft Tissue Sarcoma (Phase 1 and 2)

  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

  from screening to either disease progression or death

• Objective Response Rate in a Cohort of Patients With Angiosarcoma

  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

  1.5 years

Secondary Outcomes (5)

• Trough Concentrations of TRC105 (Phase 2)

  4, 6, 8, and 10 weeks

• Number of Patients With and Without Development of Immunogenicity Antibodies (Phase 1 and 2)

  32 months

• Number of Patients With and Without Expression of Endoglin on Sarcoma Tissue (Phase 1 and 2)

  12 months

• Objective Response Rate in Patients With Advanced Soft Tissue Sarcoma by RECIST 1.1

  12 months

• Progression Free Survival in a Cohort of Patients With Angiosarcoma (Phase 2)

  26 months

Study Arms (1)

TRC105 and Pazopanib

EXPERIMENTAL

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

Interventions

TRC105 and Pazopanib DRUG

Weekly TRC105 in combination with standard dose Pazopanib.

Also known as: Chimeric Antibody (TRC105) to CD105, Votrient

TRC105 and Pazopanib

Eligibility Criteria

• Age: 12 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed unresectable soft tissue sarcoma that has progressed following treatment with chemotherapy. Prior pazopanib is allowed if the drug was not discontinued for toxicity ( Phase 1b only)
• Histologically confirmed metastatic soft tissue sarcoma that has progressed by RECIST following treatment with anthracycline chemotherapy. Patients may have received up to four lines of systemic therapy for metastatic disease and no more than two lines of combination treatment ( Phase 2 only)
• Histologically confirmed locally advanced (e.g. unresectable) or metastatic angiosarcoma that has progressed following treatment with prior systemic therapy. Progression must be documented on or following the most recent systemic therapy. Prior pazopanib is allowed if the drug was not discontinued for toxicity (Phase 2 angiosarcoma cohorts only)
• Measurable disease by RECIST
• Age of 12 years or older (patient must weigh ≥ 40 kg)
• ECOG performance status ≤ 1
• Resolution of all acute adverse events resulting from prior cancer therapies to NCI CTCAE grade ≤ 1 or baseline (except alopecia or neuropathy)
• Adequate organ function.
• Willingness and ability to consent for self to participate in study
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

You may not qualify if:

• Prior treatment with TRC105
• Prior treatment with a VEGFR TKI (including pazopanib) (Phase 2 only)
• Current treatment on another therapeutic clinical trial
• Receipt of systemic anticancer therapy, including investigational agents, within 28 days of starting study treatment.
• No major surgical procedure or significant traumatic injury within 6 weeks prior to study registration, and must have fully recovered from any such procedure; date of surgery (if applicable) or the anticipated need for a major surgical procedure within the next six months.
• Patients who have received wide field radiotherapy ≤ 28 days or limited field radiation for palliation \< 14 days prior to cycle 1 day 1 or those patients who have not recovered adequately from side effects of such therapy
• Uncontrolled chronic hypertension
• Significant ascites or pericardial or pleural effusion
• History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
• Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, PTCA or CABG within the past 6 months. Deep venous thrombosis within 6 months, unless the patient is anti-coagulated without the use of warfarin for at least 2 weeks. In this situation, low molecular weight heparin is preferred.
• Active bleeding or pathologic condition that carries a high risk of bleeding. Patients who have been uneventfully anti-coagulated with low molecular weight heparin are eligible.
• Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy
• Known active viral or nonviral hepatitis or cirrhosis
• History of hemorrhage or hemoptysis within 3 months of starting study treatment
• History of peptic ulcer within the past 3 months of treatment

Sponsors & Collaborators

• Tracon Pharmaceuticals Inc.: lead

Study Sites (9)

University of Alabama at Birmingham

Birmingham, Alabama, 35243, United States

Location

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 92122, United States

Location

Mount Sinai School of Medicine-Tisch Cancer Institute

New York, New York, 10029, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Mary Crowley Cancer Research Center

Dallas, Texas, 75230, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Sarcoma; Hemangiosarcoma

Interventions

carotuximab; pazopanib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue

Results Point of Contact

• Title: Charles Theuer, Medical Monitor
• Organization: TRACON Pharmaceuticals Inc

ctheuer@traconpharma.com

8585500780

Study Officials

• Charles Theuer, MD

  Tracon Pharmaceuticals Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2013
• First Posted: November 4, 2013
• Study Start: December 10, 2013
• Primary Completion: March 11, 2019
• Study Completion: March 11, 2019
• Last Updated: May 20, 2020
• Results First Posted: May 12, 2020

Record last verified: 2020-05

Locations

US (9)