- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01975519
A Phase 1B Dose-escalation and Phase 2a Study of Carotuximab (TRC105) in Combination With Pazopanib in Patients With Advanced Soft Tissue Sarcoma
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Alabama
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Birmingham, Alabama, United States, 35243
- University of Alabama at Birmingham
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California
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Santa Monica, California, United States, 90403
- Sarcoma Oncology Center
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Florida
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Jacksonville, Florida, United States, 32224
- Mayo Clinic Jacksonville
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic Rochester
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New York
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Buffalo, New York, United States, 92122
- Roswell Park Cancer Institute
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New York, New York, United States, 10029
- Mount Sinai School of Medicine-Tisch Cancer Institute
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North Carolina
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Durham, North Carolina, United States, 27710
- Duke University
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Texas
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Dallas, Texas, United States, 75230
- Mary Crowley Cancer Research Center
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Utah
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Salt Lake City, Utah, United States, 84112
- University of Utah
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
- Available archival tumor specimen of the soft tissue sarcoma that meets inclusion criterion #1, #2 or #3
Exclusion Criteria:
- 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
- History of gastrointestinal perforation or fistula in the past 6 months, or while previously on antiangiogenic therapy, unless underlying risk has been resolved
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
- Receipt of a strong CYP3A4 inducer within 12 days prior to cycle 1 day 1 or a strong CYP3A4 inhibitor within 7 days prior to cycle 1 day 1.
- Pregnancy or breastfeeding. Female patients must be surgically sterile (i.e.: hysterectomy) or be postmenopausal, or must agree to use effective contraception during the study and for 3 months following last dose of TRC105. All female patients of reproductive potential must have a negative pregnancy test (serum or urine) within 7 days prior to first dose. Male patients must be surgically sterile or must agree to use effective contraception during the study and for 3 months following last dose of TRC105. The definition of effective contraception will be based on the judgment of the Principal Investigator or a designated associate.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for this study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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Weekly TRC105 in combination with standard dose Pazopanib.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Dose Limiting Toxicity (DLT)
Time Frame: 56 days
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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.
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56 days
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Progression Free Survival of Patients With Advanced Soft Tissue Sarcoma (Phase 1 and 2)
Time Frame: from screening to either disease progression or death
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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
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from screening to either disease progression or death
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Objective Response Rate in a Cohort of Patients With Angiosarcoma
Time Frame: 1.5 years
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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
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1.5 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Trough Concentrations of TRC105 (Phase 2)
Time Frame: 4, 6, 8, and 10 weeks
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Trough serum TRC105 concentrations will be measured using validated ELISA methods.
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4, 6, 8, and 10 weeks
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Number of Patients With and Without Development of Immunogenicity Antibodies (Phase 1 and 2)
Time Frame: 32 months
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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.
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32 months
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Number of Patients With and Without Expression of Endoglin on Sarcoma Tissue (Phase 1 and 2)
Time Frame: 12 months
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Expression will be determined by immunohistochemistry for each patient who received at least one dose of TRC105
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12 months
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Objective Response Rate in Patients With Advanced Soft Tissue Sarcoma by RECIST 1.1
Time Frame: 12 months
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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
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12 months
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Progression Free Survival in a Cohort of Patients With Angiosarcoma (Phase 2)
Time Frame: 26 months
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Time from screening to either first disease progression or death from any cause per RECIST version 1.1
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26 months
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 105SAR101
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Advanced Soft Tissue Sarcoma
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University of WashingtonAadi Bioscience, Inc.Active, not recruitingAdvanced Soft Tissue Sarcoma | Metastatic Soft Tissue Sarcoma | Locally Advanced Soft Tissue SarcomaUnited States
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Grupo Espanol de Investigacion en SarcomasRecruitingAdvanced Solid Tumor | Advanced Soft-tissue Sarcoma | Advanced L-sarcomas | Other Advanced Sarcomas | Localized Soft-tissue SarcomaSpain
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National Cancer Institute (NCI)RecruitingMetastatic Alveolar Soft Part Sarcoma | Unresectable Alveolar Soft Part Sarcoma | Advanced Soft Tissue Sarcoma | Advanced Alveolar Soft Part SarcomaUnited States
-
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.TerminatedAdvanced Cancer | Advanced Soft-tissue SarcomaChina
-
Massachusetts General HospitalJazz PharmaceuticalsRecruitingAdvanced Soft-tissue Sarcoma | Metastatic Soft-tissue Sarcoma | Advanced Leiomyosarcoma | Leiomyosarcoma MetastaticUnited States
-
Epizyme, Inc.RecruitingAdvanced Soft-tissue Sarcoma | Advanced Epithelioid SarcomaUnited States, Taiwan, Canada, United Kingdom
-
CytRxUnknownUnresectable Soft Tissue Sarcoma | Metastatic Soft Tissue Sarcoma | Locally Advanced Soft Tissue SarcomaUnited States, Australia, Russian Federation, Hungary, India, Romania, Ukraine
-
Shanghai 6th People's HospitalRecruitingAdvanced or Unresectable Locally Advanced Bone and Soft Tissue SarcomaChina
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Centre Leon BerardNovartis; National Cancer Institute, FranceRecruitingAdvanced Soft-tissue Sarcoma | Metastatic Soft-tissue SarcomaFrance
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UNICANCERRecruitingAdvanced Soft-tissue Sarcoma | Metastatic Soft-tissue SarcomaFrance
Clinical Trials on TRC105 and Pazopanib
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Tracon Pharmaceuticals Inc.CompletedTrial of TRC105 and Pazopanib Versus Pazopanib Alone in Patients With Advanced Angiosarcoma (TAPPAS)Advanced AngiosarcomaUnited States, France, Italy, Austria, Germany, Poland, Spain, United Kingdom
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National Cancer Institute (NCI)CompletedUrothelial Carcinoma | Ureteral Neoplasms | Ureter Cancer | Cancer of the Ureter | Neoplasm, UreteralUnited States
-
National Cancer Institute (NCI)Terminated
-
National Cancer Institute (NCI)CompletedProstate Cancer | Metastatic Castrate Resistant Prostate CancerUnited States
-
Tracon Pharmaceuticals Inc.No longer availableSolid TumorsUnited States
-
Tracon Pharmaceuticals Inc.CompletedFallopian Tube Carcinoma | Primary Peritoneal Carcinoma | Recurrent Ovarian CancerUnited States
-
National Cancer Institute (NCI)CompletedCarcinoma, Hepatocellular | Hepatocellular Carcinoma | Hepatocellular CancerUnited States
-
University of Alabama at BirminghamTracon Pharmaceuticals Inc.Completed
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Tracon Pharmaceuticals Inc.TerminatedRenal Cell CarcinomaUnited States, Hungary, Czechia, United Kingdom
-
Cure HHTUniversity of North CarolinaNot yet recruitingEpistaxis | Hereditary Hemorrhagic Telangiectasia