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Trial record 1 of 1 for:    NCT01975519
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A Phase 1B Dose-escalation and Phase 2a Study of TRC105 in Combination With Pazopanib in Patients With Advanced Soft Tissue Sarcoma

This study is currently recruiting participants.
See Contacts and Locations
Verified February 2017 by Tracon Pharmaceuticals Inc.
Sponsor:
Information provided by (Responsible Party):
Tracon Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT01975519
First received: October 23, 2013
Last updated: February 21, 2017
Last verified: February 2017
  Purpose

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 18 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 76 patients will be treated in phase 2, including a cohort of up to 13 patients with angiosarcoma.


Condition Intervention Phase
Advanced Soft Tissue Sarcoma Drug: TRC105 and Pazopanib Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 1B Dose-escalation and Phase 2a Study of TRC105 in Combination With Pazopanib in Patients With Advanced Soft Tissue Sarcoma

Resource links provided by NLM:


Further study details as provided by Tracon Pharmaceuticals Inc.:

Primary Outcome Measures:
  • Determine Maximum Tolerated Dose of TRC105 in Combination with Pazopanib (Phase 1b) [ Time Frame: 5 months ]
    Safety and dose limiting toxicity will be assessed by dose cohort.

  • To estimate the PFS of patients with advanced soft tissue sarcoma by RECIST 1.1 (Phase 2) [ Time Frame: 30 months ]
  • To estimate the ORR in a cohort of patients with angiosarcoma by RECIST 1.1 (Phase 2) [ Time Frame: 18 months ]

Secondary Outcome Measures:
  • Characterize TRC105 pharmacokinetic Concentrations when given with pazopanib [ Time Frame: 14 months ]
    Plasma TRC105 concentrations will be measured at specified timepoints.

  • To explore the correlation of efficacy variables (e.g., PFS and ORR) with endoglin expression on sarcoma [ Time Frame: 30 months ]

Estimated Enrollment: 94
Study Start Date: December 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TRC105 and Pazopanib
Weekly TRC105 in combination with standard dose Pazopanib.
Drug: TRC105 and Pazopanib
Weekly TRC105 in combination with standard dose Pazopanib.
Other Names:
  • Chimeric Antibody (TRC105) to CD105
  • Votrient

Detailed Description:
Pazopanib is an oral inhibitor of multiple receptor tyrosine kinases, including vascular endothelial growth factor receptor VEGFR-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations. These receptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression. Pazopanib is approved for the treatment of advanced soft tissue sarcoma, following progression on one prior systemic therapy, based on improved progression free survival. TRC105 is an antibody to CD105, an important angiogenic target on vascular endothelial cells that is distinct from VEGFR. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models and complements the activity of bevacizumab and multi-kinase inhibitors that target the VEGFR. In a phase 1 study of advanced solid tumors, TRC105 therapy caused a global reduction in angiogenic biomarkers and reduced tumor burden at doses that were well-tolerated. In a phase 1b study, the combination of TRC105 and bevacizumab produced radiographic reductions in tumor volume in bevacizumab-refractory patients, and was well tolerated. TRC105 potentiates bevacizumab and VEGFR tyrosine kinases (VEGFR TKI) in preclinical models. By targeting a non-VEGF pathway that is upregulated following VEGF inhibition, TRC105 has the potential to complement VEGFR TKIs and could represent a major advance in cancer therapy. Together, the use of TRC105 with pazopanib may result in more effective angiogenesis inhibition and improved clinical efficacy over that seen with pazopanib alone.
  Eligibility

Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically confirmed unresectable soft tissue sarcoma (i.e., non-GIST, non-adipocytic) that has progressed following treatment with chemotherapy. Prior pazopanib is allowed if the drug was not discontinued for toxicity ( Phase 1 only)
  2. Histologically confirmed metastatic soft tissue sarcoma (i.e., non-GIST, non-adipocytic) 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)
  3. Histologically confirmed locally advanced (e.g. unresectable) or metastatic angiosarcoma that has progressed by RECIST following treatment with prior systemic treatment. . Prior pazopanib is allowed if the drug was not discontinued for toxicity (Phase 2 angiosarcoma cohort).
  4. Measurable disease by RECIST
  5. Age of 12 years or older (patient must weigh ≥ 40 kg)
  6. ECOG performance status ≤ 1
  7. Resolution of all acute adverse events resulting from prior cancer therapies to NCI CTCAE grade ≤ 1 or baseline (except alopecia or neuropathy)
  8. Adequate organ function
  9. Willingness and ability to consent for self and to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
  10. Available archival tumor specimen of the soft tissue sarcoma that meets inclusion criterion #1, #2 or #3.

Exclusion Criteria:

  1. Prior treatment with TRC105
  2. Prior treatment with a VEGFR TKI (including pazopanib) (Phase 2 only)
  3. Current treatment on another therapeutic clinical trial
  4. Receipt of a small molecule anticancer agent, including an investigational anticancer small molecule, within 14 days of starting study treatment
  5. Receipt of systemic anticancer therapy, including investigational agents, within 28 days of starting study treatment. If anticancer therapy was given within 28 days of starting study treatment, patients may be included if 5 times the elimination half-life of the drug has passed. a biologic anticancer agent (e.g., antibody), including an investigational anticancer antibody, within 28 days of starting study treatment
  6. 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). Note: the following are not considered to be major procedures and are permitted up to 7 days before therapy initiation: Thoracentesis, paracentesis, port placement, laparoscopy, thorascopy, tube thoracostomy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, incisional biopsies, imaging-guided biopsy for diagnostic purposes, and routine dental procedures
  7. Patients who have received wide field radiotherapy ≤ 28 days (defined as > 50% of volume of pelvic bones or equivalent) 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
  8. Uncontrolled chronic hypertension defined as systolic > 150 or diastolic > 90 despite optimal therapy (initiation or adjustment of BP medication prior to study entry is allowed provided that the average of 3 BP readings at a visit prior to enrollment is < 150/90 mm Hg)
  9. Significant ascites or pericardial or pleural effusion
  10. History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease. Patients with radiated or resected lesions are permitted, provided the lesions are fully treated and inactive, patients are asymptomatic, and no steroids have been administered for at least 28 days.
  11. 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.
  12. Active bleeding or pathologic condition that carries a high risk of bleeding (e.g. hereditary hemorrhagic telangiectasia). Patients who have been uneventfully anti-coagulated with low molecular weight heparin are eligible.
  13. Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy
  14. Known active viral or nonviral hepatitis or cirrhosis
  15. History of hemorrhage or hemoptysis (> ½ teaspoon bright red blood) within 3 months of starting study treatment
  16. History of peptic ulcer within the past 3 months of treatment, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD) within 28 days of starting study treatment
  17. History of gastrointestinal perforation or fistula in the past 6 months, or while previously on antiangiogenic therapy, unless underlying risk has been resolved (e.g., through surgical resection or repair)
  18. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
  19. 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 (Table 8)
  20. Pregnancy or breastfeeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01975519

Contacts
Contact: Clinical Trials information Clinicaltrials@traconpharma.com

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35243
United States, California
Sarcoma Oncology Center Active, not recruiting
Santa Monica, California, United States, 90403
United States, Florida
Mayo Clinic Jacksonville Recruiting
Jacksonville, Florida, United States, 32224
United States, Minnesota
Mayo Clinic Rochester Recruiting
Rochester, Minnesota, United States, 55905
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 92122
Mount Sinai School of Medicine-Tisch Cancer Institute Active, not recruiting
New York, New York, United States, 10029
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27710
United States, Texas
Mary Crowley Cancer Research Center Recruiting
Dallas, Texas, United States, 75230
United States, Utah
University of Utah Active, not recruiting
Salt Lake City, Utah, United States
Sponsors and Collaborators
Tracon Pharmaceuticals Inc.
  More Information

Responsible Party: Tracon Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT01975519     History of Changes
Other Study ID Numbers: 105SAR101
Study First Received: October 23, 2013
Last Updated: February 21, 2017

Keywords provided by Tracon Pharmaceuticals Inc.:
TRC105
CD105
Endoglin
Angiogenesis Inhibitor
STS
Soft Tissue Sarcoma
TKI
Tyrosine Kinase Inhibitor
Pazopanib
Votrient
Advanced Soft Tissue Sarcoma
Angiosarcoma

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 27, 2017