Clinical Trial 19003

Cancer Type: Sarcoma
Interventions:Pazopanib; TRC105

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Andrew Brohl

Overview

Study Title

A Randomized Phase 3 Trial of TRC105 and Pazopanib versus Pazopanib Alone In Patients with Advanced Angiosarcoma (TAPPAS)

Summary

The purpose of this research study is to determine the effectiveness and safety of the TRC105 monoclonal antibody when given in combination with pazopanib (also known as Votrient®, an anticancer drug made by Novartis that inhibits blood vessel growth) versus pazopanib alone, and to assess how well participants tolerate the combination. A monoclonal antibody is a substance the body makes as part of an immune response (the body¿s response to infection). TRC105 is an experimental (investigational) cancer drug.

Objective

Primary: - To compare PFS of TRC105 and pazopanib vs. single agent pazopanib in patients with unresectable angiosarcoma. Secondary: - To compare the objective response rate (ORR) of TRC105 and pazopanib vs single agent pazopanib in patients with unresectable angiosarcoma. - To compare overall survival (OS) of TRC105 and pazopanib vs single agent pazopanib in patients with unresectable angiosarcoma. - To compare duration of objective response (DR) of TRC105 and pazopanib vs single agent pazopanib in patients with unresectable angiosarcoma. - To assess the overall safety and tolerability of TRC105 and pazopanib vs single agent pazopanib in patients with unresectable angiosarcoma. - To characterize patient reported outcomes between the two arms of the study. - To characterize the pharmacokinetic (PK) profile of TRC105 and pazopanib between the two arms of the study. - To assess PFS and ORR by Investigator assessment between the two arms of the study. - To characterize the immunogenicity of TRC105.

Inclusion Criteria

  • Histologically-confirmed angiosarcoma that is not amenable to curative intent surgery (e.g., metastatic or bulky disease and disease for which surgical resection would carry an unacceptable risk to the patient).
  • Documented progression on or following most recent systemic chemotherapy regimen (not required for chemotherapy-naïve patients), within 4 months prior to screening.
  • Measurable disease by RECIST v1.1.
  • Age of 18 years or older; in addition, patients age 12 to 17 years may enroll beginning in Cohort 2 if weight ≥ 40 kg.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
  • Resolution of all acute adverse events (AEs) resulting from prior cancer therapies to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03) grade ≤ 1 or to that patient's pre-study baseline (except alopecia or neuropathy).
  • Adequate organ function.
  • Willingness and ability to consent (and assent if under age 18) for self to participate in study.
  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  • Angiosarcoma tumor specimen, if available.
  • Men who are sterile (including vasectomy confirmed by post vasectomy semen analysis) OR agree to use a condom with spermicide and to not donate sperm during the study and for at least 180 days following last dose of TRC105 or pazopanib.
  • Woman of non-child bearing potential due to surgical sterilization, confirmed by medical history or menopause, OR woman of child bearing potential who test negative for pregnancy at time of enrollment based on serum pregnancy test and agree to use at least 2 acceptable methods of birth control, one of which must be highly effective, during the study and for at least 180 days after stopping TRC105 or pazopanib.

  • Exclusion Criteria

  • Prior treatment with TRC105 or any VEGF inhibitor.
  • More than 2 prior lines (may be combination regimens) of chemotherapy for angiosarcoma (neoadjuvant/adjuvant treatment does not count as line of treatment).
  • Current treatment or participation on another therapeutic clinical trial.
  • Women who are pregnant or breastfeeding.
  • Receipt of systemic anticancer therapy, including investigational agents, within 5 times the agent's elimination half-life of starting study treatment.
  • Major surgical procedure or significant traumatic injury within 4 weeks prior to randomization (must have fully recovered from any such procedure or injury); planned surgery (if applicable) or anticipated need for major surgical procedure within next 6 months. NOT considered major procedures and permitted up to 7 days before randomization: Thoracentesis, paracentesis, port placement, laparoscopy, thoracoscopy, tube thoracostomy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, and imaging-guided biopsy for diagnostic purposes.
  • Received wide field radiotherapy ≤ 28 days or limited field radiation for palliation less than 14 days prior to randomization.
  • Uncontrolled hypertension. Anti-hypertensives may be started prior to randomization.
  • Ascites or pleural effusion requiring intervention or that required intervention or recurred within 3 months prior to randomization.
  • Pericardial effusion (except trace effusion identified by echocardiogram) within 3 months prior to randomization.
  • 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 prior to randomization.
  • Angina, myocardial infarction, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism , pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) within 6 months prior to randomization. Deep venous thrombosis within 3 months prior to randomization unrelated to a central venous catheter, unless patient is anti-coagulated without the use of warfarin for at least 2 weeks prior to randomization.
  • Hemoptysis within 6 months prior to randomization.
  • Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to randomization.
  • Known active viral or nonviral hepatitis or cirrhosis.
  • Peptic ulcer in past 3 months prior to randomization, unless treated for condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD).
  • Presence of tumor(s) invading into the heart or great vessels or another location where bleeding is associated with high morbidity including patients with primary cardiac or great vessel angiosarcoma.
  • Gastrointestinal perforation or fistula in the 6 months prior to randomization unless underlying risk has been resolved.
  • Presence of malabsorption syndrome, gastrointestinal disorder, or gastrointestinal surgery that could affect the absorption of pazopanib.
  • Concurrent use or receipt of strong CYP3A4 inducer within 12 days prior to randomization or strong CYP3A4 inhibitor within 7 days prior to randomization.
  • History of severe hypersensitivity reaction to any monoclonal antibody.
  • Additional criteria may apply.