Trial of TRC105 and Pazopanib Versus Pazopanib Alone in Patients With Advanced Angiosarcoma

NCT02979899 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 105SAR301
• Study Type: interventional
• Target: 128
• Locations: 8 countries
• Sites: 39

Brief Summary

This is a study of TRC105 in combination with standard dose pazopanib compared to single agent pazopanib in patients with angiosarcoma 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) who have not received pazopanib or TRC105 previously.

Conditions

Advanced Angiosarcoma

Keywords

angiosarcoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival of Patients With Unresectable Angiosarcoma

  Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Progression free survival is defined as time from randomization to either first disease progression (per independent radiology review of images by RECIST 1.1) or death from any cause.

  from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to cut off date of interim analysis (25 months)

Secondary Outcomes (3)

• Objective Response Rate of Patients With Unresectable Angiosarcoma

  from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to cut off date of interim analysis (25 months)

• Overall Survival of Patients With Unresectable Angiosarcoma

  from beginning of study to cut off date of interim analysis (25 months)

• To Characterize Patient Reported Outcomes Between the Two Arms of the Study

  Screening and 9 weeks (Cycle 3 Day 1)

Study Arms (2)

TRC105 plus votrient

EXPERIMENTAL

weekly TRC105 i.v. in combination with standard dose votrient by mouth, once daily

Biological: TRC105; Drug: Votrient

votrient

ACTIVE COMPARATOR

standard dose votrient by mouth, once daily

Drug: Votrient

Interventions

TRC105 BIOLOGICAL

TRC105 antibody

Also known as: anti-endoglin antibody, carotuximab

TRC105 plus votrient

Votrient DRUG

pazopanib

Also known as: pazopanib

TRC105 plus votrient; votrient

Eligibility Criteria

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

You may qualify if:

• 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). Pathology report will be reviewed by sponsor prior to randomization.
• 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 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 (refer to Section 2.6.1.3) 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 (at least 6 weeks following surgical bilateral oophorectomy with or without hysterectomy or tubal ligation) confirmed by medical history or menopause (i.e., no menstrual bleeding for more than 12 months in a women aged 45 years or more), 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

You may not qualify if:

• Prior treatment with TRC105
• Prior treatment with any VEGF inhibitor
• More than two prior lines (may be combination regimens) of chemotherapy for angiosarcoma (neoadjuvant/adjuvant treatment does not count as a 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 and must have fully recovered from any such procedure or injury; planned surgery (if applicable) or the anticipated need for a major surgical procedure within the next six months. Note: the following are not considered to be major procedures and are 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
• 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 randomization
• Uncontrolled hypertension defined as systolic \> 150 or diastolic \> 100 mm Hg on the average of the 3 most recent BP readings. Anti-hypertensives may be started prior to randomization.
• Ascites or pleural effusion requiring intervention or that required intervention or recurred within three months prior to randomization
• Pericardial effusion (except trace effusion identified by echocardiogram) within three 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 the patient is anti-coagulated without the use of warfarin for at least 2 weeks prior to randomization. In this situation, low molecular weight heparin is preferred
• Active bleeding or pathologic condition that carries a high risk of bleeding (e.g., hereditary hemorrhagic telangiectasia). Patients with bleeding cutaneous lesions not actively requiring transfusions are eligible. Patients who have been uneventfully anti-coagulated with low molecular weight heparin are eligible
• Hemoptysis (\> ½ teaspoon \[2.5 mL\] of bright red blood) within 6 months prior to randomization

Sponsors & Collaborators

• Tracon Pharmaceuticals Inc.: lead

Study Sites (39)

University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northside Hospital

Sandy Springs, Georgia, 30342, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University St. Louis

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Northwell Health

Lake Success, New York, 11042, United States

Location

MSKCC

New York, New York, 10017, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43202, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

UPMC

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt University

Nashville, Tennessee, 37212, United States

Location

MD Anderson

Houston, Texas, 77230, United States

Location

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

University of Washinton

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Medical University,Vienna

Vienna, Austria

Location

Institut Bergonié

Bordeaux, France

Location

Centre Oscar Lambret

Lille, France

Location

Centre Léon Bérard

Lyon, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Helios Klinikum

Bad Saarow, Germany

Location

Mannheim University Medical Center

Mannheim, Germany

Location

Klinikum derUniversitat Munchen

Munich, Germany

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Location

Memorial Cancer Center and Institute of Oncology

Warsaw, Poland

Location

Institut Català d'Oncologia (ICO)

Barcelona, Spain

Location

12 de Octubre University Hospital

Madrid, Spain

Location

Royal Marsden NHS

Chelsea, United Kingdom

Location

Related Publications (2)

• Jones RL, Ravi V, Brohl AS, Chawla S, Ganjoo KN, Italiano A, Attia S, Burgess MA, Thornton K, Cranmer LD, Cheang MCU, Liu L, Robertson L, Adams B, Theuer C, Maki RG. Efficacy and Safety of TRC105 Plus Pazopanib vs Pazopanib Alone for Treatment of Patients With Advanced Angiosarcoma: A Randomized Clinical Trial. JAMA Oncol. 2022 May 1;8(5):740-747. doi: 10.1001/jamaoncol.2021.3547.

  PMID: 35357396 DERIVED

• Mehta CR, Liu L, Theuer C. An adaptive population enrichment phase III trial of TRC105 and pazopanib versus pazopanib alone in patients with advanced angiosarcoma (TAPPAS trial). Ann Oncol. 2019 Jan 1;30(1):103-108. doi: 10.1093/annonc/mdy464.

  PMID: 30357394 DERIVED

MeSH Terms

Conditions

Hemangiosarcoma

Interventions

carotuximab; pazopanib

Condition Hierarchy (Ancestors)

Sarcoma; 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

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2016
• First Posted: December 2, 2016
• Study Start: February 13, 2017
• Primary Completion: April 11, 2019
• Study Completion: August 31, 2019
• Last Updated: May 12, 2020
• Results First Posted: May 12, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4); DE (3); AU (1); GB (1); US (26); ES (2); PL (1); IT (1)