Working… Menu
Trial record 1 of 2 for:    tracon | Angiosarcoma
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02979899
Recruitment Status : Completed
First Posted : December 2, 2016
Results First Posted : May 12, 2020
Last Update Posted : May 12, 2020
Information provided by (Responsible Party):
Tracon Pharmaceuticals Inc.

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.

Condition or disease Intervention/treatment Phase
Advanced Angiosarcoma Biological: TRC105 Drug: Votrient Phase 3

Detailed Description:

TRC105 (carotuximab) is a monoclonal antibody to endoglin (CD105), an essential angiogenic target highly expressed on tumor vessels that is distinct from VEGFR. Endoglin is also expressed directly on tumor cells in angiosarcoma and is upregulated following VEGF inhibition. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models and complements the activity of bevacizumab and multi-kinase inhibitors that target the VEGFR.

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.

By targeting a non-VEGF pathway that is upregulated following VEGF inhibition, TRC105 has the potential to complement VEGFR tyrosine kinase inhibitors (TKIs) and could represent a major advance in the treatment of angiosarcoma. Together, the use of TRC105 with pazopanib may result in more effective angiogenesis inhibition and improved clinical efficacy over that seen with pazopanib alone.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 128 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase 3 Trial of TRC105 and Pazopanib Versus Pazopanib Alone in Patients With Advanced Angiosarcoma (TAPPAS)
Actual Study Start Date : February 13, 2017
Actual Primary Completion Date : April 11, 2019
Actual Study Completion Date : August 31, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Pazopanib

Arm Intervention/treatment
Experimental: TRC105 plus votrient
weekly TRC105 i.v. in combination with standard dose votrient by mouth, once daily
Biological: TRC105
TRC105 antibody
Other Names:
  • anti-endoglin antibody
  • carotuximab

Drug: Votrient
Other Name: pazopanib

Active Comparator: votrient
standard dose votrient by mouth, once daily
Drug: Votrient
Other Name: pazopanib

Primary Outcome Measures :
  1. Progression Free Survival of Patients With Unresectable Angiosarcoma [ Time Frame: 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) ]
    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.

Secondary Outcome Measures :
  1. Objective Response Rate of Patients With Unresectable Angiosarcoma [ Time Frame: 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) ]
    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions: Complete Response (CR) is disappearance of all target lesions; Partial Response (PR) is >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Overall response rate is defined as the number of patients with a best response designation of complete response or partial response recorded between the date of randomization and the date of documented progression.

  2. Overall Survival of Patients With Unresectable Angiosarcoma [ Time Frame: from beginning of study to cut off date of interim analysis (25 months) ]
    Overall survival is the number of death events at 25 months, including all on-study and off-study deaths (past post-treatment 28-day follow up visit)

  3. To Characterize Patient Reported Outcomes Between the Two Arms of the Study [ Time Frame: Screening and 9 weeks (Cycle 3 Day 1) ]
    Patient reported outcomes as measured by the EuroQol five dimensions questionnaire (EQ-5D-5L) and the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30). The EORTC QLQ-C30 health scale is on a scale of 1 to 7, with 1 being poor health and 7 being excellent health. The EQ-5D-5L scale is on a scale of 0 to 100, with 0 being the worst health one can imagine, and 100 being the best health one can imagine.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. 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.
  2. Documented progression on or following most recent systemic chemotherapy regimen (not required for chemotherapy-naïve patients), within 4 months prior to screening
  3. Measurable disease by RECIST v1.1
  4. Age of 18 years or older; in addition, patients age 12 to 17 years may enroll beginning in Cohort 2 if weight ≥ 40 kg
  5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  6. 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)
  7. Adequate organ function
  8. Willingness and ability to consent (and assent if under age 18) for self to participate in study
  9. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
  10. Angiosarcoma tumor specimen, if available
  11. Men who are sterile (including vasectomy confirmed by post vasectomy semen analysis) OR agree to use a condom with spermicide (refer to Section and to not donate sperm during the study and for at least 180 days following last dose of TRC105 or pazopanib
  12. 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

Exclusion Criteria:

  1. Prior treatment with TRC105
  2. Prior treatment with any VEGF inhibitor
  3. More than two prior lines (may be combination regimens) of chemotherapy for angiosarcoma (neoadjuvant/adjuvant treatment does not count as a line of treatment)
  4. Current treatment or participation on another therapeutic clinical trial
  5. Women who are pregnant or breastfeeding
  6. Receipt of systemic anticancer therapy, including investigational agents, within 5 times the agent's elimination half-life of starting study treatment
  7. 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
  8. 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
  9. 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.
  10. Ascites or pleural effusion requiring intervention or that required intervention or recurred within three months prior to randomization
  11. Pericardial effusion (except trace effusion identified by echocardiogram) within three months prior to randomization
  12. 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
  13. 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
  14. 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
  15. Hemoptysis (> ½ teaspoon [2.5 mL] of bright red blood) within 6 months prior to randomization
  16. Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to randomization
  17. Known active viral or nonviral hepatitis or cirrhosis
  18. Peptic ulcer within the past 3 months prior to randomization, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD)
  19. Presence of tumor(s) invading into the heart or great vessels (including carotid artery) or another location where bleeding is associated with high morbidity including patients with primary cardiac or great vessel angiosarcoma
  20. Gastrointestinal perforation or fistula in the 6 months prior to randomization unless underlying risk has been resolved (e.g., through surgical resection or repair)
  21. Presence of a malabsorption syndrome, gastrointestinal disorder, or gastrointestinal surgery that could affect the absorption of pazopanib
  22. History of prior malignancy except adequately treated basal cell or squamous cell skin cancer or adequately treated, with curative intent, cancer from which the patient is currently in complete remission per Investigator's judgment; patients with history of breast cancer and no evidence of disease on hormonal therapy to prevent recurrence and patients with prostate cancer on adjuvant hormonal therapy with undetectable PSA are eligible
  23. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
  24. Active infection that requires systemic treatment
  25. Concurrent use or receipt of a strong CYP3A4 inducer within 12 days prior to randomization or a strong CYP3A4 inhibitor within 7 days prior to randomization (see Table 10)
  26. History of severe hypersensitivity reaction to any monoclonal antibody
  27. Other severe acute or chronic medical (including bone marrow suppressive diseases) or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation, impede the ability of the patient to complete all protocol-specified activities, or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02979899

Hide Hide 39 study locations
Layout table for location information
United States, Arizona
University of Arizona Cancer Center
Tucson, Arizona, United States, 85724
United States, California
Stanford University
Palo Alto, California, United States, 94304
Sarcoma Oncology Center
Santa Monica, California, United States, 90403
United States, Colorado
University of Colorado Denver
Aurora, Colorado, United States, 80045
United States, Florida
Mayo Clinic Jacksonville
Jacksonville, Florida, United States, 32224
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Northside Hospital
Sandy Springs, Georgia, United States, 30342
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Maryland
Johns Hopkins
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Minnesota
Mayo Clinic Rochester
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University St. Louis
Saint Louis, Missouri, United States, 63110
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Northwell Health
Lake Success, New York, United States, 11042
New York, New York, United States, 10017
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27705
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Ohio State University
Columbus, Ohio, United States, 43202
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37212
United States, Texas
MD Anderson
Houston, Texas, United States, 77230
United States, Utah
University of Utah, Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
United States, Washington
University of Washinton
Seattle, Washington, United States, 98109
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Medical University,Vienna
Wien, Austria
Institut Bergonié
Bordeaux, France
Centre Oscar Lambret
Lille, France
Centre Léon Bérard
Lyon, France
Institut Gustave Roussy
Villejuif, France
Helios Klinikum
Bad Saarow, Germany
Mannheim University Medical Center
Mannheim, Germany
Klinikum derUniversitat Munchen
Munich, Germany
Fondazione IRCCS Istituto Nazionale dei Tumori
Milano, Italy
Memorial Cancer Center and Institute of Oncology
Warszawa, Poland
Institut Català d'Oncologia (ICO)
Barcelona, Spain
12 de Octubre University Hospital
Madrid, Spain
United Kingdom
Royal Marsden NHS
Chelsea, United Kingdom
Sponsors and Collaborators
Tracon Pharmaceuticals Inc.
Layout table for investigator information
Study Director: Charles Theuer, MD TRACON Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Tracon Pharmaceuticals Inc.:
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Tracon Pharmaceuticals Inc. Identifier: NCT02979899    
Other Study ID Numbers: 105SAR301
First Posted: December 2, 2016    Key Record Dates
Results First Posted: May 12, 2020
Last Update Posted: May 12, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tracon Pharmaceuticals Inc.:
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Vascular Tissue