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Advanced AngiosarcomaPhase 3TAPPASNCT02979899

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

A Phase 3 study testing TRC105 and Votrient in people with Advanced Angiosarcoma, run by Tracon Pharmaceuticals Inc. at 39 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Advanced Angiosarcoma
What is being tested?
TRC105 and Votrient
Could I receive a placebo?
No, everyone receives an active treatment
How many people
128 participants
Where
39 sitesin 8 countries
Study dates
13 Feb 2017to 31 Aug 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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
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  • 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
  • Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to randomization
  • Known active viral or nonviral hepatitis or cirrhosis
  • Peptic ulcer within the past 3 months prior to randomization, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD)
  • 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
  • Gastrointestinal perforation or fistula in the 6 months prior to randomization unless underlying risk has been resolved (e.g., through surgical resection or repair)
  • Presence of a malabsorption syndrome, gastrointestinal disorder, or gastrointestinal surgery that could affect the absorption of pazopanib
  • 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
  • Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
  • Active infection that requires systemic treatment
  • 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)
  • History of severe hypersensitivity reaction to any monoclonal antibody
  • 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

Trial locations and contacts

39 sites in 8 countries.

39 sites in 8 countries

United States26 sites

  • University of Colorado Denver

    Aurora, Colorado, 80045

  • Johns Hopkins

    Baltimore, Maryland, 21231

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Ohio State University

    Columbus, Ohio, 43202

  • Duke University

    Durham, North Carolina, 27705

  • MD Anderson

    Houston, Texas, 77230

  • University of Iowa

    Iowa City, Iowa, 52242

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32224

  • Northwell Health

    Lake Success, New York, 11042

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Vanderbilt University

    Nashville, Tennessee, 37212

  • MSKCC

    New York, New York, 10017

  • Stanford University

    Palo Alto, California, 94304

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • UPMC

    Pittsburgh, Pennsylvania, 15232

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55905

  • University of Utah, Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • Northside Hospital

    Sandy Springs, Georgia, 30342

  • Sarcoma Oncology Center

    Santa Monica, California, 90403

  • University of Washinton

    Seattle, Washington, 98109

  • Washington University St. Louis

    St Louis, Missouri, 63110

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • University of Arizona Cancer Center

    Tucson, Arizona, 85724

Other trials in United States

France4 sites

  • Institut Bergonié

    Bordeaux

  • Centre Oscar Lambret

    Lille

  • Centre Léon Bérard

    Lyon

  • Institut Gustave Roussy

    Villejuif

Other trials in France

Germany3 sites

  • Helios Klinikum

    Bad Saarow

  • Mannheim University Medical Center

    Mannheim

  • Klinikum derUniversitat Munchen

    Munich

Other trials in Germany

Spain2 sites

  • Institut Català d'Oncologia (ICO)

    Barcelona

  • 12 de Octubre University Hospital

    Madrid

Other trials in Spain

Austria1 site

  • Medical University,Vienna

    Vienna

Other trials in Austria

Italy1 site

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan

Other trials in Italy

Poland1 site

  • Memorial Cancer Center and Institute of Oncology

    Warsaw

Other trials in Poland

United Kingdom1 site

  • Royal Marsden NHS

    Chelsea

Other trials in United Kingdom

About this study

Official title: A Randomized Phase 3 Trial of TRC105 and Pazopanib Versus Pazopanib Alone in Patients With Advanced Angiosarcoma (TAPPAS)

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.

Read the 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.

Being tested
TRC105, Votrient
Keywords
angiosarcoma
Medical subject headings
Hemangiosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TRC105Biological

    Also called anti-endoglin antibody, carotuximab

    TRC105 antibody

  • VotrientDrug

    Also called pazopanib

    pazopanib

Study groups in NCT02979899
Study groupRoleWhat they receive
TRC105 plus votrientExperimentalweekly TRC105 i.v. in combination with standard dose votrient by mouth, once daily
Receives: Biological: TRC105; Drug: Votrient
votrientActive comparatorstandard dose votrient by mouth, once daily
Receives: Drug: Votrient

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. Objective Response Rate of Patients With Unresectable Angiosarcoma

    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.

    Measured: 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)

  2. Overall Survival of Patients With Unresectable Angiosarcoma

    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)

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

  3. To Characterize Patient Reported Outcomes Between the Two Arms of the Study

    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.

    Measured: Screening and 9 weeks (Cycle 3 Day 1)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Dec 2016 (estimated)
  2. Study start13 Feb 2017
  3. Primary completion11 Apr 2019
  4. Study completion31 Aug 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
128 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02979899
Sponsor's protocol ID
105SAR301
Acronym
TAPPAS
Status last verified
May 2020
First submitted
29 Nov 2016
Last updated
12 May 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 35357396

  • 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.

    PubMed 30357394

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing TRC105 and Votrient in people with Advanced Angiosarcoma, run by Tracon Pharmaceuticals Inc. at 39 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 39 sites in United States, France, Germany, Spain, Austria and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02979899, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2020.

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