Evaluation of TRC105 in the Treatment of Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tracon Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT01381861
First received: June 21, 2011
Last updated: December 3, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to evaluate the safety and efficacy of TRC105 in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.


Condition Intervention Phase
Recurrent Ovarian Cancer
Fallopian Tube Carcinoma
Primary Peritoneal Carcinoma
Biological: Chimeric monoclonal antibody (TRC105) to CD105
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Evaluation of TRC105 in the Treatment of Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma

Resource links provided by NLM:


Further study details as provided by Tracon Pharmaceuticals Inc.:

Primary Outcome Measures:
  • Estimate the proportion of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who survive progression-free for at least 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Estimate the proportion of patients who have objective tumor response (complete or partial) by RECIST 1.1 criteria [ Time Frame: Every 2 cycles ] [ Designated as safety issue: No ]
  • Determine the frequency of adverse events as assessed by NCI CTCAE (Version 4.0) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Estimate the CA-125 response rate by GCIG criteria [ Time Frame: Every 2 cycles ] [ Designated as safety issue: No ]
  • To estimate median duration of progression-free survival [ Time Frame: 6 - 12 months ] [ Designated as safety issue: No ]
  • Measure peak and trough serum concentrations of TRC105 with ELISA and correlate with response, PFS, survival, adverse events and baseline characteristics [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Evaluate TRC105 Immunogenicity [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Determine the severity of adverse events as assessed by NCI CTCAE [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • To estimate median duration of overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 23
Study Start Date: July 2011
Study Completion Date: December 2013
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TRC105 Biological: Chimeric monoclonal antibody (TRC105) to CD105
10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle
Other Names:
  • TRC105
  • NSC#754227

Detailed Description:

Angiogenesis plays a central role in the progression of epithelial ovarian cancer. In mouse models, VEGF-inhibitors diminish ovarian tumor growth, metastasis and malignant ascites formation. Independent Phase 2 trials have demonstrated single-agent activity for bevacizumab in recurrent ovarian cancer, and randomized controlled Phase 3 trials are ongoing in the first-line setting (GOG 0218 and ICON-7) and for recurrent disease (GOG 0213, OCEANS).

TRC105 is an antibody to CD105, an important non-VEGF angiogenic target on vascular endothelial cells. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models. 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. We hypothesize that TRC105 will have single-agent activity in recurrent ovarian cancer. By targeting a non-VEGF pathway, TRC105 has the potential to complement VEGF inhibitors which could represent a major advance in ovarian cancer therapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma
  • Measurable disease per RECIST 1.1
  • At least one "target lesion" per RECIST 1.1
  • Patients must have GOG Performance Status of 0 or 1
  • Patients must have a life expectancy of ≥ 3 months
  • Resolution of all acute toxic effects of prior therapy
  • Free of active infection requiring antibiotics
  • Must have had one prior platinum-based chemotherapeutic regimen for management of primary disease
  • Patients could have received one additional cytotoxic regimen for management of recurrent disease
  • Prior therapy directed at the malignant tumor, including hormonal and immunologic agents, must be discontinued at least three weeks prior to registration. Continuation of hormone replacement therapy is permitted.
  • Adequate bone marrow function, renal function, hepatic function, neurologic function, blood coagulation parameters
  • Negative serum pregnancy test and effective form of contraception for patients of childbearing potential

Exclusion Criteria:

  • Previous treatment with TRC105
  • Current treatment on another therapeutic clinical trial
  • Receipt of an investigational agent within 28 days of starting study treatment
  • Serious, non-healing wounds, ulcers, or bone fractures.
  • Active bleeding or pathologic conditions that carry a high risk of bleeding
  • Patients with tumor involving major vessels or transmural bowel wall involvement by tumor
  • Use of thrombolytic or anticoagulant agents (except heparin to maintain i.v. catheters) within 10 days prior to the first dose of TRC105
  • History of deep venous thrombosis (DVT)(except patients who have received adequate anticoagulation are eligible, and may continue on anticoagulation if appropriate)
  • History of peptic ulcer disease or erosive gastritis within the past 6 months
  • Known active viral or nonviral hepatitis
  • History or evidence of CNS disease
  • Clinically significant cardiovascular disease
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human, chimeric, or humanized antibodies
  • Pregnant or nursing
  • Under the age of 18
  • Patients with or with anticipation of invasive procedures including major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to treatment with TRC105
  • History of other invasive malignancies, except non-melanoma skin cancer and other cancers that have been treated with no evidence of disease within the last 3 years
  • History of primary endometrial cancer diagnosed within the last 5 years, unless all of the following conditions are met: Stage not greater than I-B; no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell or other FIGO Grade 3 lesions
  • Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last five years are excluded. Patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed > 3 years prior to registration, and patient remains free of recurrent or metastatic disease
  • Prior radiotherapy to any portion of the abdominal cavity or pelvis
  • Patients with clinical symptoms or signs of gastrointestinal obstruction and who require parenteral hydration and/or nutrition
  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: NCT01381861

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35249
United States, California
University of California, San Diego
La Jolla, California, United States, 92093
University of Southern California
Los Angeles, California, United States, 90033
United States, Florida
Palm Beach Cancer Institute
West Palm Beach, Florida, United States, 33401
United States, Indiana
Indiana University-Bren and Melvin Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77230
Sponsors and Collaborators
Tracon Pharmaceuticals Inc.
Investigators
Study Director: Charles P Theuer, MD TRACON Pharmaceuticals
  More Information

No publications provided

Responsible Party: Tracon Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT01381861     History of Changes
Other Study ID Numbers: 105OC201
Study First Received: June 21, 2011
Last Updated: December 3, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Ovarian Neoplasms
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014