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

Brief Title

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

Official Title

A Phase 2 Evaluation of TRC105 in the Treatment of Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma

Brief Summary

      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.

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.

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Progression-free Survival Rate After 6 Months of Treatment on Study

Secondary Outcome

 CA-125 Response Rate

Condition

Recurrent Ovarian Cancer

Intervention

Carotuximab (TRC105)

Study Arms / Comparison Groups

 Carotuximab (TRC105) alone

Description:  Single arm, open label Carotuximab (TRC105) alone therapy dosed at 10 mg/kg administered intravenously over 1 to 4 hours on days 1, 8, 15 and 22 of each 28 day cycle

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Biological

Estimated Enrollment

Start Date

July 2011

Completion Date

December 2013

Primary Completion Date

August 2012

Eligibility 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

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Charles P Theuer, MD, ,

Location Countries

United States

Location Countries

United States

Administrative Informations

NCT ID

NCT01381861

Organization ID

105OC201

Responsible Party

Sponsor

Study Sponsor

Tracon Pharmaceuticals Inc.

Study Sponsor

Charles P Theuer, MD, Study Director, TRACON Pharmaceuticals

Verification Date

February 2019