Clinical trial NCT01381861: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Ovarian Cancer
Fallopian Tube Carcinoma
Primary Peritoneal Carcinoma
Lead sponsor: Tracon Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2011-06-27
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression-free Survival Rate After 6 Months of Treatment on Study
timeFrame: 6 months
measure: Proportion of Patients Who Have Objective Tumor Response
timeFrame: Every 2 cycles
measure: Adverse Events
timeFrame: 28 days
Secondary outcomes:
measure: CA-125 Response Rate
timeFrame: Every 2 cycles
measure: Serum Concentrations of TRC105
timeFrame: Cycle 1 Day 15
measure: TRC105 Immunogenicity
timeFrame: 1 year
measure: Severity of Adverse Events
timeFrame: 28 days post last dose of TRC105
measure: Overall Survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: West Palm Beach
country: United States
facility: Palm Beach Cancer Institute
state: Florida
city: Indianapolis
country: United States
facility: Indiana University-Bren and Melvin Simon Cancer Center
state: Indiana
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: TRACON Pharmaceuticals
name: Charles P Theuer, MD
role: STUDY_DIRECTOR
References: