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

Primary Peritoneal Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01381861
• Other study ID #: 105OC201
• Status: Completed
• Phase: Phase 2
• Start date: July 2011
• Est. completion date: December 2013

Study information

• Verified date: February 2019
• Source: Tracon Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: December 2013
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Fallopian Tube Carcinoma
• Fallopian Tube Neoplasms
• Primary Peritoneal Carcinoma
• Recurrent Ovarian Cancer

Intervention

Biological:
• Carotuximab (TRC105)
Carotuximab (TRC105) 10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	MD Anderson Cancer Center	Houston	Texas
United States	Indiana University-Bren and Melvin Simon Cancer Center	Indianapolis	Indiana
United States	University of California, San Diego	La Jolla	California
United States	University of Southern California	Los Angeles	California
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Palm Beach Cancer Institute	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Tracon Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival Rate After 6 Months of Treatment on Study	Number of patients ongoing within the study who have not progressed after 6 months of treatment	6 months
Primary	Proportion of Patients Who Have Objective Tumor Response	Proportion of patients who have objective tumor response (complete or partial) by RECIST 1.1	Every 2 cycles
Primary	Adverse Events	Frequency of adverse events as assessed by NCI CTCAE (Version 4.0)	28 days
Secondary	CA-125 Response Rate	CA-125 response rate by GCIG criteria	Every 2 cycles
Secondary	Serum Concentrations of TRC105	Median peak and trough concentration of TRC105 by ELISA in ug/mL	Cycle 1 Day 15
Secondary	TRC105 Immunogenicity	TRC105 Anti-Drug Antibody (ADA) Immunogenicity by ELISA	1 year
Secondary	Severity of Adverse Events	Severity of adverse events by NCI CTCAE	28 days post last dose of TRC105
Secondary	Overall Survival	Median overall survival	2 years