A Phase 2 Evaluation of TRC105 in the Treatment of Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 23
- 试验地点
- 13
- 主要终点
- Proportion of Patients Who Have Objective Tumor Response
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Carotuximab (TRC105) alone
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
干预措施: Carotuximab (TRC105) (Biological)
结局指标
主要结局
Proportion of Patients Who Have Objective Tumor Response
时间窗: Every 2 cycles
Proportion of patients who have objective tumor response (complete or partial) by RECIST 1.1
Adverse Events
时间窗: 28 days
Frequency of adverse events as assessed by NCI CTCAE (Version 4.0)
Progression-free Survival Rate After 6 Months of Treatment on Study
时间窗: 6 months
Number of patients ongoing within the study who have not progressed after 6 months of treatment
次要结局
- TRC105 Immunogenicity(1 year)
- Severity of Adverse Events(28 days post last dose of TRC105)
- Overall Survival(2 years)
- CA-125 Response Rate(Every 2 cycles)
- Serum Concentrations of TRC105(Cycle 1 Day 15)