A Phase II Study of CCI-779 in Combination With Bevacizumab in Stage III or IV Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 2
- 主要终点
- Objective Tumor Response (Complete Response and Partial Response) and Progression in Participants With Stage III or IV Melanoma Following Treatment With Temsirolimus and Bevacizumab
研究概览
简要总结
This phase II trial is studying how well giving temsirolimus together with bevacizumab works in treating patients with stage III or stage IV malignant melanoma. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of malignant melanoma by blocking blood flow to the tumor. Giving temsirolimus together with bevacizumab may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. Determine the objective tumor response rate (complete response and partial response) in patients with stage III or IV melanoma treated with temsirolimus and bevacizumab.
SECONDARY OBJECTIVES:
I. Describe the adverse event profile of this regimen in these patients. II. Determine the efficacy of this regimen, in terms of progression-free survival, in these patients.
III. Compare pre- vs post-treatment measurements of biomarkers and vascular system/immune system parameters in patients treated with this regimen.
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
- •Histologically or cytologically confirmed melanoma
- •Stage III or IV disease
- •Recurrent disease allowed
- •Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension as ≥ 20 mm with conventional techniques OR ≥ 10 mm with spiral CT scan
- •Tumor lesions in previously irradiated areas are not considered measurable disease
- •Prior brain metastases allowed provided all of the following criteria are met:
- •No more than a total of 5 brain metastases
- •All metastases are no more than 2.5 cm
- •Surgically resected or have been treated with gamma-knife or stereotactic radiosurgery
- •More than 30 days since prior disease progression
- •More than 30 days since prior steroids for managing brain metastases
- •Concurrent steroids for other reasons allowed provided the dose is < that required for managing brain metastases
- •Disease accessible for core needle biopsy, incisional biopsy, and/or surgical resection and meets one of the following criteria:
- •One large tumor deposit ≥ 5 cm³ from which biopsies can be harvested multiple times
- •Multiple deposits that can be biopsied or excised individually on different dates, measured as follows:
- •One lesion ≥ 5 cm^3
- •Two lesions ≥ 3 cm^3
- •Three lesions ≥ 2 cm^3
- •ECOG performance status 0-1
- •Weight ≥ 110 pounds (without clothes)
- •WBC ≥ 3,000 mm³
- •Absolute neutrophil count ≥ 1,500/mm³
- •Platelet count ≥ 100,000/mm³
- •Bilirubin normal
- •AST and ALT ≤ 2.5 times upper limit of normal
- •Creatinine normal OR creatinine clearance ≥ 60 mL/min
- •Urine protein: creatinine ratio < 1.0 OR 24-hour urine protein < 1,000 mg
- •Fasting cholesterol < 350 mg/dL (cholesterol medications are allowed)
- •Fasting triglycerides < 400 mg/dL
- •PT INR ≤ 1.5 (unless on full-dose anticoagulants)
- •Hematocrit < 41% (for males) or < 38% (for females)
- •None of the following within the past 4 weeks:
- •Uncontrolled intercurrent illness
- •Ongoing or active acute (CTCAE v.3 grade 3 or 4) infection
- •Abdominal fistula
- •Gastrointestinal perforation
- •Intra-abdominal abscess
- •Serious or nonhealing wound, ulcer, or bone fracture
- •No psychiatric illness or social situations that would preclude study compliance
- •No clinically significant cardiovascular disease, including the following:
- •Cerebrovascular accident within the past 6 months
- •Transient ischemic attack within the past 6 months
- •Myocardial ischemia within the past 6 months
- •Myocardial infarction within the past 6 months
- •Other thromboembolic event within the past 6 months
- •Unstable angina within the past 6 months
- •Uncontrolled hypertension (i.e., hypertension despite maximal therapy)
- •New York Heart Association class II-IV heart disease
- •Congestive heart failure
- •Serious cardiac arrhythmia requiring medication
- 另有 71 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (enzyme inhibitor, monoclonal antibody)
Patients receive temsirolimus IV over 30 minutes on days 1 and 8 and bevacizumab IV over 30-90 minutes on day 8. Treatment repeats every 14 days for a maximum of 26 courses in the absence of disease progression or unacceptable toxicity. Patients undergo tumor resection on day 9 of course 2.
干预措施: Bevacizumab (Biological)
Treatment (enzyme inhibitor, monoclonal antibody)
Patients receive temsirolimus IV over 30 minutes on days 1 and 8 and bevacizumab IV over 30-90 minutes on day 8. Treatment repeats every 14 days for a maximum of 26 courses in the absence of disease progression or unacceptable toxicity. Patients undergo tumor resection on day 9 of course 2.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (enzyme inhibitor, monoclonal antibody)
Patients receive temsirolimus IV over 30 minutes on days 1 and 8 and bevacizumab IV over 30-90 minutes on day 8. Treatment repeats every 14 days for a maximum of 26 courses in the absence of disease progression or unacceptable toxicity. Patients undergo tumor resection on day 9 of course 2.
干预措施: Temsirolimus (Drug)
Treatment (enzyme inhibitor, monoclonal antibody)
Patients receive temsirolimus IV over 30 minutes on days 1 and 8 and bevacizumab IV over 30-90 minutes on day 8. Treatment repeats every 14 days for a maximum of 26 courses in the absence of disease progression or unacceptable toxicity. Patients undergo tumor resection on day 9 of course 2.
干预措施: Therapeutic Conventional Surgery (Procedure)
结局指标
主要结局
Objective Tumor Response (Complete Response and Partial Response) and Progression in Participants With Stage III or IV Melanoma Following Treatment With Temsirolimus and Bevacizumab
时间窗: Up to 18 weeks after registration.
Evaluated using Response Evaluation Criteria In Solid Tumor (RECIST) criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (POD); POD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions.
次要结局
- Adverse Events in Participants With Stage III or IV Melanoma Treated With Temsirolimus and Bevacizumab(On days 1 and 8 of each cycle, and up to 2 years after registration.)
- Association Between Expression or Activation of One Biomarker With Another, With Biochemical and Clinical Responses, With Alterations in Cell Proliferation and Apoptotic Markers, and With Time to Progression(Day 1 of course 1 and day 8 of course 2)
- Comparison of Biomarkers to Antitumor Activity/Patient Outcomes(Day 1 of course 1 and day 8 of course 2)
- Comparison of Pre- vs Post-treatment Measurements of Biomarkers and Vascular System/Immune System Parameters(Day 1 of course 1 and day 8 of course 2)
- Progression-free Survival(Day 11 of courses 4, 8, 12, 16, 20, and 24, and then annually for up to 5 years)