A Phase 2 Study Evaluating the Efficacy of VEGF Trap in Patients With Recurrent Inoperable Stage III or Stage IV Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- 4 Month Progression-free Survival
研究概览
简要总结
This phase II trial is studying how well VEGF Trap works in treating patients with recurrent stage III or stage IV melanoma that cannot be removed by surgery. Combinations of biological substances in VEGF Trap may be able to carry tumor-killing substances directly to melanoma cells. It may also stop the growth of melanoma by blocking blood flow to the tumor.
详细描述
PRIMARY OBJECTIVES:
I. Determine the antitumor response rate (complete and partial response) in patients with recurrent inoperable stage III or IV melanoma treated with VEGF Trap.
II. Compare the progression-free survival of patients treated with this regimen vs historical controls.
SECONDARY OBJECTIVES:
I. Determine the overall survival of patients treated with this regimen. II. Determine the toxicity and tolerability of this regimen in these patients. III. Determine the impact of this regimen on laboratory correlates including anti-VEGF Trap antibody testing and pharmacokinetics in these patients.
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 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed stage III or IV melanoma
- •Cutaneous, ocular, or mucosal melanoma allowed
- •Recurrent, inoperable disease
- •Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
- •No evidence of CNS disease, including primary brain tumor or brain metastases
- •No brain metastases by MRI or CT scan within the past 4 weeks
- •ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- •Life expectancy > 3 months
- •WBC ≥ 3,000/mm³
- •Absolute neutrophil count ≥ 1,500/mm³
- •Platelet count ≥ 75,000/mm³
- •Bilirubin < 1.5 times upper limit of normal (ULN)
- •AST and ALT ≤ 2.5 times ULN
- •Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
- •Urine protein:creatinine ratio < 1 OR urine protein < 500 mg by 24-hour urine collection
- •PT INR ≤ 1.5 unless on full-dose warfarin
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
- •No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- •No history of allergic reactions attributed to compounds of similar chemical or biological composition to agents used in the study
- •No serious or nonhealing wound, ulcer, or bone fracture
- •No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
- •No significant traumatic injury within the past 28 days
- •No clinically significant cardiovascular disease, including any of the following:
- •Cerebrovascular accident within the past 6 months
- •Uncontrolled hypertension, defined as blood pressure (BP) > 150/100 mm Hg or systolic BP > 180 mm Hg if diastolic BP < 90 mm Hg within the past 3 months
- •Myocardial infarction, coronary artery bypass graft, or unstable angina within the past 6 months
- •New York Heart Association class III-IV congestive heart failure
- •Serious cardiac arrhythmia requiring medication
- •Unstable angina pectoris within the past 6 months
- •Clinically significant peripheral vascular disease within the past 6 months
- •Pulmonary embolism, deep vein thrombosis, or other thromboembolic event within the past 6 months
- •No evidence of bleeding diathesis or coagulopathy
- •No concurrent uncontrolled illness, including, but not limited to any of the following:
- •Ongoing or active infection
- •Psychiatric illness or social situation that would preclude study compliance
- •Recovered from all prior therapy and major surgery
- •No prior chemotherapy or hormonal therapy
- •More than 7 days since prior core visceral organ biopsy
- •More than 4 weeks since prior biologic therapy or radiotherapy
- •More than 28 days since prior major surgery or open biopsy
- •No concurrent major surgery
- •No other concurrent investigational agents
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •Concurrent full-dose warfarin with PT INR > 1.5 allowed provided the following criteria are met:
- •INR in range (2-3) on a stable dose of oral anticoagulant or low molecular weight heparin
- •No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive Aflibercept IV at 4 mg/kg over 1 hour on day 1. Treatment repeats every 14 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Arm I
Patients receive Aflibercept IV at 4 mg/kg over 1 hour on day 1. Treatment repeats every 14 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: ziv-aflibercept (Biological)
结局指标
主要结局
4 Month Progression-free Survival
时间窗: 4 months
Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 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.
Objective Response Rate (CR + PR)
时间窗: Start of treatment to disease progression/recurrence, up to 5 years
Using the RECIST v1.0 criteria for target lesions assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response = CR + PR.",
次要结局
- Number of Participants With Toxicities(Up to 5 years)
- Overall Survival(From the initial date of treatment to the recorded date of death, assessed up to 5 years)
- Impact of the VEGF Trap Therapy on Laboratory Correlates(Up to 5 years)