A Phase I/II Study Of Imatinib Mesylate And Bevacizumab In Patients With Advanced Melanoma And Other Advanced Cancers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- MTD, Defined as One Dose Level Below the Dose That Induced DLT in at Least One Third of Patients at a Dose Level, Graded According to NCI CTCAE Version 3.0 (Phase I)
研究概览
简要总结
Phase II trial to study the effectiveness of combining imatinib mesylate with bevacizumab in treating patients who have advanced melanoma or other metastatic or unresectable cancer. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Bevacizumab may stop the growth of tumor cells by stopping blood flow to the tumor. Combining imatinib mesylate with bevacizumab may kill more tumor cells
详细描述
OBJECTIVES:
I. Determine the tolerability, maximum tolerated dose, and lowest biologically active dose of imatinib mesylate and bevacizumab in patients with advanced melanoma or other advanced cancers.
II. Determine the response rate, time to progression, and survival of patients treated with this regimen.
III. Correlate clinical activity with inhibition of platelet-derived growth factor receptor beta, vascular endothelial growth factor receptor, flt-1, and markers of angiogenesis in patients treated with this regimen.
IV. Correlate clinical activity with alterations in tumor perfusion as assessed by dynamic contrast-enhanced MRI and Doppler ultrasound 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
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed diagnosis of 1 of the following:
- •Metastatic or unresectable malignancy for which standard curative or palliative measures do not exist or are no longer effective (phase I) (phase I study closed to accrual as of 8/23/04)
- •Melanoma (phase I and II)
- •Measurable disease (phase II)
- •No history or clinical evidence of CNS disease, including primary brain tumor or brain metastases
- •Performance status - ECOG 0-1
- •More than 3 months
- •WBC at least 3,000/mm^3
- •Absolute granulocyte count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •No history of bleeding diathesis or coagulopathy
- •Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- •AST and ALT no greater than 2.5 times ULN
- •INR no greater than 1.5
- •APTT normal
- •Creatinine no greater than 2.0 times ULN
- •Creatinine clearance at least 40 mL/min
- •No proteinuria
- •Urinary protein less than 500 mg/24 hours
- •No history of stroke
- •No uncontrolled hypertension within the past 6 months
- •Blood pressure less than 150/100 mm Hg on a stable antihypertensive regimen
- •None of the following within the past 6 months:
- •Myocardial infarction
- •Unstable angina
- •New York Heart Association class II-IV congestive heart failure
- •Serious cardiac arrhythmia requiring medication
- •Grade II or greater peripheral vascular disease
- •Transient ischemic attack
- •Cerebrovascular accident
- •Other arterial thromboembolic event
- •Other clinically significant cardiovascular disease
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective barrier contraception during and for at least 3 months after study participation
- •No seizures not controlled with standard medical therapy
- •No prior allergic reactions attributed to Chinese hamster ovary cell products, other recombinant human antibodies, or compounds of similar chemical or biological composition to imatinib mesylate
- •No serious, nonhealing wound, ulcer, or bone fracture
- •No ongoing or active infection requiring parenteral antibiotics
- •No significant traumatic injury within the past 28 days
- •No psychiatric illness or social situation that would preclude study compliance
- •No other concurrent uncontrolled illness
- •More than 4 weeks since prior immunotherapy
- •More than 8 weeks since prior monoclonal antibody therapy
- •No concurrent prophylactic granulocyte or platelet colony-stimulating factors
- •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- •No more than 1 prior cytotoxic chemotherapy regimen for advanced disease (phase II)
- •More than 4 weeks since prior radiotherapy
- •More than 28 days since prior major surgical procedure or open biopsy
- •Recovered from prior therapy
- 另有 7 项未显示
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive oral imatinib mesylate once or twice daily on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: imatinib mesylate (Drug)
Arm I
Patients receive oral imatinib mesylate once or twice daily on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: bevacizumab (Biological)
Arm I
Patients receive oral imatinib mesylate once or twice daily on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Arm I
Patients receive oral imatinib mesylate once or twice daily on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
MTD, Defined as One Dose Level Below the Dose That Induced DLT in at Least One Third of Patients at a Dose Level, Graded According to NCI CTCAE Version 3.0 (Phase I)
时间窗: Up to 28 days
Progression-free Survival at 16 Weeks (Phase II)
时间窗: 16 weeks
Progression Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
次要结局
- Response Rate at 8 Weeks, Evaluated Using RECIST (Phase II)(8 weeks)
- Overall Survival (Phase II)(Up to 6 years)