A Phase II Study of SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 5
- 主要终点
- 2-month Progression-free Survival Rate
研究概览
简要总结
The purpose of this study is to evaluate how effective Sunitinib works in treating acral lentiginous and mucosal melanoma which has spread beyond the local region. Suninitib is a protein-tyrosine kinase inhibitor and acts as a c-kit inhibitor drug. It is believed to work by blocking signals on certain cancer cells which allow the malignant cells to multiply and spread due to a change in the genetic make up of the cancer cell.
详细描述
OBJECTIVES:
Primary
- To determine the proportion of participants with metastatic mucosal or acral/lentiginous melanoma who are alive and without disease progression at two months after beginning treatment with sunitinib.
- To determine the best overall response rate.
Secondary
- To determine the time to progression and overall survival.
- To correlate c-kit mutational status with response to therapy.
- To evaluate the use of FDG-PET scanning in determining early biologic response to therapy.
- To assess amplification of c-kit status through quantitative PCR and/or FISH and other related molecular pathway targets.
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
- •History of primary mucosal or acral/lentiginous melanoma
- •Histologically documented stage III unresectable or IV metastatic melanoma
- •ECOG Performance Status 0,1 or 2
- •Estimated life expectancy of 6 months or greater
- •18 years of age or older
- •Lab values as outlined in protocol
- •Tumor blocks or slides must be available of either primary or metastatic tumor site for c-kit mutation testing
- •Negative pregnancy test within 48 hours of starting treatment
- •At least one measurable site of disease as defined by at least 1cm in greatest dimension
排除标准
- •Severe and/or uncontrolled medical disease
- •Pregnant or nursing mothers
- •Known brain metastasis. History of or known spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening CT or MRI scan
- •Less than 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or cervical carcinoma in situ
- •Grade III/IV cardiac problems as defined by the New York Heart Association Criteria
- •Ongoing cardiac dysrhythmias of grade 2 or greater, atrial fibrillation, QTc interval >450msec for males of >470 msec for females
- •Hypertension that cannot be controlled by medication
- •Any of the following within 12 months prior to starting treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism
- •NCI CTCAE version 3.0 grade 3 hemorrhage within 4 weeks of starting the study treatment
- •Concurrent treatment with warfarin
- •Prior treatment with SU011248 or any other antiangiogenic agent
- •No H2 blockers or proton pump inhibitors
- •Known chronic liver disease
- •Known HIV infection
- •Previous radiotherapy to 25% or more of the bone marrow and/or radiation therapy within 4 weeks prior to study entry
- •Major surgery within 4 weeks prior to study entry
- •Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
研究组 & 干预措施
Sunitinib
Cohort A participants received 50 mg sunitinib orally daily for 4 weeks followed by a two-week break from treatment. These 6-week cycles would be repeated until progression or unacceptable toxicity up to 1 year.
Cohort B participants received 37.5 mg sunitinib daily on a continuous basis until progression or unacceptable toxicity up to 1 year.
干预措施: Sunitinib (Drug)
结局指标
主要结局
2-month Progression-free Survival Rate
时间窗: Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued for 12 months unless disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 2 months.
2-month progression-free survival rate was defined as the proportion of patients absent death or progression based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST) before 2 months. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (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. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
次要结局
- Best Overall Response Rate(Disease was evaluated radiologically at baseline and every 8 weeks on treatment. Mean treatment duration was 3 cycles (Cohort A/B mean 2/3 cycles). The range of treatment duration overall was 1-11 cycles.)
- Overall Survival(Patients were followed long-term every 3 months until first progression, death or lost to follow-up. Median survival follow-up was 6.7 months (range 0.8-47.3 months; Cohort A/B median 7.7 m/ 6.2 m).)
- Time to Progression(Disease was evaluated radiologically at baseline and every 8 weeks on treatment and long-term every 3 months until first progression, death or lost to follow-up. Mean treatment duration was 3 cycles (range 1-11; Cohort A/B mean 2/3 cycles).)
研究者
F. Stephen Hodi, MD
Melanoma Disease Center Director
Dana-Farber Cancer Institute