A Phase II Study of Nilotinib (AMN107) In TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral or Chronically Sun Damaged Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 8
- 主要终点
- 4-month Progression-Free Survival Rate
研究概览
简要总结
Given the poor prognosis and limited treatment options available for patients with mucosal or acral/lentiginous melanomas who develop metastatic disease, genetic discoveries of KIT mutations in these cancers present the need to test multi-targeted kinase inhibitors with potent KIT inhibitory activity in this patient population. Imatinib and other tyrosine kinase inhibitors (TKIs) have the potential to be effective in this patient population, but patients may develop resistance to treatment. Therefore, in this study, we propose to test nilotinib in patients with metastatic mucosal, acral, or chronically sun-damaged melanoma following treatment with another TKI.
详细描述
OBJECTIVES:
Primary
* To estimate the proportion of patients, with metastatic mucosal, acral, or chronically sun damaged melanomas, whose tumors have KIT aberrations, and who progressed or could not tolerate a KIT targeting tyrosine kinase inhibitor (TKI) (e.g. including but not limited to imatinib mesylate, sunitinib, or dasatanib), who are alive and without progression of disease four months after beginning treatment with nilotinib.
Secondary
- To determine early evidence of biologic and clinical activity by best overall response rate.
- To estimate time to progression of disease and overall survival.
- To determine the tolerability of nilotinib.
- To evaluate the use of FDG-PET scanning in determining early biologic response to therapy.
- To correlate c-kit mutational status and amplification status with response to therapy.
- To evaluate the feasibility of nilotinib.
- To evaluate the tolerability of nilotinib in patients with brain metastases.
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
- •18 years of age or older
- •Histologically documented diagnosis of mucosal melanoma or acral melanoma or chronically sun damaged melanoma as evidenced by solar elastosis on pathology
- •Patient's tumor with evidence for KIT mutation or amplification. Patient tumors that already have documented mutations or amplification do not have to have tissue submitted again for analysis to confirm eligibility
- •Have failed, progressed, or not been able to tolerate other tyrosine kinase inhibitors including but not limited to imatinib mesylate, sunitinib or dasatinib treatment.
- •At least one measurable site of disease
- •ECOG Performance Status 0, 1 or 2
- •Adequate organ function as outlined in the protocol
- •Negative pregnancy test for female patients of childbearing potential
排除标准
- •Patient has received any other investigational agents within 28 days of first day of study drug dosing unless the disease is rapidly progressing
- •Patient is < 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 a cervical carcinoma in situ
- •Female patients who are pregnant or breast-feeding
- •Patient has a severe and/or uncontrolled medical disease
- •Patient has a rare hereditary problem of galactose intolerance, severe lactase deficiency or of glucose-galactose malabsorption
- •Patient with electrolyte abnormality unless the level can be corrected to normal levels prior to initiating study drug
- •Known brain metastasis
- •Known chronic liver disease
- •Patient has received chemotherapy within 4 weeks prior to study entry, unless the disease is rapidly progressing (6 weeks for nitrosourea or mitomycin-C)
- •Patient previously received radiotherapy to 25% or greater of the bone marrow
- •Patient had a major surgery within 2 weeks prior to study entry
- •Impaired cardiac function
- •QTc > 450msec on screening ECG
- •Myocardial infarction within one year prior to starting nilotinib
- •Other clinically significant heart disease
- •Patients who are currently receiving treatment with any of the medications that have the potential to prolong QT interval
- •Patients who are currently receiving Warfarin > 1mg/day
- •Patient with any significant history of non-compliance to medical regimens or with the inability to grant reliable informed consent
- •Prior therapy with nilotinib
研究组 & 干预措施
Nilotinib
Nilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit.
干预措施: Nilotinib (Drug)
结局指标
主要结局
4-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 4 months.
4-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 4 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
- Progression-Free Survival(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 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m).)
- Overall Survival(Patients were followed long-term every 3 months until first progression, death or lost to follow-up. Median survival follow-up was 16.2 months (90%CI 11.7-17.7 months; no/with CNS mets 16.2m/ 11.7m).)
- Best Overall Response(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 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m).)
研究者
F. Stephen Hodi, MD
Melanoma Disease Center Director
Dana-Farber Cancer Institute