Phase II Multicentric Uncontrolled National Trial Assessing the Efficacy of Nilotinib in First or Second Line Treatment of Primary Melanomas , Stage III Unresectable Melanomas, or Stage IV Melanomas With c-KIT Mutation or Amplification.
试验速览
- 阶段
- 2 期
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Objective response
研究概览
简要总结
NILOMEL is a phase II multicentric uncontrolled open national trial assessing the efficacy of Nilotinib in first or second line treatment of primary melanomas , stage III unresectable melanomas, or Stage IV melanomas with c-KIT mutation or amplification. The primary objective is overall response rate (partial and complete response) according to RECIST 1.1 criteria, assessed using CT-SCAN (stage IV melanoma) or MRI (unresectable melanoma) after 6 months therapy with Nilotinib 800 mg/d. Secondary objectives include:
- Disease control rate (complete, partial response and stable disease)
- Metabolic response
- Tolerance NCI CTCAE Version 3.0
- Biomarkers associated to response and disease control.
详细描述
NILOMEL is a phase II multicentric uncontrolled open national trial assessing the efficacy of Nilotinib in first or second line treatment of primary melanomas , stage III unresectable melanomas, or Stage IV melanomas with c-KIT mutation or amplification (in case of c-KIT amplification, no B-RAF nor N-Ras mutation should be detected). The primary objective is overall response rate (partial and complete response) according to RECIST 1.1 criteria, assessed using CT-SCAN (stage IV melanoma) or MRI (unresectable melanoma) after 6 months therapy with Nilotinib 800 mg/d. Secondary objectives include:
- Disease control rate (complete, partial response and stable disease) according to RECIST
- Metabolic response rate (TEP-SCAN)
- Tolerance NCI CTCAE Version 3.0
- Biomarkers associated to response and disease control (evaluated at M0, M1 and M6). Protein analysis of c-KIT, PI3K, MAPK and STAT signalling pathways as well as PDGFR and Ephrin signalling pathways.
Patients with progressive disease after 3 months therapy will be withdrawn. Patient with stable disease after 3 months will continue Nilotinib until evaluation at 6 months. Patients with stable disease or progressive disease at 6 months will continue Nilotinib until progression.
The trial has been planned using a one-stage design (Fleming TR) . We considered that a response rate under 7.5% would define the null hypothesis of no efficacy . To detect a response rate of 30% or more with power 90% using a one-sided test at the 0.05 level, 25 patients have to be recruited.
Accrual for 2.5 years total study duration: 3 years
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
- •Patients with histologically proven melanoma with either c-KIT mutation or C-KIT amplification (without BRAF or NRAS mutation)
- •Unresectable primary or stage III or stage IV melanoma
- •Measurable disease (RECIST)
- •The inclusion of patients with primary tumor or metastasis accessible to sequential biopsies will be favored. If such lesions are present, biopsies are mandatory and not optional
- •No more than 1 previous specific therapy excluding tyrosine kinase inhibitors. 4 weeks wash out will be needed after cytotoxic therapy , 12 weeks wash out after anti -CTLA4 therapy or any immunological treatment
- •No radiotherapy within 4 weeks ; previously irradiated lesion will not be considered as measurable unless progression at inclusion
- •ECOG performance status < 2
- •WBC ≥ 3,000/mm³
- •PNN ≥ 1,500/mm³ (G-CSF allowed)
- •platelets ≥ 100,000/mm³
- •Hb ≥ 9.0 g/dL ( transfusions allowed as well as recombinant erythropoetin)
- •Creatinin clearance > 40ml/mn
- •Normal kalemia
- •Normal magnesemia
- •Total bilirubin <1.5N ; ASAT and ALAT <2.5N
- •PT/INR and PTT normal
- •NYHA class < 3
- •Signed Written Informed Consent
- •Affiliated to the National Health Insurance
排除标准
- •Patients refusal
- •Age < 18 years
- •Fertile women who do not want or cannot use effective contraception during the study and up to 8 weeks after the end of study
- •Women pregnant or nursing
- •Women with positive pregnancy test at inclusion or before treatment initiation
- •Fertile and sexually active men whose partner are fertile women who do not use effective contraception
- •Clinical and/or radiographic evidence of active cerebral metastases
- •Severe evolutive infection
- •Known HIV infection
- •Concomitant therapy with any other anti-cancer, immunomodulator or immunosuppressing agent or radiotherapy (except palliative care if bone metastases, after acceptance of principal investigator).
- •Previous use of tyrosine kinase inhibitors
- •More than one line of prior systemic therapies of melanoma by anti-cancer agent or immunotherapy.
- •Received experimental treatment within 4 weeks of inclusion
- •Pace-maker
- •Cardiac dysfunction, as evaluated by one of:
- •Ejection fraction < 45% (less than 28 days from inclusion)
- •Congenital prolonged QT
- •QTc > 450 ms
- •Ventricular tachyarrhythmia within the past 6 months
- •Bradycardia at rest < 50/mn
- •Major conduction dysfunction
- •Myocardial infarction within the previous 6 months
- •Unstable angina
- •Uncontrolled hypertension
- •Digestive disease that may inhibited NILITINIB absorption
- •Concomitant medication that may increase QT
- •Taking CYP3A4 inhibitors
- •Eating Sevilla oranges (or Sevilla oranges derivates), grapefruit (or grapefruit juice), grapes (or grapes juice), pomegranate (or pomegranate juice)
- •Hereditary galactose intolerance, Lapp-lactase deficiency or glucose-galactose malabsorption.
研究组 & 干预措施
Nilotinib
干预措施: Nilotinib (Drug)
结局指标
主要结局
Objective response
时间窗: 6 months
Partial or complete response per Response Evaluation Criteria in Solid Tumors (RECIST).
次要结局
- Disease control(6 months)
- Objective response(3 months)
- Metabolic response(6 months)
- Tolerance(1 year)