Efficacy of Nilotinib in First or Second Line Treatment of Primary Melanomas Stage III Unresectable Melanomas.

• Status: Unknown status
• Trial end date: 2013-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.