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

NCT ID: NCT01168050

Last Updated: 2011-02-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2013-12-31

Brief 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.

Detailed Description

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Patients with progressive disease after 3 months therapy will be withdrawn.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

Conditions

Malignant Skin Melanoma T0; Stage III Melanoma; Stage IV Melanoma; Amplification

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nilotinib

Group Type: EXPERIMENTAL

Nilotinib

Intervention Type: DRUG

Nilotinib 400 mg twice per day

Interventions

Nilotinib

Nilotinib 400 mg twice per day

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Department Clinical Research of Developpement

Principal Investigators

Celeste Lebbe, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Saint-Louis, Paris, France

Locations

Hôpital Saint-Louis

Paris, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Zakia Idir, PhD

Role: CONTACT

zakia.idir@sls.aphp.fr

+33 1 4484 1747

Facility Contacts

Celeste Lebbe, MD, PhD

Role: primary

celeste.lebbe@sls.aphp.fr

Other Identifiers

P081237

Identifier Type: -

Identifier Source: org_study_id