Phase 2 Study Assessing Efficacy and Safety of Crizotinib in Patients Harboring an Alteration on ALK, MET or ROS1

Inclusion criteria

Inclusion: * Male and female ≥ 1 year of age * unresectable locally advanced or metastatic malignant tumor of any histological type (but NSCLC with an ALK translocation) and not amenable to any other validated therapeutic option. ( for pediatrics a relapse after a first well-conducted standard treatment or a situation without any standard treatment and a survival \<10%). * one proven specific alterations among ALK, MET, RON and ROS1 genes determined on the primary and/or the metastatic lesion * Measurable disease according to RECIST 1.1 * For patients with primary cerebral tumors (adults or children), measurable disease defined by bi-dimensional measurements : two perpendicular diameters of at least 10 mm on CT or MRI scan, outside of a previously radiated field within the last 3 months, to observe pseudoprogression * hematologic function (ANC ≥ 1.0x10⁹/L, platelets ≥ 75x10⁹/L, platelets ≥ 50x10⁹/L for ALCL with bone marrow involved ; platelets ≥ 100x10⁹/L for primary or secondary cerebral tumors; Hb ≥ 8g/L), renal function (creat cl ≥ 50 mL/min Cockcroft and Gault) and hepatic function (serum bilirubin ≤ 1.5x ULN unless due to Gilbert's syndrome ; ASAT and ALAT ≤ 5x ULN if liver metastasis or ≤ 3x ULN if liver metastasis with advanced fibrosis (FibroTest\>0.48) or ≤ 3x ULN without liver metastasis) * normal values for calcium, magnesium and potassium levels * able to swallow and retain oral medication * ECOG Performance Status of 0 to 2, or Karnofsky scale \> 50 % or Lansky Play scale (\< 12 years) \> 50%, (for CNS tumors, the neurological deficiency due to the disease itself) * Life expectancy ≥ 3 months Exclusion : * NSCLC patients ALK translocations * Patient eligible for a clinical trial with an anticancer drug (including crizotinib) targeting the same molecular alteration open to accrual in France. * alteration limited to an overexpression of ALK, MET, RON, ROS1 or any other crizotinib-target. Only patients with ALCL are eligible if ALK is positive by immunohistochemistry * Patients with primary or secondary central nervous system disease * Previous treatment with crizotinib * Major surgery or tumor embolization within 4 weeks and minor surgery within 2 weeks prior to the initiation of the study drug. Brain surgery is excluded within 4 weeks prior to starting crizotinib for primary or secondary cerebral tumors * Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as, but not limited to : * Within the 3 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, or cerebrovascular accident including transient ischemic attack * Ongoing congestive heart failure * Congenital long QT syndrome * Heart rate ≤ 45 beats/minute * Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, uncontrolled atrial fibrillation of any grade, or with QTcF interval \>470 msec * For patients with a cerebral disease (primary or secondary) : uncontrolled hypertension \[defined as SBP of ≥ 140 mmHg or DBP of ≥ 90mmHg\] * extensive disseminated/bilateral or known presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease, including pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis, but not prior radiation pneumonitis * Spinal cord compression unless treated with the patient attaining good pain control and stable or recovered neurologic function * Carcinomatous meningitis or leptomeningeal disease * HIV-positive, active hepatitis A, B or C, or latent hepatitis B or C, or any other uncontrolled infection * Other severe acute or chronic medical or psychiatric conditions, or end stage renal disease on hemodialysis or laboratory abnormalities * For patients with a cerebral disease, detection on the MRI or the CTscan of a real arteriovenous malformation, or an untreated intracranial aneurysm, or a cavernous angioma, or an amyloid angiopathy, or any new or significant (≥ grade 2) intratumoral bleeding other than microbleeds on T2\* weighted MRI in the previous 14 days before treatment initiation, or a recent and untreated subdural effusion. * Patients using non-substitutable drugs that are potent CYP3A4 inhibitors, or potent CYP3A4 inducers * Patients using non-substitutable drugs that are CYP3A4 substrates with narrow therapeutic indices * Patients with cerebral disease using anti-platelet drugs or anticoagulant agents are not eligible if those treatments can not be stopped 7 days before day1. * Patients with altered mental status or with psychological, familial, sociological or geographical condition potentially hampering compliance * Individual deprived of liberty or placed under the authority of a tutor.