Validation of a Treatment Algorithm for Poor-Risk NSGCTnon Seminomatous Germ-cell Tumors (VAPOR)

Inclusion Criteria: Male patient older than 16 years old on day of signing informed consent Patient with evidence of NSGCT based on histologic examination or based on clinical evidence and elevated serum hCG or AFP levels (in case of clinical emergency, therapy can be started before pathologic sample is obtained if tumor markers are highly elevated) Patient with testicular, retroperitoneal, or mediastinal primary site Patient with evidence of disseminated disease (clinical stages II or III according to AJCC 8th edition) Patient with disease classified as poor prognosis according to IGCCCG criteria: Primary mediastinal NSGCT or, Non-pulmonary visceral metastases or, hCG > 50 000 UI/L, or AFP > 10 000 ng/mL, or LDH > 10 times the upper normal value Patient with adequate renal function: measured or calculated (by Cockcroft formula) creatinine clearance > 60 mL/min. Cockcroft formula: CrCl = [(140-age) x weight in kg]/[72 x serum creatinine (mg/dL)] Patient with absolute granulocyte count > or = 1,500/mm^3, platelets > or = 100,000 mm^3, bilirubin < or = 1.5x the upper limit of normal value. Patient with a contra-indication of undergoing any brain MRI are eligible, but will not be part of the diagnostic study part Patient (and his legal guardian for under-18 patient) who had understood, signed and dated the informed consent form Patient affiliated to social security system or beneficiary of the same Male of child-bearing potential, must agree to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 6 months after the last treatment intake. Inclusion criteria specific to the phase 2 study in patients with unfavorable serum marker decrease and mediastinal primary tumor (to be confirmed before the end of the 1st BEP cycle) Patient (and his legal guardian for under-18 patient) who had understood, signed and dated the specific Phase II informed consent form Patient with mediastinal primary site Patient with unfavorable serum marker decrease evaluated at D18-D21 of the first BEP-chemotherapy Exclusion Criteria: Patient infected by the Human Immunodeficiency Virus (HIV) Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent Patient with prior chemotherapy. Patients who have received a first cycle of cisplatin-base chemotherapy (BEP) for their poor-prognosis NSGCT are eligible as far as tumor marker decline can be assessed at day 18-21. Patient with previous malignancy, except for basal-cell carcinoma of the skin Known allergy or hypersensitivity to any of the study drugs Non inclusion criteria specific to the phase 2 study in patients with unfavorable serum marker decrease and mediastinal primary tumor (to be confirmed before the end of the 1st BEP cycle) Patient (and his legal guardian for under-18 patient) who withdraws his consent Patient with Human T-cell Leukemia Virus (HTLV) type 1 and 2 Patient with Hepatitis B surface antigen Patient with Hepatitis C antibody Patient with prior high-dose chemotherapy (HDCT) plus hematopoietic stem cell HSCs transplant