Dose Intensification Study in Refractory Germ Cell Tumors With Relapse and Bad Prognosis

Inclusion criteria

• Germ cell tumors whatever histology (TGNS or séminoma : TGS ) whose origin is gonadic, extra-gonadic, retro-peritoneal or primitive mediastinal
• Age >= 18 years old
• Histologically confirmed germ cell tumor (TGS) or biomarkers rate allowing to diagnose germ cell tumor without histology (TGNS)
• Relapse or progression with bad prognosis in 1st treatment line : One of these criteria valid point 4 :

progression after incomplete clinical response (Stable disease) to a Cisplatin basis chemotherapy; biomarker progression 4 weeks following the last chemotherapy cycle administration; progression during the first treatment line without obtention of at least stable disease; primitive mediastinal origin in first relapse.

• TGNS or TGS in relapse after 2 treatment lines
• Disease progression ( previous points 4 or 5) documented by :

tumors biomarkers increase (AFP and/or HCG) if no, a biopsy is needed to confirm presence of tumors active cells

• ECOG Performance status 0-2
• Biological Function :

Neutrophils >= 1500/mm3, Platelets >= 150.000/mm3 ; normal creatinine (or clearance >= 50 ml/mn) ; SGOT, SGPT <= 2,5N (or 5N if hepatic metastases), Bilirubin < 1,5N

• Cardiac Functions (FEV >= 50%), Respiratory Functions , neurological Functions compatibles with high dose chemotherapy administration
• Absence of previous intensification
• Patient Information and Informed consent signature
• HIV and B and C hepatitis negative serologies
• Negative pregnancy test for women with reproductive potential and adequate contraception before study entry
• Patient affiliated to social security system

Exclusion criteria

• Patients whose diagnosis of relapse was not confirmed by an anatomopathological examination or by an increase of tumors markers
• Primitive encephalic germ cell tumors
• Germ cell tumors in relapse with favorable factors of treatment response to conventional chemotherapy (RC sustainable after Cisplatin): prior cRC or incomplete clinical response but with normalization of markers and testicular origin
• Growing Teratoma lesions
• Patients with HIV infection, hepatitis B and C
• Patients with symptomatic brain metastases despite appropriate corticosteroid treatment
• Associated pathology may prevent the patient to receive treatment, creatinine clearance ≤ 50 mL / min (calculated by Cockcroft-Gault)
• FEV <50%
• History of cancer (except basal cell epithelioma skin cancer) in the 3 years preceding the entry into the trial
• Patient already included in another clinical trial involving an experimental molecule
• Pregnant or breast feeding women
• Persons without liberty or under guardianship,
• Geographical, social or psychological conditions that do not permit compliance with protocol