Not randomized, multicentric, national phase II trial estimating the efficacy of an intensification protocol in patients with refractory germ cell tumors with relapse and bad prognosis.

Treatment consists in two Paclitaxel and Ifosfamide intensification cycles followed by three Carboplatine and Etoposide high dose cycles. The point is the individual Carboplatine adjustment to take into account inter-individual patients variability.

This adaptation allow to control each patient plasmatic exposition to avoid both inacceptable toxicities (such as ear toxicity) and a low exposition losing then the benefit of this high dose protocol.

Inclusion Criteria:

1. Germ cell tumors whatever histology (TGNS or séminoma : TGS ) whose origin is gonadic, extra-gonadic, retro-peritoneal or primitive mediastinal

2. Age >= 18 years old

3. Histologically confirmed germ cell tumor (TGS) or biomarkers rate allowing to diagnose germ cell tumor without histology (TGNS)

4. 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.

5. TGNS or TGS in relapse after 2 treatment lines

6. 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

7. ECOG Performance status 0-2

8. 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

9. Cardiac Functions (FEV >= 50%), Respiratory Functions , neurological Functions compatibles with high dose chemotherapy administration

10. Absence of previous intensification

11. Patient Information and Informed consent signature

12. HIV and B and C hepatitis negative serologies

13. Negative pregnancy test for women with reproductive potential and adequate contraception before study entry

14. Patient affiliated to social security system

Exclusion Criteria:

1. Patients whose diagnosis of relapse was not confirmed by an anatomopathological examination or by an increase of tumors markers
2. Primitive encephalic germ cell tumors
3. 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
4. Growing Teratoma lesions
5. Patients with HIV infection, hepatitis B and C
6. Patients with symptomatic brain metastases despite appropriate corticosteroid treatment
7. Associated pathology may prevent the patient to receive treatment, creatinine clearance ≤ 50 mL / min (calculated by Cockcroft-Gault)
8. FEV <50%
9. History of cancer (except basal cell epithelioma skin cancer) in the 3 years preceding the entry into the trial
10. Patient already included in another clinical trial involving an experimental molecule
11. Pregnant or breast feeding women
12. Persons without liberty or under guardianship,
13. Geographical, social or psychological conditions that do not permit compliance with protocol