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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
101
200mg/m2 for 3 hours at Cycle 1 day 1 and Cycle 2 day 1 with 14 days between cycles
2g/m²/day in 1 liter of G5 for 3 hours at Cycle 1 and Cycle 2 from day 2 to day 4 with 14 days between cycles
From cycle 3 to cycle 5 : Carboplatine is administered with AUC = 24 mg/mL x min from Day 1 to Day 3. Day 3 Carboplatine dose is calculated taking into account real creatinine clearance defined at day 1 for each patient
From Cycle 3 to cycle 5, 400mg/m2/day from day 1 to day 3
Cytapheresis occured between day 11 and day 13 of the 2 first cycle (Taxol® +Holoxan®). Cytapheresis total objective is 9X106 CD34+/kg of patient weight. At cycle 3, 4 and 5 at day 5 : Re-injection of stem cells (1/3 with minimum 2.106 CD34/kg) 48 hours after chemotherapy end
Centre Paul Papin
Angers, France
Hopital St André
Bordeaux, France
Institut Bergonié
Bordeaux, France
CHU
Clermont-Ferrand, France
Centre Léon Bérard
Lyon, France
Institut Paoli Calmette
Marseille, France
Institut Val d'aurelle
Montpellier, France
Centre Antoine Lacassagne
Nice, France
Hopital TENON
Paris, France
CHU
Strasbourg, France
...and 2 more locations
Complete response rate(by chemotherapy or chemotherapy + surgery), pathological complete response rate.
Time frame: 6 months
Progression free survival
Time frame: 8 years
Time to progression
Time frame: 8 years
Toxicity
Time frame: 6 months
To find a predictive value for Cystatin C as a biomarker of renal function to avoid next to follow plasmatic concentrations to adapt Carboplatine dose in TICE protocol.
Time frame: 4 years
Etoposide pharmacokinetics (in particular inter-individual variability of Etoposide plasmatic concentrations AUC in such patients
Time frame: 4 years
Genetic polymorphisms involved in response and safety treatments
Time frame: 4 years
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