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

Sponsor

Institut Claudius Regaud (Other)

Overall Status

Completed

CT.gov ID

NCT00864318

Collaborator

(none)

101

Enrollment

Locations

138.8

Actual Duration (Months)

8.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Germ Cell Tumors	Drug: Paclitaxel Drug: Ifosfamide Drug: Carboplatine Drug: Etoposide Procedure: cytapheresis + transfusion of autologous peripheral blood stem cells	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

101 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Dose Intensification Phase II Study in Refractory Germ Cell Tumors With Relapse and Bad Prognosis. TICE Protocol : Paclitaxel and Ifosfamide Followed by Carboplatine and Etoposide Intensification With Individual Carboplatine Dose Adjustment.

Actual Study Start Date :

Mar 13, 2009

Actual Primary Completion Date :

Oct 5, 2020

Actual Study Completion Date :

Oct 5, 2020

Outcome Measures

Primary Outcome Measures

Complete response rate(by chemotherapy or chemotherapy + surgery), pathological complete response rate. [6 months]

Secondary Outcome Measures

Progression free survival [8 years]
Time to progression [8 years]
Toxicity [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. [4 years]
Etoposide pharmacokinetics (in particular inter-individual variability of Etoposide plasmatic concentrations AUC in such patients [4 years]
Genetic polymorphisms involved in response and safety treatments [4 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Centre Paul Papin	Angers	France	49933
2	Hopital St André	Bordeaux	France	33075
3	Institut Bergonié	Bordeaux	France	33076
4	CHU	Clermont Ferrand	France	63003
5	Centre Léon Bérard	Lyon	France	69373
6	Institut Paoli Calmette	Marseille	France	13273
7	Institut Val d'aurelle	Montpellier	France	34298
8	Centre Antoine Lacassagne	Nice	France	06050
9	Hopital TENON	Paris	France	75970
10	CHU	Strasbourg	France	67091
11	Institut Claudius Regaud	Toulouse	France	31052
12	Institut Gustave Roussy	Villejuif	France	94805