Clinical trial NCT00864318: Dose Intensification Study in Refractory Germ Cell Tumors With Relapse and Bad Prognosis
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Germ Cell Tumors
Keywords: refractory
germ cell tumors
relapse
bad prognosis
Refractory germ cell tumors with relapse and bad prognosis
Lead sponsor: Institut Claudius Regaud
Sponsor class: OTHER
First posted: 2009-03-18
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Complete response rate(by chemotherapy or chemotherapy + surgery), pathological complete response rate.
timeFrame: 6 months
Secondary outcomes:
measure: Progression free survival
timeFrame: 8 years
measure: Time to progression
timeFrame: 8 years
measure: Toxicity
timeFrame: 6 months
measure: 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.
timeFrame: 4 years
measure: Etoposide pharmacokinetics (in particular inter-individual variability of Etoposide plasmatic concentrations AUC in such patients
timeFrame: 4 years
measure: Genetic polymorphisms involved in response and safety treatments
timeFrame: 4 years
Other outcomes:
Locations:
city: Angers
country: France
facility: Centre Paul Papin
city: Bordeaux
country: France
facility: Hopital St André
city: Bordeaux
country: France
facility: Institut Bergonié
city: Clermont Ferrand
country: France
facility: CHU
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Montpellier
country: France
facility: Institut Val d'aurelle
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Hopital TENON
city: Strasbourg
country: France
facility: CHU
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Institut Claudius Regaud
name: Christine CHEVREAU, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chevreau C, Massard C, Flechon A, Delva R, Gravis G, Lotz JP, Bay JO, Gross-Goupil M, Fizazi K, Mourey L, Paci A, Guitton J, Thomas F, Lelievre B, Ciccolini J, Moeung S, Gallois Y, Olivier P, Culine S, Filleron T, Chatelut E. Multicentric phase II trial of TI-CE high-dose chemotherapy with therapeutic drug monitoring of carboplatin in patients with relapsed advanced germ cell tumors. Cancer Med. 2021 Apr;10(7):2250-2258. doi: 10.1002/cam4.3687. Epub 2021 Mar 5.