Dose Intensification Study in Refractory Germ Cell Tumors With Relapse and Bad Prognosis
TICE
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.
1 other identifier
interventional
101
1 country
12
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Mar 2009
Longer than P75 for phase_2
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 13, 2009
CompletedFirst Submitted
Initial submission to the registry
March 16, 2009
CompletedFirst Posted
Study publicly available on registry
March 18, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 5, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
October 5, 2020
CompletedApril 14, 2026
April 1, 2026
11.6 years
March 16, 2009
April 9, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Complete response rate(by chemotherapy or chemotherapy + surgery), pathological complete response rate.
6 months
Secondary Outcomes (6)
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
- +1 more secondary outcomes
Interventions
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
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
Eligibility Criteria
You may qualify if:
- 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
- +2 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (12)
Centre Paul Papin
Angers, 49933, France
Hopital St André
Bordeaux, 33075, France
Institut Bergonié
Bordeaux, 33076, France
CHU
Clermont-Ferrand, 63003, France
Centre Léon Bérard
Lyon, 69373, France
Institut Paoli Calmette
Marseille, 13273, France
Institut Val d'aurelle
Montpellier, 34298, France
Centre Antoine Lacassagne
Nice, 06050, France
Hopital TENON
Paris, 75970, France
CHU
Strasbourg, 67091, France
Institut Claudius Regaud
Toulouse, 31052, France
Institut Gustave Roussy
Villejuif, 94805, France
Related Publications (1)
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.
PMID: 33675184RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Christine CHEVREAU, MD
Institut Claudius Regaud
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 16, 2009
First Posted
March 18, 2009
Study Start
March 13, 2009
Primary Completion
October 5, 2020
Study Completion
October 5, 2020
Last Updated
April 14, 2026
Record last verified: 2026-04