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Dose Intensification Study in Refractory Germ Cell Tumors With Relapse and Bad Prognosis (TICE)
This study is currently recruiting participants.
Verified by Institut Claudius Regaud, March 2009
First Received: March 16, 2009   Last Updated: March 17, 2009   History of Changes
Sponsor: Institut Claudius Regaud
Information provided by: Institut Claudius Regaud
ClinicalTrials.gov Identifier: NCT00864318
  Purpose

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 Intervention Phase
Germ Cell Tumors
Drug: Paclitaxel
Drug: Ifosfamide
Drug: Carboplatine
Drug: Etoposide
Procedure: cytapheresis + transfusion of autologous peripheral blood stem cells
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label, Single Group Assignment, Efficacy Study
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.

Resource links provided by NLM:


Further study details as provided by Institut Claudius Regaud:

Primary Outcome Measures:
  • Complete response rate(by chemotherapy or chemotherapy + surgery), pathological complete response rate. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression free survival [ Time Frame: 8 years ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: 8 years ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Etoposide pharmacokinetics (in particular inter-individual variability of Etoposide plasmatic concentrations AUC in such patients [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Genetic polymorphisms involved in response and safety treatments [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 93
Study Start Date: March 2009
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Paclitaxel
    200mg/m2 for 3 hours at Cycle 1 day 1 and Cycle 2 day 1 with 14 days between cycles
    Drug: Ifosfamide
    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
    Drug: Carboplatine

    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

    Drug: Etoposide
    From Cycle 3 to cycle 5, 400mg/m2/day from day 1 to day 3
    Procedure: cytapheresis + transfusion of autologous peripheral blood stem cells

    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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00864318

Contacts
Contact: Christine CHEVREAU, MD +33 5 61 42 42 42 Chevreau.Christine@claudiusregaud.fr
Contact: Muriel POUBLANC + 33 5 61 42 46 74 Poublanc.Muriel@claudiusregaud.fr

Locations
France
CHU Not yet recruiting
Clermont Ferrand, France, 63003
Contact: Jacques-Olivier BAY, MD         jobay@chu-clermontferrand.fr    
Principal Investigator: Jacques-olivier BAY, MD            
Institut Bergonié Not yet recruiting
Bordeaux, France, 33076
Contact: Binh BUI, MD         bui@bergonie.org    
Principal Investigator: Binh BUI, MD            
Center Oscar Lambret Not yet recruiting
Lille, France, 59020
Contact: Armelle CATY, MD         a-caty@o-lambret.fr    
Principal Investigator: Armelle CATY, MD            
Centre Antoine Lacassagne Not yet recruiting
Nice, France, 06050
Contact: Antoine THYSS, MD         antoine.thyss@cal.nice.fnclcc.fr    
Principal Investigator: Antoine THYSS, MD            
Centre Léon Bérard Not yet recruiting
Lyon, France, 69373
Contact: Aude FLECHON, MD         flechon@lyon.fnclcc.fr    
Principal Investigator: Aude FLECHON, MD            
Centre Paul Papin Not yet recruiting
Angers, France, 49933
Contact: Rémy DELVA, MD         r.delva@unimedia.fr    
Principal Investigator: Rémy DELVA, MD            
Institut Claudius Regaud Recruiting
Toulouse, France, 31052
Contact: Christine Chevreau, MD     +33 5.59.42.41.18     Chevreau.Christine@claudiusregaud.fr    
Principal Investigator: Christine CHEVREAU, MD            
Hopital St André Not yet recruiting
Bordeaux, France, 33075
Contact: Alain RAVAUD, MD         alain.ravaud@chu-bordeaux.fr    
Principal Investigator: Alain RAVAUD, MD            
Institut Val d'aurelle Not yet recruiting
Montpellier, France, 34298
Contact: Damien POUESSEL, MD         damien.pouessel@valdorel.fnclc.fr    
Principal Investigator: Damien POUESSEL, MD            
Hopital TENON Not yet recruiting
Paris, France, 75970
Contact: Jean-Pierre Lotz, MD         jean-pierre.lotz@tnn.aphp.fr    
Principal Investigator: Jean-Pierre LOTZ, MD            
CHU Not yet recruiting
Strasbourg, France, 67091
Contact: Brigitte DUCLOS, MD         brigitte.duclos@chur-strasbourg.fr    
Principal Investigator: Brigitte DUCLOS, MD            
IGR Not yet recruiting
Villejuif, France, 94805
Contact: Karim FIZAZI, MD         karim.fizazi@igr.fr    
Principal Investigator: Karim FIZAZI, MD            
hopital Mondor Not yet recruiting
Créteil, France, 94010
Contact: Stéphane CULINE, MD         stephane.culine@hmn.aphp.fr    
Principal Investigator: Stéphane CULINE, MD            
Institut Paoli Calmette Not yet recruiting
Marseille, France, 13273
Contact: Gwenaëlle GRAVIS, MD         gravisg@marseille.fnclcc.fr    
Principal Investigator: Gwenaelle GRAVIS, MD            
Sponsors and Collaborators
Institut Claudius Regaud
Investigators
Principal Investigator: Christine CHEVREAU, MD Institut Claudius Regaud
  More Information

No publications provided

Responsible Party: Institut Claudius Regaud ( Dr Christine CHEVREAU )
Study ID Numbers: 08 GENH 06
Study First Received: March 16, 2009
Last Updated: March 17, 2009
ClinicalTrials.gov Identifier: NCT00864318     History of Changes
Health Authority: France: Afssaps - French Health Products Safety Agency

Keywords provided by Institut Claudius Regaud:
refractory
germ cell tumors
relapse
bad prognosis
Refractory germ cell tumors with relapse and bad prognosis

Additional relevant MeSH terms:
Disease Attributes
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Mitosis Modulators
Antimitotic Agents
Etoposide phosphate
Pharmacologic Actions
Recurrence
Neoplasms
Ifosfamide
Pathologic Processes
Paclitaxel
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Tubulin Modulators
Antineoplastic Agents, Alkylating
Alkylating Agents
Etoposide
Antineoplastic Agents, Phytogenic
Isophosphamide mustard

ClinicalTrials.gov processed this record on February 08, 2010