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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Institut Claudius Regaud
Sponsor:
Information provided by (Responsible Party):
Institut Claudius Regaud
ClinicalTrials.gov Identifier:
NCT00864318
First received: March 16, 2009
Last updated: September 10, 2014
Last verified: September 2014
  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 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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.

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: September 2029
Estimated Primary Completion Date: September 2021 (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
    Other Name: Taxol
    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
    Other Name: Holoxan
    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
    Other Name: VP16
    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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Centre Paul Papin Recruiting
Angers, France, 49933
Contact: Rémy DELVA, MD       r.delva@unimedia.fr   
Principal Investigator: Rémy DELVA, MD         
Institut Bergonié Not yet recruiting
Bordeaux, France, 33076
Contact: Nadine HOUEDE, MD    05 56 33 33 44 ext +33      
Principal Investigator: Nadine HOUEDE, MD         
Hopital St André Recruiting
Bordeaux, France, 33075
Contact: Marine GROSS-GOUPIL, MD    05 56 79 58 08 ext +33      
Principal Investigator: Marine GROSS-GOUPIL, MD         
CHU Recruiting
Clermont Ferrand, France, 63003
Contact: Jacques-Olivier BAY, MD       jobay@chu-clermontferrand.fr   
Principal Investigator: Jacques-olivier BAY, MD         
Centre Léon Bérard Recruiting
Lyon, France, 69373
Contact: Aude FLECHON, MD       flechon@lyon.fnclcc.fr   
Principal Investigator: Aude FLECHON, MD         
Institut Paoli Calmette Recruiting
Marseille, France, 13273
Contact: Gwenaëlle GRAVIS, MD       gravisg@marseille.fnclcc.fr   
Principal Investigator: Gwenaelle GRAVIS, MD         
Institut Val d'aurelle Not yet recruiting
Montpellier, France, 34298
Contact: Diego TOSI, MD    04 67 61 31 52 ext +33      
Principal Investigator: Diego TOSI, MD         
Centre Antoine Lacassagne Recruiting
Nice, France, 06050
Contact: Antoine THYSS, MD       antoine.thyss@cal.nice.fnclcc.fr   
Principal Investigator: Antoine THYSS, MD         
Hopital TENON 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         
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         
Institut Gustave Roussy Recruiting
Villejuif, France, 94805
Contact: Karim FIZAZI, MD       karim.fizazi@igr.fr   
Principal Investigator: Karim FIZAZI, 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
ClinicalTrials.gov Identifier: NCT00864318     History of Changes
Other Study ID Numbers: 08 GENH 06
Study First Received: March 16, 2009
Last Updated: September 10, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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:
Neoplasms, Germ Cell and Embryonal
Neoplasms
Neoplasms by Histologic Type
Paclitaxel
Etoposide
Isophosphamide mustard
Ifosfamide
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 19, 2014