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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00864318
Recruitment Status : Completed
First Posted : March 18, 2009
Last Update Posted : January 12, 2021
Information provided by (Responsible Party):
Institut Claudius Regaud

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

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Study Type : Interventional  (Clinical Trial)
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 : March 13, 2009
Actual Primary Completion Date : October 5, 2020
Actual Study Completion Date : October 5, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Ifosfamide

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

Primary Outcome Measures :
  1. Complete response rate(by chemotherapy or chemotherapy + surgery), pathological complete response rate. [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Progression free survival [ Time Frame: 8 years ]
  2. Time to progression [ Time Frame: 8 years ]
  3. Toxicity [ Time Frame: 6 months ]
  4. 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 ]
  5. Etoposide pharmacokinetics (in particular inter-individual variability of Etoposide plasmatic concentrations AUC in such patients [ Time Frame: 4 years ]
  6. Genetic polymorphisms involved in response and safety treatments [ Time Frame: 4 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00864318

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Centre Paul Papin
Angers, France, 49933
Hopital St André
Bordeaux, France, 33075
Institut Bergonié
Bordeaux, France, 33076
Clermont Ferrand, France, 63003
Centre Léon Bérard
Lyon, France, 69373
Institut Paoli Calmette
Marseille, France, 13273
Institut Val d'aurelle
Montpellier, France, 34298
Centre Antoine Lacassagne
Nice, France, 06050
Hopital TENON
Paris, France, 75970
Strasbourg, France, 67091
Institut Claudius Regaud
Toulouse, France, 31052
Institut Gustave Roussy
Villejuif, France, 94805
Sponsors and Collaborators
Institut Claudius Regaud
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Principal Investigator: Christine CHEVREAU, MD Institut Claudius Regaud
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Institut Claudius Regaud Identifier: NCT00864318    
Other Study ID Numbers: 08 GENH 06
First Posted: March 18, 2009    Key Record Dates
Last Update Posted: January 12, 2021
Last Verified: January 2021
Keywords provided by Institut Claudius Regaud:
germ cell tumors
bad prognosis
Refractory germ cell tumors with relapse and bad prognosis
Additional relevant MeSH terms:
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Neoplasms, Germ Cell and Embryonal
Disease Attributes
Pathologic Processes
Neoplasms by Histologic Type
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Alkylating
Alkylating Agents