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

March 16, 2009
September 10, 2014
March 2009
September 2021   (final data collection date for primary outcome measure)
Complete response rate(by chemotherapy or chemotherapy + surgery), pathological complete response rate. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00864318 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Dose Intensification Study in Refractory Germ Cell Tumors With Relapse and Bad Prognosis
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.

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.

Not Provided
Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Germ Cell Tumors
  • 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

Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
93
September 2029
September 2021   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
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
France
 
NCT00864318
08 GENH 06
Yes
Institut Claudius Regaud
Institut Claudius Regaud
Not Provided
Principal Investigator: Christine CHEVREAU, MD Institut Claudius Regaud
Institut Claudius Regaud
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP