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

Germ Cell Tumors Clinical Trial

— TICE  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00864318
• Other study ID #: 08 GENH 06
• Status: Completed
• Phase: Phase 2
• Start date: March 13, 2009
• Est. completion date: October 5, 2020

Study information

• Verified date: January 2021
• Source: Institut Claudius Regaud
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: October 5, 2020
• Est. primary completion date: October 5, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Germ Cell Tumors
• Neoplasms, Germ Cell and Embryonal
• Recurrence

Intervention

Drug:
• Paclitaxel
200mg/m2 for 3 hours at Cycle 1 day 1 and Cycle 2 day 1 with 14 days between cycles
• 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
• 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
• 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

Locations

Country	Name	City	State
France	Centre Paul Papin	Angers
France	Hopital St André	Bordeaux
France	Institut Bergonié	Bordeaux
France	CHU	Clermont Ferrand
France	Centre Léon Bérard	Lyon
France	Institut Paoli Calmette	Marseille
France	Institut Val d'aurelle	Montpellier
France	Centre Antoine Lacassagne	Nice
France	Hopital TENON	Paris
France	CHU	Strasbourg
France	Institut Claudius Regaud	Toulouse
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Institut Claudius Regaud

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response rate(by chemotherapy or chemotherapy + surgery), pathological complete response rate.		6 months
Secondary	Progression free survival		8 years
Secondary	Time to progression		8 years
Secondary	Toxicity		6 months
Secondary	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
Secondary	Etoposide pharmacokinetics (in particular inter-individual variability of Etoposide plasmatic concentrations AUC in such patients		4 years
Secondary	Genetic polymorphisms involved in response and safety treatments		4 years