High-dose Chemotherapy With Autologous Stem Cell Transplantation in Poor Prognosis Germ-cell Tumors: TAXIF II

• Status: Completed
• Trial end date: 2010-01-01
• Target enrollment: 0
• Participant gender: Male

Summary

High-dose chemotherapy (HD-CT) is able to circumvent platinum-resistance of resistant/refractory germ-cell tumors (GCTs), but expectancy of cure remains low. New strategies are needed with new drugs and a sequential approach.

Patients with relapsed (but not absolutely refractory to Cisplatinum-based chemotherapy) poor-prognosis GCTs are scheduled to receive 2 cycles combining epirubicin and paclitaxel followed by 3 consecutive HD-CT supported by stem cell transplantation. One course will combine Taxol, 360 mg/m² + thiotepa, 720 mg/m², followed by two ICE regimens (Ifosfamide, 12 g/m², carboplatin, AUC 20, etoposide, 1500 mg/m²).

This phase II study is designed as a Gehan method. The main objective of the study is the complete response rate. With this aim in view, it is planned to enroll in its first step 14 patients to insure that if no complete response (CR) is noticed, study would be stopped for inefficacy (i.e., a CR rate lower than 20%). If one or more CR are noticed, protocol specified that up to 45 patients will be included in order to reduce the confidence interval (CI) of the CR rate. Secondary objectives are the overall response rate (RR), the overall survival (OS) and the progression-free survival (PFS) rates, toxicity and toxic death rate. The statistical analysis is done in terms of intent-to-treat.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Amgen; Baxter Healthcare Corporation; Ministry of Health, France
• Treatments: Carboplatin; Epirubicin; Etoposide; Etoposide phosphate; Ifosfamide; Isophosphamide mustard; Paclitaxel

Criteria

Inclusion Criteria:

Eligibility requirements includes the following criteria:

• Age >18 years and < 65

• Performance status < 3

• Histologically or biologically documented GCTs

• Testicular, abdominal, or mediastinal tumors

• Measurable or evaluable disease

• Life expectancy > 3 months

• Normal cardiac, liver, and renal function tests

• Absence of infection

• HIV negative test

• Signed informed consent

• All patients had to have been previously treated with at least one line of a cisplatin-containing regimen and were included if they were refractory after one or two line(s) of cisplatin-based CT, or had relapsed after two lines of a cisplatin-based CT

Exclusion Criteria:

• Fireproof diseases (progress unless month with regard to the last cycle of chemotherapy or in the course of chemotherapy)

• Relapses after complete answer obtained by surgery ( sCR )

• Neuropathy of superior rank or = II - renal Function (Office) superior creatinine or = 125 mmol/l and/or clearance of the creatinine subordinate or = II 60ml / mn

• Antecedents of congestive even compensated cardiac insufficiency

• Hurts of growing teratoma that is measurable hurts increasing by size (cutting) in the absence of rise of marker pens

• Extensive chemotherapy with support of haematopoietic stem cells. NB: A previous preventive irradiation under diaphragmatitis for a seminoma stage I (dose from 24 to 30 Gy in classic spreading) does not establish one against formal indication. However, an estimation clarifies capacities of the haematopoietic marrow is recommended with observation of the evolution of the NFP in the course of chemotherapy and quantification of cells CD 34 + in the peripheral blood. It's the same of the case where a chemotherapy by carboplatine was realized