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

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ClinicalTrials.gov Identifier: NCT00231582
Recruitment Status : Completed
First Posted : October 4, 2005
Last Update Posted : February 25, 2011
Information provided by:

Study Description
Brief 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.

Condition or disease Intervention/treatment Phase
Testicular Neoplasms Drug: epirubicin Procedure: high-dose and autologous stem cell transplantation Drug: paclitaxel Drug: etoposide Drug: ifosfamide Drug: carboplatin Phase 2

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Detailed Description:

The treatment is designed for relapsed poor prognosis patients with testicular or extra-gonadal GCTs previously treated with cisplatin-containing regimens.

Poor prognosis patients are defined as either relapsed/refractory patients more than one month after cisplatin administration, whether in the course of first-line CT or in that of salvage treatment, or patients who showed evidence of progression after at least 2 lines of cisplatin-containing CT (i.e., BEP and VeIP).

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, and 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.

Non-inclusion criteria are: patients with 'BEYER' score > 3, growing teratoma syndrome, possibility of being treated with a conventional cisplatin-based CT, and previous HD-CT regimen.

During the initial evaluation: each patient must have a clinical evaluation that includes measurements of tumor marker levels, and an imaging work up. The tumor marker levels are determined every week during all the sequence of treatment (normal level < 10 ng/ml for alpha-foetoprotein and < 2 mU/mL for HCG). The tumor mass is measured after the first two cycles of induction/mobilization therapy and at the end of the treatment.

Chemotherapy, patients are scheduled to receive 2 courses of front-line mobilization CT followed by 3 HD-CT supported by PBSCT. The front-line treatment consists in a combination of epirubicin, (100 mg/m² in a 30-minute infusion), and paclitaxel (Taxol, 250 mg/m² given in a 3-hour infusion), administered both on days 1 and 14. These 2 cycles are supported by filgrastim (Neupogen), 5 µg/kg, twice a day from days 2 and 15, respectively, until apheresis performed on days 10-13 and 24-27. Apheresis is stopped when at least 9 x 106 CD34+ cells/Kg of BW are obtained for the 3 grafts. A third cycle is permitted if the number of CD34+ cells is not achieved after the first 2 cycles, provided the patient was responsive to CT, or for any reason decided upon by the investigator.

The first HD-CT regimen consists in an association of thiotepa, 720 mg/m² and taxol, 360 mg/m², both administered in a continuous infusion over 3 days (D34 to D36). The first pack of CD34+ cells is infused on day 39. The second and the third courses (ICE) scheduled on days 62-66 and 90-94 respectively, consist in a combination of etoposide (150 mg/m² twice a day, in a 2-hour infusion, for 5 days), ifosfamide (2 400 mg/m²/d in a 3-hour infusion, for 5 days) supported by sodium mercaptoethanesulfonate (mesna, in a 30-minute infusion every 3 hours, during a 12-hour period, initiated at the same time as the ifosfamide infusion), and carboplatin (AUC 4/d, in a 6-hour infusion, for 5 days). Infusion of PBSCs is planned on days 71 and 99. During the 3 high-dose therapies, G-CSF is administered at a daily dose of 5µg/kg, from the day of PBSC infusion until PMN recovery (i.e., PMN > 1.5 x 109/L). Each of these ICE regimens is delayed if the PMN level is less than 1.5 x 109/L and/or the platelet level less than 100 x 109/L.

Toxicity and response to therapy are evaluated according to the ECOG and WHO criteria. The duration of response is calculated from the date of documented response to the date of progression. The duration of PFS and OS are calculated from the date of inclusion to the date of progression, or death if no progression (PFS), and the date of death (OS), according to Kaplan-Meier's method. Survival curves are established according to the classification proposed by BEYER et al. Progression, death from treatment and withdrawal from protocol for whatever reason are considered as treatment failures. Whenever possible, patients in clinical partial response (PR) with normal tumor markers (PRm-) will be proposed for surgery of residual masses at the end of the whole procedure. Sequential procedures are proposed in the case of multiple metastatic sites. If surgery is complete and the pathological examination does not show any viable tumor, patients will be considered as complete responders. If surgery is complete and the pathological examination showed persistent viable tumor, they will be considered as surgical complete response.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Sequential High-Dose Chemotherapy Combining Two Mobilization and Cyto-Reductive Treatments Followed by Three High-Dose Chemotherapy Regimens Supported by Autologous Stem Cell Transplantation
Study Start Date : September 2004
Primary Completion Date : January 2010
Study Completion Date : January 2010

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: 1
Drug: epirubicin
Procedure: high-dose and autologous stem cell transplantation
high-dose and autologous stem cell transplantation
Drug: paclitaxel
Drug: etoposide
Drug: ifosfamide
Drug: carboplatin

Outcome Measures

Primary Outcome Measures :
  1. Complete response rate [ Time Frame: during de study ]
    Complete response rate

Secondary Outcome Measures :
  1. Survival (overall and progression-free), toxicity, toxic-death rate. [ Time Frame: during the study ]
    Survival (overall and progression-free), toxicity, toxic-death rate.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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
Contacts and Locations

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 ClinicalTrials.gov identifier (NCT number): NCT00231582

Hôpital TENON, Service d'Oncologie Médicale
Paris, France, 75020
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Ministry of Health, France
Baxter Healthcare Corporation
Principal Investigator: Jean-Pierre LOTZ, Pr,MD,PhD Assistance Publique - Hôpitaux de Paris
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Isabelle Brindel, Department of Clinical Research of developpement
ClinicalTrials.gov Identifier: NCT00231582     History of Changes
Other Study ID Numbers: P031101
First Posted: October 4, 2005    Key Record Dates
Last Update Posted: February 25, 2011
Last Verified: March 2007

Keywords provided by Assistance Publique - Hôpitaux de Paris:
High-dose with autologous germ-cell tumors

Additional relevant MeSH terms:
Testicular Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Endocrine System Diseases
Testicular Diseases
Gonadal Disorders
Etoposide phosphate
Isophosphamide mustard
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antibiotics, Antineoplastic
Antineoplastic Agents, Alkylating
Alkylating Agents