Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Germ Cell Tumors

NCT ID: NCT00003852

Last Updated: 2016-06-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-03-31
• Study Completion Date: 2000-03-31

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow patients to tolerate higher doses of chemotherapy and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and peripheral stem cell transplantation in treating patients who have germ cell tumors that have not responded to previous chemotherapy.

Detailed Description

OBJECTIVES: I. Determine the complete response rate (chemotherapy complete response, pathological complete response, or surgical complete response) to intensive chemotherapy with autologous peripheral blood stem cell support in patients with cisplatin resistant germ cell tumors. II. Determine duration of complete response and survival of these patients after this therapy. III. Determine the toxic effects of this regimen in these patients. IV. Determine the pharmacokinetics of this regimen and the relationship between these pharmacokinetics, nature and duration of response to treatment, and the toxic effects in these patients.

OUTLINE: This is an open label, multicenter study. Patients receive epirubicin IV over 15 minutes and paclitaxel IV over 3 hours on day 1, then filgrastim (G-CSF) subcutaneously (SQ) on days 5-14. Peripheral blood stem cells (PBSC) are collected on days 13 and 14. This course is repeated beginning on day 15. Patients then undergo a three part intensification regimen. Part I: Patients receive cyclophosphamide IV and thiotepa IV by continuous infusion on days 34 and 35. PBSC are reinfused on day 38, and G-CSF SQ is administered from day 39 until blood cell counts recover. Part II: Patients receive etoposide IV over 2 hours, ifosfamide IV over 4 hours, and carboplatin IV over 6 hours on days 62-66. PBSC are reinfused on day 70, and eventually G-CSF begins on day 71. Part III: Patients receive etoposide, ifosfamide, and carboplatin on days 90-94 as in part II. PBSC are reinfused on day 98 and eventually G-CSF begins on day 99. Patients are followed every month for the first year, every 2 months for the second year, every 6 months for the third and fourth years, then annually thereafter.

PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study within 2 years.

Conditions

Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Ovarian Cancer; Testicular Germ Cell Tumor

Study Design

• Primary Study Purpose: TREATMENT

Interventions

filgrastim

Intervention Type: BIOLOGICAL

carboplatin

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

epirubicin hydrochloride

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

ifosfamide

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

thiotepa

Intervention Type: DRUG

bone marrow ablation with stem cell support

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically or cytologically proven germ cell tumor Seminoma or nondysgerminoma origin Gonadal (testicular or ovarian) OR Extragonadal OR Retroperitoneal OR Primitive mediastinal AFP elevated and/or HCG greater than 200 mIU/mL No growing teratoma Refractory disease to any treatment line Refractory disease is defined by the elevation of AFP and/or HCG during the chemotherapy Refractory to treatment line consisting of one conventional dose of cisplatin (dose intensity greater than 33 mg/m2/week) OR at least 1 month since last course of chemotherapy with or without increase in the size of measurable lesions OR Received 2 regimens of conventional chemotherapy, typically the following: Bleomycin, etoposide, and cisplatin: 3-4 courses* OR Etoposide and cisplatin: 4 courses* AND Vinblastine, etoposide, ifosfamide, cisplatin: 4 courses of 3 week regimen (as standard salvage chemotherapy)* * Unless patients could be treated with a first line conventional treatment OR a first salvage conventional treatment especially patients who could be treated with T93 good prognosis protocol or T93 bad prognosis protocol or IT94 protocol Bidimensionally measurable disease OR Significant elevation of tumor markers: HCG, free beta-HCG, AFP OR Evaluable disease plus increase in tumor markers No germ cell CNS tumors or clinically significant CNS metastases

PATIENT CHARACTERISTICS: Age: Over 15 Performance status: ECOG 0-2 Life expectancy: Greater than 3 months Hematopoietic: WBC greater than 3,000/mm3 AND Platelet count greater than 150,000/mm3 Hepatic: Bilirubin less than 1.5 times normal SGOT/SGPT less than 2 times upper limit of normal (ULN) Alkaline phosphatase less than 2 times ULN Gamma glutamyl transferase less than 2 times ULN Renal: Creatinine less than 1.4 mg/dL Creatine clearance greater than 60 mL/min Cardiovascular: No cardiac insufficiency LVEF at least 50% Other: HIV negative No other malignancy except basal cell skin cancer

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics No prior intensive chemotherapy with stem cell support Endocrine therapy: Not specified Radiotherapy: Prior prophylactic anterior irradiation of the diaphragm for stage I seminoma allowed Surgery: Not specified

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UNICANCER

OTHER

Sponsor Role: lead

Principal Investigators

Pierre Biron, MD

Role: STUDY_CHAIR

Centre Leon Berard

Locations

Centre Paul Papin

Angers, , France

CHR de Besancon - Hopital Jean Minjoz

Besançon, , France

Institut Bergonie

Bordeaux, , France

Centre Regional Francois Baclesse

Caen, , France

Centre Jean Perrin

Clermont-Ferrand, , France

Centre de Lute Contre le Cancer,Georges-Francois Leclerc

Dijon, , France

CHR de Grenoble - La Tronche

Grenoble, , France

Clinique Saint Michel

La Rochelle, , France

Centre Leon Berard

Lyon, , France

Institut J. Paoli and I. Calmettes

Marseille, , France

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

Montpellier, , France

Centre Antoine Lacassagne

Nice, , France

Hopital d'Instruction des Armees du Val de Grace

Paris, , France

Institut Jean Godinot

Reims, , France

Centre Henri Becquerel

Rouen, , France

Centre Rene Huguenin

Saint-Cloud, , France

Hopitaux Universitaire de Strasbourg

Strasbourg, , France

Institut Gustave Roussy

Villejuif, , France

Countries

France

Other Identifiers

FRE-FNCLCC-GETUG-04

Identifier Type: -

Identifier Source: secondary_id

EU-99004

Identifier Type: -

Identifier Source: secondary_id

CDR0000067015

Identifier Type: -

Identifier Source: org_study_id