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.

Condition	Treatment or Intervention	Phase
recurrent testicular cancer recurrent ovarian germ cell tumor pediatric germ cell tumor extragonadal germ cell tumor	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: colony-stimulating factor therapy  Procedure: peripheral blood stem cell transplantation  Procedure: cytokine therapy  Drug: bone marrow ablation with stem cell support  Drug: carboplatin  Drug: cyclophosphamide  Drug: epirubicin  Drug: etoposide  Drug: filgrastim  Drug: ifosfamide  Drug: paclitaxel  Drug: thiotepa	Phase II

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  15 Years and above

Criteria

PROTOCOL ENTRY 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

--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

--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

France
      Centre Antoine Lacassagne, Nice,  06189,  France
      Centre de Lute Contre le Cancer,Georges-Francois Leclerc, Dijon,  21079,  France
      Centre Henri Becquerel, Rouen,  76038,  France
      Centre Jean Perrin, Clermont-Ferrand,  63011,  France
      Centre Leon Berard, Lyon,  69373,  France
      Centre Paul Papin, Angers,  49036,  France
      Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle, Montpellier,  34298,  France
      Centre Regional Francois Baclesse, Caen,  14076,  France
      Centre Rene Huguenin, Saint Cloud,  92211,  France
      CHR de Besancon - Hopital Jean Minjoz, Besancon,  25030,  France
      CHR de Grenoble - La Tronche, Grenoble,  38043,  France
      Clinique Saint Michel, La Rochelle,  17000,  France
      Hopital d'Instruction des Armees du Val de Grace, Paris,  France
      Hopitaux Universitaire de Strasbourg, Strasbourg,  67091,  France
      Institut Bergonie, Bordeaux,  33076,  France
      Institut Gustave Roussy, Villejuif,  F-94805,  France
      Institut J. Paoli and I. Calmettes, Marseille,  13273,  France
      Institut Jean Godinot, Reims,  51056,  France

Study chairs or principal investigators

Pierre Biron,  Study Chair,  Federation Nationale des Centres de Lutte Contre le Cancer   

Study ID Numbers:  CDR0000067015; FRE-FNCLCC-GETUG-04; EU-99004
Record last reviewed:  January 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003852
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08