Clinical trial NCT00003852: Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Germ Cell Tumors
Official title: Phase II Study of Intensive Chemotherapy With Autologous Peripheral Blood Stem Cell Support in Patients With Cisplatin Resistant Germ Cell Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Childhood Germ Cell Tumor
Extragonadal Germ Cell Tumor
Ovarian Cancer
Testicular Germ Cell Tumor
Keywords: recurrent malignant testicular germ cell tumor
childhood germ cell tumor
recurrent ovarian germ cell tumor
extragonadal germ cell tumor
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2004-01-27
Enrollment: 45
Sex: ALL
Minimum age (years): 15
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Angers
country: France
facility: Centre Paul Papin
city: Besancon
country: France
facility: CHR de Besancon - Hopital Jean Minjoz
city: Bordeaux
country: France
facility: Institut Bergonie
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: Centre de Lute Contre le Cancer,Georges-Francois Leclerc
city: Grenoble
country: France
facility: CHR de Grenoble - La Tronche
city: La Rochelle
country: France
facility: Clinique Saint Michel
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut J. Paoli and I. Calmettes
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Hopital d'Instruction des Armees du Val de Grace
city: Reims
country: France
facility: Institut Jean Godinot
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Cloud
country: France
facility: Centre Rene Huguenin
city: Strasbourg
country: France
facility: Hopitaux Universitaire de Strasbourg
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Centre Leon Berard
name: Pierre Biron, MD
role: STUDY_CHAIR
References: