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

Study Overview
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Brief Summary
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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 the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with bone marrow transplantation or peripheral stem cell transplantation works in treating patients with relapsed germ cell cancer.

Detailed Description
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OBJECTIVES: Estimate the antitumor activity of 2 courses of paclitaxel and carboplatin regimens with autologous stem cell rescue in patients with relapsed germ cell cancer. Evaluate the toxic effects of paclitaxel, carboplatin and etoposide (VP-16) with stem cell support followed by paclitaxel, carboplatin and ifosfamide with stem cell support in these patients. OUTLINE: Patients receive filgrastim (G-CSF) SC or IV 4 days prior to peripheral blood stem cells (PBSC) apheresis. Autologous bone marrow harvest is performed when adequate stem cells cannot be collected. Patients then receive course 1 of high-dose chemotherapy beginning on day -7 with paclitaxel IV over 24 hours. On days -6 to -4, patients receive etoposide IV over 2 hours and carboplatin (CBDCA) IV over 30 minutes 3 times daily. Following a 2 or 3 week recovery, a second course of chemotherapy begins on day -7, consisting of paclitaxel IV over 24 hours, then CBDCA and ifosfamide on days -6 to -4. Reinfusion of PBSC and marrow begins on day -2 in both course 1 and 2. In addition, G-CSF IV is given twice a day until 3 consecutive postnadir days of granulocytes of at least 1000/mm^3 are maintained. On day 0, stem cells with or without bone marrow product are again administered. Surgery may be performed after course 2 if indicated. PROJECTED ACCRUAL: The expected accrual rate is 12 patients per year over 2 years.

Official Title
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Tandem High-Dose Chemotherapy With Autologous Stem Cell Rescue for Poor-Prognosis Germ Cell Cancer

Conditions
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Brain and Central Nervous System Tumors, Extragonadal Germ Cell Tumor, Ovarian Cancer, Teratoma, Testicular Germ Cell Tumor

Intervention / Treatment
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* Biological: filgrastim
* Drug: carboplatin
* Drug: etoposide
* Drug: ifosfamide
* Drug: paclitaxel
* Procedure: autologous bone marrow transplantation
* Procedure: bone marrow ablation with stem cell support


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Evaluable germ cell cancer (measurable by radiographic study and/or serum tumor marker elevation) and not curable by standard salvage therapy OR viable cancer on resection of post-chemotherapy residual masses in either intermediate or high risk category Bidimensionally measurable disease with measurements performed within 21 days of study entry Tumor marker (alpha-fetoprotein, lactate dehydrogenase, beta-human chorionic gonadotropin) studies performed within 7 days prior to study entry PATIENT CHARACTERISTICS: Age: 16 and over Performance status: Karnofsky 70-100% Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 120,000/mm^3 Hemoglobin at least 10 g/dL Hepatic: Bilirubin no greater than 1.6 mg/dL SGOT and SGPT no greater than 2 times upper limit of normal (ULN) No active hepatitis or cirrhosis Renal: Creatinine clearance at least 70 mL/min Cardiovascular: Ejection fraction (MUGA or echocardiogram) normal No EKG evidence of active cardiac disease (arrhythmias, ischemia) which would contraindicate etoposide and paclitaxel study treatment Pulmonary: PaO_2 at least 70 mm Hg FEV_1 at least 2 L or 75% No history of bleomycin associated or serious lung disease Neurologic: No steroid or glucocorticoid treatment for patients with CNS metastatic disease; at least 1 month with stable post-radiotherapy neurological status and seizure free; if prior seizures, at least 1 month with therapeutic anticonvulsant levels prior to study Prior peripheral neuropathy requires consultation with principal investigator Other: No significant active medical illness precluding study or survival Not HIV positive No prior malignancy within past 5 years except for adequately treated basal cell or squamous cell skin cancer No prior hematologic malignancies PRIOR CONCURRENT THERAPY: Biologic therapy: No prior bone marrow or stem cell rescue with high-dose chemotherapy Chemotherapy: Prior chemotherapy allowed, excluding high-dose therapy with bone marrow or stem cell rescue No prior paclitaxel Endocrine therapy: Not specified Radiotherapy: No concurrent radiotherapy during study Surgery: Recovered from prior surgery

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HD Chemo and Auto Stem Cells<br> | Biological: filgrastim<br>* 5 ug/kg bid beginning 4 days prior to and continuing through stem cell collection.<br>Drug: carboplatin<br>* AUC=7, daily X 3<br>Drug: etoposide<br>* 20 mg/kg by 2 hours infusion daily X 3<br>Drug: ifosfamide<br>* 3 gm/m2 IV over 30 minutes X 3 days<br>Drug: paclitaxel<br>* 425 mg/m2 as 24 hour continuous infusion<br>Procedure: autologous bone marrow transplantation<br>* Given in two divided infusions on day -2 and day 0<br>Procedure: bone marrow ablation with stem cell support<br>* Two cycles of high dose chemotherapy followed by stem cell reinfusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Estimated using the product-limit method of Kaplan and Meier. Progression is defined as an increase o any radiologically measureable tumor by greater than 25% or a greater than 10% increase of elevated tumor markers. | Until disease progression, up to 5 years. | 
| Toxic Effects | Number of Participants with Grade 3 and 4 Adverse Events Related to Protocol-based Therapy | From date of randomization until death of any cause, assessed up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Estimated using the product-limit method of Kaplan and Meier. | Until death from any cause, up to 5 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent malignant testicular germ cell tumor, testicular seminoma, testicular embryonal carcinoma, testicular choriocarcinoma, testicular yolk sac tumor, testicular embryonal carcinoma and teratoma, testicular embryonal carcinoma and teratoma with seminoma, testicular embryonal carcinoma and yolk sac tumor, testicular embryonal carcinoma and yolk sac tumor with seminoma, testicular embryonal carcinoma and seminoma, testicular yolk sac tumor and teratoma, testicular yolk sac tumor and teratoma with seminoma, testicular choriocarcinoma and yolk sac tumor, testicular choriocarcinoma and embryonal carcinoma, testicular choriocarcinoma and teratoma, testicular choriocarcinoma and seminoma, recurrent ovarian germ cell tumor, recurrent extragonadal non-seminomatous germ cell tumor, recurrent extragonadal seminoma, recurrent extragonadal germ cell tumor, adult teratoma, testicular immature teratoma, testicular mature teratoma, ovarian immature teratoma, ovarian mature teratoma, ovarian monodermal and highly specialized teratoma, stage III malignant testicular germ cell tumor, stage IV ovarian germ cell tumor, stage IV extragonadal non-seminomatous germ cell tumor, stage IV extragonadal seminoma, adult central nervous system germ cell tumor