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

City of Hope Medical Center48 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Interventions

filgrastimBIOLOGICAL

5 ug/kg bid beginning 4 days prior to and continuing through stem cell collection.

carboplatinDRUG

AUC=7, daily X 3

etoposideDRUG

20 mg/kg by 2 hours infusion daily X 3

ifosfamideDRUG

3 gm/m2 IV over 30 minutes X 3 days

paclitaxelDRUG

425 mg/m2 as 24 hour continuous infusion

autologous bone marrow transplantationPROCEDURE

Given in two divided infusions on day -2 and day 0

bone marrow ablation with stem cell supportPROCEDURE

Two cycles of high dose chemotherapy followed by stem cell reinfusion

Eligibility

Sex: ALLMin age: 16 YearsMax age: 120 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: Until disease progression, up to 5 years.

Toxic Effects

Number of Participants with Grade 3 and 4 Adverse Events Related to Protocol-based Therapy

Time frame: From date of randomization until death of any cause, assessed up to 12 weeks

Secondary Outcomes

Overall Survival

Estimated using the product-limit method of Kaplan and Meier.

Time frame: Until death from any cause, up to 5 years.