Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients with Relapsed or Refractory Germ Cell Tumors

Summary

Objectives

PRIMARY OBJECTIVE:
I. To compare the overall survival in patients treated with conventional-dose chemotherapy using the paclitaxel, ifosfamide, and cisplatin (TIP) regimen with high-dose chemotherapy (HDCT) plus autologous stem cell transplant (ASCT) using the high-dose carboplatin and etoposide (TI-CE) regimen as initial salvage treatment of patients with relapsed or refractory germ cell tumors (GCT).

SECONDARY OBJECTIVES:
I. To compare the progression-free survival (PFS) of patients treated with initial salvage HDCT with TI-CE versus (vs.) initial salvage conventional-dose chemotherapy (CDCT) with TIP.
II. To compare the favorable response rate (FRR) of patients treated with initial salvage HDCT with TI-CE vs. initial salvage CDCT with TIP.
III. To compare the toxicity, including treatment-related mortality, associated with high-dose chemotherapy and ASCT using TI-CE compared with conventional-dose chemotherapy using TIP as initial salvage treatment for patients with relapsed or refractory GCT.
IV. To prospectively evaluate the International Prognostic Factors Study Group (IPFSG) scoring system as a predictor of outcome to initial salvage therapy in patients with relapsed or refractory GCT.
V. To evaluate the association between tumor marker decline rates of alpha-fetoprotein (AFP) and human chronic gonadotropin (HCG) with overall survival (OS) and PFS.

CORRELATIVE SCIENCE OBJECTIVES:
I. To compare the quality of life among patients >= 18 years treated with TIP vs. those treated with TI-CE using the European Organization for Research and Treatment of Cancer (EORTC) quality of life instruments (EORTC Quality of Life-Core 30 [QOL-C30] and QLQ-Testicular Cancer 26 [TC26]). (Quality of Life Evaluation)
II. To evaluate the association between specific germline polymorphisms and patient outcome to treatment. (Pharmacogenomic)
III. To evaluate the frequency of aberrations in the RAS, PI3K, and p53 pathways among patients with refractory or relapsed GCT entering the study. (Tumor Biology)
IV. To correlate aberrations in the RAS, PI3K, and p53 pathways with patient outcome overall and within each treatment arm. (Tumor Biology)
V. To characterize the range of other genetic aberrations (mutations and copy number gains and losses among 341 cancer-related genes) within relapsed and refractory GCT samples. (Tumor Biology)
VI. To establish a GCT biospecimen bank for future analysis. (Tumor Biology)

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A (TIP): Patients receive paclitaxel intravenously (IV) over 24 hours on day 1, ifosfamide IV over 30 minutes daily and cisplatin IV over 1-96 hours daily on days 2-5, and pegfilgrastim subcutaneously (SC) on day 6, 7, or 8. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

ARM B (TI-CE): Patients receive paclitaxel IV over 3 hours on day 1, ifosfamide IV over 30 minutes daily on days 1-3, and filgrastim SC daily beginning on day 3 and continuing until adequate CD34+ cell collection or day 15, whichever occurs first. Treatment repeats every 14-21 days for 2 cycles in the absence of unacceptable toxicity. Patients then receive carboplatin IV daily and etoposide IV daily on days 1-3, undergo ASCT on day 5, and receive pegfilgrastim SC beginning on day 5 and continuing until absolute neutrophil count (ANC) recovery. Treatment repeats every 21-28 days for 3 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 9, 12, 15, 18, 24, 36, 48, and 60 months.