Aprepitant + a 5HT3 + Dexamethasone in Patients With Germ Cell Tumors

Phase III, Double-Blind, Placebo-Controlled, Crossover Study Evaluating Aprepitant in Combination With a 5HT3 & Dexamethasone in Patients With Germ Cell Tumors Undergoing 5 Day Cisplatin-Based Chemotherapy Regimen

Aprepitant is currently approved for prophylaxis of acute and delayed CINV for highly emetogenic chemotherapy regimens, including cisplatin; however, it has not yet been studied in multiple-day chemotherapy treatment programs. This study will compare the addition of aprepitant compared to placebo administered on days 3,4,5 of chemotherapy administration for acute CINV prophylaxis with standard antiemetic prophylaxis and days 6 and 7 for delayed CINV prophylaxis in a double-blind, randomized, crossover study design.

OUTLINE: This is a multi-center trial.

Subjects will be stratified prior to randomization based on previous administration of chemotherapy.

Subjects will randomize to aprepitant or placebo with their first study cycle of chemotherapy and then cross over to opposite treatment with the second study cycle.

Cisplatin-based regimen for germ cell tumors containing 20mg/m2/day IV days 1 through 5, first day of chemotherapy administration is day 1. Permitted treatment regimens:

Regimen 1 (BEP) Cisplatin (20mg/m2/day) IV on days 1 to 5 Etoposide (100 mg/m2/day) IV on days 1 to 5 Bleomycin 30 U/IV on days 1, 8, 15

Regimen 2 (EP) Cisplatin (20mg/m2/day) IV on days 1 to 5 Etoposide (100 mg/m2/day) IV on days 1 to 5

Regimen 3 (VIP) Cisplatin (20mg/m2/day) IV on days 1 to 5 Ifosfamide (1200 mg/m2/day) IV on days 1 to 5 (with mesna uroprophylaxis at 100% ifosfamide dosing) Etoposide (75 mg/m2/day) IV on days 1 to 5

Regimen 4 (VeIP) Cisplatin (20mg/m2/day) IV on days 1 to 5 Ifosfamide (1200 mg/m2/day) IV on days 1 to 5 (with mesna uroprophylaxis at 100% ifosfamide dosing) Vinblastine (0.11 mg/kg/day) IV on days 1 and 2

Regimen 5 (EC) Cisplatin (20mg/m2/day) IV on days 1 to 5 Epirubicin (90 mg/m2/day) IV on day 1

Patients are treated on study for two cycles. At the completion of protocol therapy patients will receive additional chemotherapy at the discretion of the treating investigator.

If a patient requires discontinuation of one medication or more on a regimen, the patient must be discontinued from the study.

Performance Status:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin < 3 x upper limit of normal
• Aspartate aminotransferase (AST, SGOT) < 3 x upper limit of normal
• Alanine aminotransferase (ALT, SGPT) < 3 x upper limit of normal
• Alk Phos < 3 x upper limit of normal

Renal:

• Serum Creatinine <2 mg/dL

Pulmonary:

• Not specified

Inclusion Criteria:

• Histologic, serologic or clinical evidence of germ cell tumor.
• Patients scheduled to receive a 5 day fractionated cisplatin-based combination chemotherapy on permitted regimens
• Prior chemotherapy is allowed. Patients will be stratified based on previous treatment.
• Male patients 15 years of age or older at time of registration.
• Patient will provide written informed consent and authorization to release personal health information.

Exclusion Criteria:

• No known history of anticipatory nausea or vomiting.
• No use of another antiemetic agent within 72 hours prior to beginning chemotherapy.
• No known central nervous system (CNS) metastasis.
• No known hypersensitivity to any component of study regimen.
• No concurrent participation in a clinical trial which involves another investigational agent.
• No use of warfarin while on study.
• No use of agents expected to induce the metabolism of aprepitant which include: Rifampin, Rifabutin, Phenytoin, Carbamazepine, and barbiturates.
• No use of agents which may impair metabolism of aprepitant which include: Cisapride, macrolide antibiotics (Erythromycin, Clarithromycin, Azithromycin), azole antifungal agents (Ketoconazole, Itraconazole, Voriconazole, Fluconazole), Amifostine, Nelfinavir and Ritonavir.