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

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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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

Conditions
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Germ Cell Tumors

Intervention / Treatment
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* Drug: Aprepitant
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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Male

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: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Aprepitant, Then Placebo<br>Participants first received Aprepitant 125mg PO day 3 then 80mg on days 4 and 7 during study cycle 1, then received matched placebo PO daily on days 3 through 7 during study cycle 2 | Drug: Aprepitant<br>* Subjects will be randomized to receive aprepitant 125mg PO day 3 then 80mg on days 4-7 on either cycle 1 or cycle 2.<br>Drug: Placebo<br>* Subjects will be randomized to receive placebo on days 3-7 on either cycle 1 or cycle 2.<br>|
| Experimental: Arm B: Placebo, Then Aprepitant<br>Participants first received matched placebo PO daily on days 3 through 7 during study cycle 1, then received Aprepitant 125mg PO day 3 then 80mg on days 4 and 7 during study cycle 2 | Drug: Aprepitant<br>* Subjects will be randomized to receive aprepitant 125mg PO day 3 then 80mg on days 4-7 on either cycle 1 or cycle 2.<br>Drug: Placebo<br>* Subjects will be randomized to receive placebo on days 3-7 on either cycle 1 or cycle 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response. | Participants were followed for chemotherapy induced nausea and vomiting (CINV) through day 8 of cycle 2. Complete response is defined as no emetic episodes and no use of rescue medication. | Participants were evaluated from start of treatment through day 8 of cycle 2. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With no Emesis During the Acute CINV Time Period (Cycle Days 1-5) | Proportion of patients with no emesis regardless of use of rescue medication during cycle days 1-5. | Participants were evaluated from cycle days 1-5. | 
| Proportion of Patients With no Emesis During the Delayed CINV Time Period (Cycle Days 6-8) | Proportion of patients with no emesis regardless of use of rescue medication during cycle days 6-8. | Participants were evaluated from cycle days 6-8. | 
| Visual Analouge (VAS) 100mm Scale Score | The Visual Analouge (VAS) 100mm Scale Score for Chemotherapy Induced Nausea and Vomiting (CINV). Participants were asked to mark a linear scale 100mm in length representing their level of nausea with 0mm indicating no nausea and 100mm indicating severe nausea. The mean VAS scores for days 1-8 combined, by treatment (Aprepitant vs. Placebo) were reported. | Days 1-8 | 
| MD Anderson Symptom Inventory Score | The MD Anderson Symptom Inventory (MDASI) is a brief measure of the severity and impact of cancer-related symptoms. Thirteen core items measure the severity of symptoms and six additional items measure the impact of symptoms. All items are rated on a scale from 0 (not present or did not interfere) to 10 (maximal severity or interference). The mean value of the total nineteen items ranges from 0 to 10. | Days 1-8 | 
| Preferred Treatment Cycle | Participants were asked which treatment cycles was preferable - aprepitant or placebo cycle. | 2 months |