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.

Study Overview

• Status: Completed
• Conditions: Germ Cell Tumors
• Intervention / Treatment: Drug: Aprepitant; Drug: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Simon Cancer Center
    • Muncie, Indiana, United States, 47303
      • Medical Consultants, P.C.
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Siteman Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert/Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Aprepitant, Then Placebo; 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; Subjects will be randomized to receive aprepitant 125mg PO day 3 then 80mg on days 4-7 on either cycle 1 or cycle 2.; Drug: Placebo; Subjects will be randomized to receive placebo on days 3-7 on either cycle 1 or cycle 2.
Experimental: Arm B: Placebo, Then Aprepitant; 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; Subjects will be randomized to receive aprepitant 125mg PO day 3 then 80mg on days 4-7 on either cycle 1 or cycle 2.; Drug: Placebo; Subjects will be randomized to receive placebo on days 3-7 on either cycle 1 or cycle 2.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hoosier Cancer Research Network
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Chair: Lawrence Einhorn, M.D., Hoosier Oncology Group, Inc.

Publications and helpful links

General Publications

• Albany C, Brames MJ, Fausel C, Johnson CS, Picus J, Einhorn LH. Randomized, double-blind, placebo-controlled, phase III cross-over study evaluating the oral neurokinin-1 antagonist aprepitant in combination with a 5HT3 receptor antagonist and dexamethasone in patients with germ cell tumors receiving 5-day cisplatin combination chemotherapy regimens: a hoosier oncology group study. J Clin Oncol. 2012 Nov 10;30(32):3998-4003. doi: 10.1200/JCO.2011.39.5558. Epub 2012 Aug 20.

Helpful Links

• Hoosier Oncology Group Home Page

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: December 11, 2007
• First Submitted That Met QC Criteria: December 12, 2007
• First Posted (Estimate): December 13, 2007

Study Record Updates

• Last Update Posted (Estimate): April 6, 2016
• Last Update Submitted That Met QC Criteria: March 8, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Germ Cell and Embryonal; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Neurokinin-1 Receptor Antagonists; Aprepitant
• Other Study ID Numbers: QL05-37