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

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Hoosier Cancer Research Network
ClinicalTrials.gov Identifier:
NCT00572572
First received: December 11, 2007
Last updated: March 8, 2016
Last verified: March 2016
  Purpose
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.

Condition Intervention Phase
Germ Cell Tumors
Drug: Aprepitant
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Supportive Care
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Hoosier Cancer Research Network:

Primary Outcome Measures:
  • Complete Response. [ Time Frame: Participants were evaluated from start of treatment through day 8 of cycle 2. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Proportion of Patients With no Emesis During the Acute CINV Time Period (Cycle Days 1-5) [ Time Frame: Participants were evaluated from cycle days 1-5. ] [ Designated as safety issue: No ]
    Proportion of patients with no emesis regardless of use of rescue medication during cycle days 1-5.

  • Proportion of Patients With no Emesis During the Delayed CINV Time Period (Cycle Days 6-8) [ Time Frame: Participants were evaluated from cycle days 6-8. ] [ Designated as safety issue: No ]
    Proportion of patients with no emesis regardless of use of rescue medication during cycle days 6-8.

  • Visual Analouge (VAS) 100mm Scale Score [ Time Frame: Days 1-8 ] [ Designated as safety issue: No ]
    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.

  • MD Anderson Symptom Inventory Score [ Time Frame: Days 1-8 ] [ Designated as safety issue: No ]
    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.

  • Preferred Treatment Cycle [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    Participants were asked which treatment cycles was preferable - aprepitant or placebo cycle.


Enrollment: 69
Study Start Date: December 2007
Study Completion Date: February 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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
  Eligibility

Ages Eligible for Study:   15 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00572572

Locations
United States, Indiana
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Medical Consultants, P.C.
Muncie, Indiana, United States, 47303
United States, Missouri
Siteman Cancer Center
St. Louis, Missouri, United States, 63110
United States, Oregon
Providence Portland Medical Center
Portland, Oregon, United States, 97213
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Wisconsin
Froedtert/Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Hoosier Cancer Research Network
Merck Sharp & Dohme Corp.
Investigators
Study Chair: Lawrence Einhorn, M.D. Hoosier Oncology Group, Inc.
  More Information

Additional Information:
Publications:
Responsible Party: Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT00572572     History of Changes
Other Study ID Numbers: QL05-37 
Study First Received: December 11, 2007
Results First Received: December 17, 2015
Last Updated: March 8, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Dexamethasone acetate
Dexamethasone
Aprepitant
Fosaprepitant
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurokinin-1 Receptor Antagonists
Neurotransmitter Agents

ClinicalTrials.gov processed this record on August 25, 2016