Odansetron and Dexamethasone Alone vs. Odansetron, Dexamethason and Apreptant to Prevent Nausea

Prevention of Nausea and Vomitting Associated With Stem Cell Transplant: Results of a Prospective, Randomized Trial of Aprepitant Used With Highly Emetogenic Preparative Regimens

The purpose of this study is to compare two different treatment protocols for treating nausea and vomiting in patients who have undergone bone marrow transplant. Patients will be assigned to one of two treatment groups.

The first group will recieve ondansetron (Zofran) tablets combined with a medicine called dexamethasone given IV. Both of these drugs are commercially available.

Patients in the second treatment consists of the first two drugs, plus a newly approved drug known as aprepitant (MK-869, Emend). This combination will be the treatment being tested. The combination is approved by the FDA for chemotherapy regimens known to cause a lot of nausea and vomiting. It significantly decreases the delayed (more than 24 hours after therapy) nausea and vomiting seen with these regimens.

Study Overview

• Status: Completed
• Conditions: Nausea; Vomiting
• Intervention / Treatment: Drug: Standard PO (Zofran + Dexamethason); Drug: Aprepitant (MK-869) + Standard PO

Detailed Description

This will be a single center, comparative, randomized, double-blind, phase III trial designed to evaluate the efficacy of the NK-1 antagonist, aprepitant (MK-869), in combination with ondansetron and dexamethasone in the prevention of acute and delayed nausea and vomiting compared to ondansetron and dexamethasone in patients receiving highly emetogenic preparative regimens prior to autologous or allogeneic (related and unrelated) stem cell transplantation.

Patients will be randomized to one of two treatments: dexamethasone 10 mg IV once daily and ondansetron 8 mg orally every 8 hours on each day of the preparative regimen plus one additional day vs. 7.5 mg IV once daily and ondansetron 8 mg orally every 8 hours on each day of the preparative regimen plus one additional day combined with aprepitant, 125 mg orally on the first day of their preparative regimen followed by 80 mg daily on each remaining day of the preparative regimen plus three additional days.

• Study Type: Interventional
• Enrollment (Actual): 181
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of cancer, admitted for myelosupppresive stem cell transplantation. Included preparative regimens include: TBI/VP16/CY, TBI/CY, BU/CY (PO & IV), and BCV
• Age 18 or older
• Alcohol intake <100 gm/d for the last year (< approximately 5 drinks per day)
• Renal function: estimated or measured CrCl 50 ml/min
• Liver function: T.Bili <1.5, AST < 2x ULN, unless due to disease
• Able to swallow tablets and capsules

Exclusion Criteria:

• Age < 18
• High alcohol intake [> 100 gm/d in the last year]
• Allergy or intolerance to: ondansetron or dexamethasone
• Renal dysfunction [measured or estimated CrCl < 50 ml/min]
• Liver dysfunction [T.Bili > 1.5, AST > 2x ULN, unless due to disease]
• Inability to swallow tablets or capsules
• Concurrent condition requiring systemic steroid use
• Nonmyeloablative SCT, patients receiving the conditioning regimens not included [see inclusion criteria]
• History of anticipatory nausea and vomiting

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Standard PO (Zofran + Dexamethasone); Dexamethasone 10 mg (dose blinded) in 50 ml D5W IVPB over 15 minutes daily + ondansetron (Zofran) 8mg PO q 8 hours - repeated qd of the preparative regimen and for 1 day after completion.	Drug: Standard PO (Zofran + Dexamethason); Dexamethasone 10 mg (dose blinded) in 50 ml D5W IVPB over 15 minutes daily + ondansetron 8mg PO q 8 hours - repeated qd of the preparative regimen and for 1 day after completion. A placebo capsule will be given daily on each day of the preparative regimen plus 3 days after. Antiemetic therapy will start a minimum of 30 minutes prior to and continued for 24 hours after completion of the preparative regimen.; Other Names: Ondansetron (Zofran)
Active Comparator: Aprepitant (MK-869) + Standard PO; Dexamethasone 7.5 mg (dose blinded) in 50 ml D5W IVPB over 15 min daily + ondansetron 8mg PO q 8 hours - repeated QD of the preparative regimen and for 1 day after completion. Aprepitant 125mg PO [blinded] will be given a minimum of 30 minutes prior to the preparative regimen on day 1. MK-Aprepitant 80mg PO [blinded] will be given will be given approximately 24 hours later starting on day 2 then each day of the preparative regimen plus 3 days after. Antiemetic therapy will start a minimum of 30 minutes prior to and continued for 24 hours after completion of the preparative regimen.	Drug: Aprepitant (MK-869) + Standard PO; Dexamethasone 7.5 mg (dose blinded) in 50 ml D5W IVPB over 15 min daily + ondansetron 8mg PO q 8 hours - repeated QD of the preparative regimen and for 1 day after completion. Aprepitant 125mg PO [blinded] will be given a minimum of 30 minutes prior to the preparative regimen on day 1. MK-Aprepitant 80mg PO [blinded] will be given will be given approximately 24 hours later starting on day 2 then each day of the preparative regimen plus 3 days after. Antiemetic therapy will start a minimum of 30 minutes prior to and continued for 24 hours after completion of the preparative regimen.; Other Names: Ondansetron + Dexamethason (Standard PO)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rates Among Standard of Care and Combination Therapy Groups.	Comparison of complete response (CR) rates between patients receiving ondansetron and dexamethasone and those receiving ondansetron and dexamethasone plus NK-1 antagonist, aprepitant. CR is defined as no emesis and with normal oral intake. Disease response not applicable.	14 days

Collaborators and Investigators

• Sponsor: Loyola University
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Patrick Stiff, MD, Loyola University Cardinal Bernadin Cancer Center

Study record dates

Study Major Dates

• Study Start: August 1, 2003
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: October 27, 2008
• First Submitted That Met QC Criteria: October 28, 2008
• First Posted (Estimate): October 29, 2008

Study Record Updates

• Last Update Posted (Actual): July 27, 2018
• Last Update Submitted That Met QC Criteria: June 29, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Nausea; Vomiting; Bone Marrow Transplant; NK-1 antagonist
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antipruritics; Neurokinin-1 Receptor Antagonists; Ondansetron; Aprepitant
• Other Study ID Numbers: 106578