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

NCT ID: NCT00781768

Last Updated: 2018-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 181 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-08-31
• Study Completion Date: 2010-07-31

Brief Summary

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.

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.

Conditions

Nausea; Vomiting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Standard PO (Zofran + Dexamethason)

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

Aprepitant (MK-869) + Standard PO

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Ondansetron (Zofran); Ondansetron + Dexamethason (Standard PO)

Eligibility Criteria

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

• History of anticipatory nausea and vomiting

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Loyola University

OTHER

Sponsor Role: lead

Responsible Party

Patrick Stiff

Professor and Director of the Cardinal Bernardin Cancer Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Patrick Stiff, MD

Role: PRINCIPAL_INVESTIGATOR

Loyola University Cardinal Bernadin Cancer Center

Other Identifiers

106578

Identifier Type: -

Identifier Source: org_study_id