Emend and Ondansetron Compared to Ondansetron Alone to Prevent CINV in Glioma Patients Receiving Temozolomide

NCT ID: NCT01450826

Last Updated: 2018-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-24
• Study Completion Date: 2017-04-21

Brief Summary

Patients diagnosed with malignant glioma who are receiving temozolomide will be accrued in this open label, phase 2, randomized single institution trial of aprepitant in combination with ondansetron versus ondansetron alone for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Sixty-eight (68) patients will be randomized to each arm of the study.

Detailed Description

Sixty-eight (68) patients will be randomized to each arm of the study. Patient randomization will be stratified by grade of tumor (1 or 2 versus 3 or 4) and the number of prior progressions (0 or 1 versus 2). Within each of the 4 strata defined by these factors, a permuted block randomization scheme will be used to assign patients to receive either aprepitant in combination with ondansetron or ondansetron alone.

Though the study is comparative, the goal of the study is to determine whether aprepitant is worthy of further investigation in this setting, and not to make definitive statements about the comparative effectiveness of ondansetron treatment with or without aprepitant.

Conditions

Nausea; Vomiting; Glioma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

aprepitant+ondansetron

On day 1, patients will receive a single oral dose of Aprepitant 125 mg p.o, 1 hour before first dose of the 5-day oral temozolomide regimen. This will be followed by Aprepitant 80 mg p.o. on days 2 -5 (1 hour prior to temozolomide). Additionally, On days 1-5, patients receive a single dose of Ondansetron 30 minutes before the receiving their prescribed dose of 5-day oral temozolomide.

Group Type: ACTIVE_COMPARATOR

aprepitant

Intervention Type: DRUG

On day 1, eligible patients will receive a single oral dose of Aprepitant 125 mg p.o, 1 hour before first dose of the 5-day oral temozolomide regimen. This will be followed by Aprepitant 80 mg p.o. on days 2 -5 (1 hour prior to temozolomide).

ondansetron

Intervention Type: DRUG

On Days 1-5, eligible patients will receive a single oral dose of Ondansetron, 30 minutes before first dose of the 5 -day oral temozolomide regimen.

ondansetron

On days 1-5, patients receive a single dose of Ondansetron 30 minutes before the receiving their prescribed dose of 5-day oral temozolomide.

Group Type: ACTIVE_COMPARATOR

ondansetron

Intervention Type: DRUG

On Days 1-5, eligible patients will receive a single oral dose of Ondansetron, 30 minutes before first dose of the 5 -day oral temozolomide regimen.

Interventions

aprepitant

On day 1, eligible patients will receive a single oral dose of Aprepitant 125 mg p.o, 1 hour before first dose of the 5-day oral temozolomide regimen. This will be followed by Aprepitant 80 mg p.o. on days 2 -5 (1 hour prior to temozolomide).

Intervention Type: DRUG

ondansetron

On Days 1-5, eligible patients will receive a single oral dose of Ondansetron, 30 minutes before first dose of the 5 -day oral temozolomide regimen.

Intervention Type: DRUG

Other Intervention Names

Emend; Zofran

Eligibility Criteria

Inclusion Criteria

• Patients must have histologically confirmed diagnosis of glioma (either low or high grade) and be either chemotherapy naïve or non-naïve and scheduled to receive temozolomide-based +/- Bevacizumab- based chemotherapy. Patients with recurrent disease whose diagnostic pathology confirmed glioma (either low or high grade) will not need re-biopsy.
• Age ≥ 18 years
• ≤ 2 prior chemotherapeutic regimens
• Patient is scheduled to receive temozolomide at either 150 mg/m2 or 200mg/m2 by mouth for 5 days out of a 28 day cycle +/- bevacizumab.
• Study participation will occur during the first cycle of the 5 day temozolomide course.
• An interval of at least 6 weeks between prior surgical resection and study enrollment
• Karnofsky ≥ 60%.
• Hematocrit > 29%, absolute neutrophil count (ANC) > 1,000 cells/µl, platelets > 100,000 cells/µl
• Serum creatinine < 1.5 mg/dl, serum glutamic oxaloacetic transaminase (SGOT) and bilirubin < 1.5 times upper limit of normal
• For patients on oral corticosteroids, they must be stable clinically on corticosteroids or tapered off prior to starting the study drug. For patients taking dexamethasone, the dose should not exceed 8 mg qd (or 4 mg twice a day), if clinically stable, and the dose should not be escalated over entry dose level, if clinically possible. The patient's dose of dexamethasone will be evaluated by the PI, the patient's study physician, and/or the study pharmacist on a case by case basis for safety. All doses of oral corticosteroids will be reduced by 50% to avoid drug to drug interactions with Aprepitant, unless oral corticosteroids are at physiologic dose (e.g. dexamethasone 1 mg, prednisone 10 mg, or cortisone 30 mg). It is recommended that oral corticosteroid doses be escalated back to full dose on Day 7 (2 days after Aprepitant is discontinued) based on Aprepitant half-life pharmacokinetic data, and expert clinical opinion.
• Signed informed consent approved by the Institutional Review Board prior to patient entry
• If sexually active, patients will take contraceptive measures for the duration of protocol treatment and continue until one month after treatment. The efficacy of hormonal contraceptives during and for 28 days following the last dose of Aprepitant may be reduced. Alternative or back-up methods of contraception must be used.
• Approved rescue medication for the treatment of nausea and vomiting is permitted at the discretion of the investigator. The rescue antiemetics allowed will include: ondansetron, granisetron and lorazepam.

Exclusion Criteria

• Pregnant or breast-feeding (While both aprepitant and ondansetron are classified as Category B drugs, an eligibility criteria for this study is that the patient be scheduled to receive a temozolomide-based chemotherapy regimen +/- bevacizumab, which are Category D and C drugs respectively. Therefore, while not considered necessary for the administration of the current study drugs, a pregnancy test should be a part of normal clinical care for the patients in this study, if the patient is determined to be of child-bearing potential.)
• No prior nitrosourea (e.g. lomustine, carmustine)
• Inability or unwillingness to understand or cooperate with study procedures
• Concurrent administration of CYP3A4 enzyme-inducing anti-epileptic drugs (EIAEDs) including phenytoin, phenobarbitol, carbamazepine, oxcarbazepine or primidone
• Prohibited medications: Patients taking CYP3A4 enzyme inducers and moderate or strong inhibitors will be excluded from this trial.
• Received any drug with potential anti-emetic effect within 24 hours prior to the start of study-designated chemotherapeutic agent: HT3 receptor or substance P/neurokinin 1(NK1) receptor antagonists; Dopamine receptor antagonists (metoclopramide); Phenothiazine anti-emetics (prochlorperazine, thiethylperazine and perphenazine); Diphenhydramine, scopolamine, chlorpheniramine maleate, trimethobenzamide; Haloperidol, droperidol, tetrahydrocannabinol, or nabilone
• Any vomiting, retching or NCI Common Toxicity Criteria v.4.0 grade 2-4 nausea 24 hours preceding chemotherapy
• Ongoing vomiting from any organic etiology
• Will receive radiotherapy of cranium within one week prior to or during the study

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

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Katy Peters

OTHER

Sponsor Role: lead

Responsible Party

Katy Peters

Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Mary Lou Affronti, DNP, RN, MHSc, ANP

Role: PRINCIPAL_INVESTIGATOR

Duke University

Katherine B Peters, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

The Preston Robert Tisch Brain Tumor Center at Duke

Durham, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://tischbraintumorcenter.duke.edu/

The Preston Robert Tisch Brain Tumor Center

http://www.dukecancerinstitute.org/clinical-trials

Duke Cancer Institute

Other Identifiers

Pro00031206

Identifier Type: -

Identifier Source: org_study_id