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

NCT01450826 | Completed Phase 2 Results

• 1 other identifier: Pro00031206
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

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.

Conditions

Nausea; Vomiting; Glioma

Keywords

Chemotherapy induced nausea and vomiting; CINV; Glioma; Temozolomide; Temodar; Aprepitant; Emend; Ondansetron; Zofran; Pro00031206; Affronti; Peters; Duke; Preston Robert Tisch Brain Tumor Center

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients Achieving Complete Control (CC)

  Complete control (CC): study days 1-7 (acute and delayed CINV) the proportion of patients achieving complete control (CC); defined as no emetic episode, no need for rescue medication during days 1-7; number of emetic episodes daily; time to first emetic episode; as captured by the MAT (MASCC Antiemesis Tool)/Osoba survey (MASCC refers to Multinational Association for Supportive Care in Cancer™). Severity of nausea and other toxicities measured daily by the NCI Common Toxicity Criteria (version 4.0).

  7 days

Secondary Outcomes (3)

• Proportion of Patients Achieving an Acute and Delayed Complete Response (CR)

  7 days

• Patient's Global Satisfaction With the Antiemetic Regimen

  7 days

• Time to Treatment Failure

  7 days

Study Arms (2)

aprepitant+ondansetron

ACTIVE COMPARATOR

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.

Drug: aprepitant; Drug: ondansetron

ondansetron

ACTIVE COMPARATOR

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

Drug: ondansetron

Interventions

aprepitant 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).

Also known as: Emend

aprepitant+ondansetron

ondansetron 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.

Also known as: Zofran

aprepitant+ondansetron; ondansetron

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Katy Peters: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

The Preston Robert Tisch Brain Tumor Center at Duke

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center
• Duke Cancer Institute

MeSH Terms

Conditions

Nausea; Vomiting; Glioma

Interventions

Aprepitant; Ondansetron

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Imidazoles; Azoles; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Mary Lou Affronti, DNP, RN, MHSc, ANP
• Organization: Duke University Medical Center

mary.affronti@duke.edu

9196845301

Study Officials

• Mary Lou Affronti, DNP, RN, MHSc, ANP

  Duke University

  PRINCIPAL INVESTIGATOR

• Katherine B Peters, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 10, 2011
• First Posted: October 12, 2011
• Study Start: June 24, 2014
• Primary Completion: April 13, 2017
• Study Completion: April 21, 2017
• Last Updated: June 26, 2018
• Results First Posted: June 26, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)