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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Duke University
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Katy Peters, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01450826
First received: October 10, 2011
Last updated: September 2, 2014
Last verified: September 2014
  Purpose

The objectives of the study are: 1) Primary: Assess CINV efficacy of Aprepitant in combination with Ondansetron vs. Ondansetron alone in preventing acute and delayed CINV (Complete Control (CC): days 1-7) in brain tumor patients during adjuvant temozolomide therapy; and 2) Secondary: To assess the efficacy of Aprepitant in combination with Ondansetron vs Ondansetron alone in preventing acute CINV in brain tumor patients during the acute period (first 24 hours) of receiving adjuvant temozolomide therapy; 3)Secondary: To assess the efficacy of Aprepitant in combination with Ondansetron vs. Ondansetron alone in preventing delayed CINV (days 2-7); 4) Secondary: To assess the safety and tolerability of Aprepitant administered concomitantly with Ondansetron; 5) Exploratory: To assess the time to treatment failure of Ondansetron treatment with and without Aprepitant; 6) Exploratory: To explore the effects of age, gender, chemotherapy history, and concomitant glucocorticoid on the efficacy of Ondansetron treatment with and without Aprepitant; 7) Exploratory: To explore the impact of Aprepitant on quality of life and daily function.


Condition Intervention Phase
Nausea
Vomiting
Glioma
Drug: Aprepitant
Drug: Ondansetron
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Open Label Phase II Trial of Aprepitant (Emend) in Combination With Ondansetron Compared to Standard 5HT3 Serotonin Antagonist (Ondansetron) in the Prevention of Acute and Delayed Chemotherapy Induced Nausea and Vomiting (CINV) in Glioma Patients Receiving a Temozolomide Based Regimen

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Proportion of patients achieving an acute and delayed complete response (CR) [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    CR is the proportion of patients with no emetic episode and no rescue medication. (1) Assessed from the beginning of study day 1, CR is defined for acute CINV as no emetic episode and no use of rescue anti-nausea medication during the first 24 hours following chemotherapy administration. An emetic episode is defined as one episode of vomiting or a sequence of episodes in very close succession not relieved by a period of relaxation of at least 1 min, any number of unproductive emetic episodes (retches) in any given 5 minute period, or an episode of retching lasting <5 minutes combined with vomiting not relieved by a period of relaxation of at least 1 minute; (2) Complete response (CR) on study days 2-7 (delayed CINV) is defined as the proportion of patients achieving a CR during the delayed time period. The data will be captured by the validated MAT/Osoba survey.


Secondary Outcome Measures:
  • Proportion of patients achieving complete control (CC) [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    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).

  • Patient's global satisfaction with the antiemetic regimen [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Patient's global satisfaction with the antiemetic regimen as measured by the Osoba survey. This survey will be administered at baseline and for day 1 (acute period) and for days 2-7 (delayed period) to determine overall global satisfaction (Acute and delayed combined to determine overall CC, days 1-7).

  • Time to treatment failure [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    First emetic episode or first need of rescue medication, whichever occurred first as measured by the MAT/Osoba survey, which indicates time of first emetic episode or rescue medication.


Estimated Enrollment: 136
Study Start Date: December 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Emend (Aprepitant) and Ondansetron Regimen
Aprepitant in combination with Ondansetron on Days 1-5 of a 5-day oral temozolomide regimen
Drug: 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).
Other Name: Emend
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.
Other Name: Zofran
Active Comparator: Ondansetron Alone Regimen
Ondansetron alone on Days 1-5 of a 5-day oral temozolomide regimen
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.
Other Name: Zofran

Detailed Description:

One hundred and thirty-six (136) malignant glioma patients receiving temozolomide will be accrued in this open labeled phase II randomized single institution trial of Aprepitant in combination with Ondansetron vs. Ondansetron alone for the prevention of acute and delayed CINV. Sixty-eight (68) patients will be randomized to each arm of the study. Patient randomization will be stratified by grade (I/II vs. III/IV) and the number of prior progressions (0/1 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 Ondansetron with or without Aprepitant.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • The lab values following the prior chemotherapy must return within normal limits prior to study enrollment.
  • Karnofsky ≥ 60%.
  • Hematocrit > 29%, ANC > 1,000 cells/µl, platelets > 100,000 cells/µl
  • Serum creatinine < 1.5 mg/dl, serum SGOT and bilirubin < 1.5 times upper limit of normal
  • For patients on corticosteroids, they must have been on a stable dose for 1 week prior to entry. The dexamethasone dose should not exceed > 4 mg every day and the dose should not be escalated over entry dose level, if clinically possible. All doses of 4 mg and less dexamethasone will be reduced by 50% to avoid drug to drug interactions with Aprepitant. It is recommended that dexamethasone 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. Also, patients receiving a maintenance decadron dose > 4mg every day 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
  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: NCT01450826

Contacts
Contact: Mary Lou Affronti, DNP, RN, MSN, ANP, MHSc 919-684-6239 mary.affronti@duke.edu
Contact: Sarah Woodring 919-684-2527 sarah.woodring@duke.edu

Locations
United States, North Carolina
The Preston Robert Tisch Brain Tumor Center at Duke Recruiting
Durham, North Carolina, United States, 27710
Contact: Mary Lou Affronti, RN, MSN, ANP, MHSc    919-684-6239    mary.affronti@duke.edu   
Contact: Sarah Woodring    919-684-2527    sarah.woodring@duke.edu   
Principal Investigator: Mary Lou Affronti, DNP, RN, MSN, ANP, MHSc         
Principal Investigator: Katherine B Peter, MD, PhD         
Sponsors and Collaborators
Katy Peters
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Mary Lou Affronti, DNP, RN, MSN, ANP, MHSc Duke University
Principal Investigator: Katherine B Peters, MD, PhD Duke University
  More Information

Additional Information:
No publications provided

Responsible Party: Katy Peters, Assistant Professor, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01450826     History of Changes
Other Study ID Numbers: Pro00031206
Study First Received: October 10, 2011
Last Updated: September 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
Chemotherapy induced nausea and vomiting
CINV
Glioma
Temozolomide
Temodar
Aprepitant
Emend
Ondansetron
Zofran
Pro00031206
Affronti
Peters
Duke
Preston Robert Tisch Brain Tumor Center

Additional relevant MeSH terms:
Nausea
Vomiting
Glioma
Signs and Symptoms, Digestive
Signs and Symptoms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Ondansetron
Aprepitant
Fosaprepitant
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Antipruritics

ClinicalTrials.gov processed this record on September 22, 2014