Emend and Ondansetron Compared to Ondansetron Alone to Prevent CINV in Glioma Patients Receiving Temozolomide
Condition: Nausea; Vomiting; Glioma
MeSH terms: Glioma; Nausea; Vomiting
Intervention: aprepitant; ondansetron
Intervention description: 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).; 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 MeSH terms: Ondansetron; Aprepitant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 136.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chemotherapy induced nausea and vomiting; CINV; Glioma; Temozolomide; Temodar; Aprepitant; Emend; Ondansetron; Zofran; Pro00031206; Affronti; Peters; Duke; Preston Robert Tisch Brain Tumor Center

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.
    

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