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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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Nausea, Vomiting, Glioma

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Trial Information

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


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 Ondansetron treatment with or without Aprepitant.


Inclusion Criteria:



- Patients must have histologically confirmed diagnosis of glioma glioblastoma
multiforme, gliosarcoma or anaplastic astrocytoma, or anaplastic oligodendroglioma,
oligodendroglioma) who are either chemotherapy naïve or non-naïve and scheduled to
receive temozolomide-based +/- Avastin- based chemotherapy. Patients with recurrent
disease whose diagnostic pathology confirmed glioma (glioblastoma multiforme,
gliosarcoma or anaplastic astrocytoma, or anaplastic oligodendroglioma,
oligodendroglioma) will not need re-biopsy.

- Age ≥ 18 years

- ≤ 2 prior chemotherapeutic regimens

- Patient is scheduled to receive temozolomide at 200mg/m2 po X 5 days out of a 28 day
cycle +/- Avastin 10 mg/kg X1 dose every two weeks.

- Study participation can occur for any planned 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 qd and the dose
should not be escalated over entry dose level, if clinically possible. The dose of
dexamethasone will be reduced by 50% to avoid drug to drug interactions with
Aprepitant.

- 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:

- 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: CYP3A4 enzyme inducers and 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

- Receiving maintenance decadron dose > 4mg qd

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Proportion of patients achieving an acute and delayed complete response (CR)

Outcome Description:

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. CR is defined for delayed CINV as no emetic episode and no use of rescue anti-nausea medication on study days 2-5.

Outcome Time Frame:

5 days

Safety Issue:

No

Principal Investigator

Mary Lou Affronti, RN, MSN, ANP, MHSc

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University

Authority:

United States: Food and Drug Administration

Study ID:

Pro00031206

NCT ID:

NCT01450826

Start Date:

December 2012

Completion Date:

March 2015

Related Keywords:

  • Nausea
  • Vomiting
  • Glioma
  • Chemotherapy induced nausea and vomiting
  • CINV
  • Glioma
  • Temozolomide
  • Temodar
  • Aprepitant
  • Emend
  • Ondansetron
  • Zofran
  • Pro00031206
  • Affronti
  • Vredenburgh
  • Duke
  • Preston Robert Tisch Brain Tumor Center
  • Glioma
  • Nausea
  • Vomiting

Name

Location

The Preston Robert Tisch Brain Tumor Center at DukeDurham, North Carolina  27710