Rolapitant Hydrochloride and Ondansetron versus Ondansetron Monotherapy in Evaluating Efficacy, Patient Satisfaction, and Compliance in Patients with Malignant Glioma Undergoing Chemotherapy and Radiation Therapy

Status: Active

Description

This randomized phase II trial studies rolapitant hydrochloride and ondansetron versus ondansetron monotherapy in evaluating efficacy, patient satisfaction, and compliance in patients with malignant glioma undergoing chemotherapy and radiation therapy. Antiemetic drugs, such as rolapitant hydrochloride and ondansetron, may help lessen or prevent nausea and vomiting in patients treated with chemotherapy and radiation therapy.

Eligibility Criteria

Inclusion Criteria

  • Patients must have histologically-confirmed, newly-diagnosed malignant glioma (glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic pleomorphic xanthoastrocytoma, or anaplastic oligodendroglioma) and are scheduled to receive radiotherapy (for a total of 54-60 Gy) and concomitant daily temozolomide therapy (at a dose of 75 mg/m^2 for one complete 6-week cycle)
  • Karnofsky performance score >= 60% or Eastern Cooperative Oncology Group (ECOG) 0-2
  • For patients on higher than physiological level of corticosteroids, they must have been on a stable dose for 1 week prior to initiating study drug, and the dose should not be escalated over entry dose level, if clinically possible
  • Ability and willingness to give informed consent
  • Female patients of childbearing potential must have a negative pregnancy test at screening
  • Female patients of childbearing potential must agree to use an acceptable method of birth control from the signing of informed consent form and to continue its use during the study and for at least 90 days after the final dose
  • Male patients must agree to use an acceptable form of birth control from study day 1 through at least 90 days after the final dose
  • Hematocrit >= 29%
  • Absolute neutrophil count (ANC) >= 1,000 cells/mm^3
  • Platelets >= 100,000 cells/mm^3
  • Serum creatinine =< 1.4 mg/dl
  • Bilirubin < 1.5 times upper limit of normal
  • Aspartate aminotransferase (AST) =< 2.5 x upper limit of normal range (ULN); for subjects with known liver metastases =< 5 x ULN, and alanine aminotransferase (ALT) =< 2.5 x ULN; for subjects with known liver metastases =< 5 x ULN

Exclusion Criteria

  • Co-medications that may interact with rolapitant as reviewed by Duke Preston Robert Tisch Brain Tumor investigator pharmacist
  • Co-medications that are contraindicated in patients on rolapitant including pimozide, thioridazine, carbamazepine, colchicine, dabigatran (Pradaxa), edoxaban (Savaysa), fosphenytoin, metoprolol, phenobarbital, phenytoin, primidone, and warfarin
  • Inability or unwillingness to cooperate with the study procedures
  • Prophylactic medication for the prevention of nausea and vomiting 24 hours prior to the start of radiation therapy through the full course of radiation therapy is prohibited, with the exception of the study drug; corticosteroids will be allowed for treatment of cerebral swelling
  • Ongoing vomiting from any organic etiology
  • Previous participation in any clinical trial involving rolapitant
  • Received rolapitant within 21 days prior to study enrollment
  • Prior cancer chemotherapy or radiotherapy
  • Any current treatment, medical history, or uncontrolled condition, other than malignancy, (e.g., alcoholism or signs of alcohol abuse, seizure disorder, medical or psychiatric condition) that, in the opinion of the investigator, would confound the results of the study or pose any unwarranted risk in administering study drug to the subject
  • Patient has a known hypersensitivity to the administration of rolapitant or its excipients
  • Patient has a history of severe renal or hepatic impairment, severe bone marrow suppression, or systemic infection
  • Patient is a woman with a positive serum pregnancy test at screening, is pregnant, breast-feeding, or is planning to conceive children within the projected duration of the study treatment
  • Patient has taken the following agents within the last 48 hours prior to the start of treatment with study drug: * 5-hydroxytryptamine (HT3) antagonists (ondansetron, granisetron, dolasetron, tropisetron, etc.) * Benzamides (metoclopramide, alizapride, etc.) * Domperidone * Cannabinoids * Neurokinin-1 (NK1) antagonist (aprepitant) * Benzodiazepines (lorazepam, alprazolam, etc.) * Herbal medications or preparations in doses designed to ameliorate nausea or emesis
  • Patient has taken phenothiazines (prochlorperazine, fluphenazine, perphenazine, thiethylperazine, chlorpromazine, etc.) for any indication within the last 48 hours prior to the start of treatment with study drug
  • Palonosetron is not permitted within 7 days prior to administration of investigational product
  • Any vomiting, retching, dry heaves, or clinically significant nausea (i.e., National Cancer Institute [NCI] Common Toxicity Criteria version 4.0 grade 2-4 nausea) caused by any etiology in the 24 hrs. preceding day 1 of the study intervention (ondansetron or ondansetron with rolapitant) as scheduled to begin on day 1 of radiation and chemotherapy; or a patient who has a history of anticipatory nausea and vomiting
  • Patient must not have been dosed with test drug or blinded study drug in another investigational study within 30 days or 5 half-lives of the biologic activity of the test drug, whichever is longer, before the time of first study dose
  • Patient who is receiving investigational agent(s) as part of another clinical study at the time of screening or who anticipates receiving investigational agent(s) during their scheduled radiotherapy and concomitant daily temozolomide therapy

Locations & Contacts

North Carolina

Durham
Duke University Medical Center
Status: Active
Contact: Mary L. Affronti
Phone: 919-684-6239
Email: affro002@mc.duke.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. Compare the efficacy of rolapitant hydrochloride (rolapitant) plus ondansetron versus (vs.) ondansetron monotherapy in the prevention of nausea and vomiting, as measured by the overall complete response (CR) rate among malignant glioma patients during radiation therapy (RT) and concomitant temozolomide (TMZ).

SECONDARY OBJECTIVES:

I. Assess whether malignant glioma patients receiving RT and concomitant TMZ are more satisfied with rolapitant plus ondansetron vs. ondansetron monotherapy for the prevention of radiation-induced nausea and vomiting (RINV).

II. Describe the rationale behind a patient’s satisfaction with antiemetic preference based upon effectiveness, convenience and global satisfaction.

III. Compare the efficacy of rolapitant plus ondansetron vs. ondansetron monotherapy in the prevention of nausea and vomiting separately, as measured by the respective chemotherapy-induced nausea (CIN), chemotherapy-induced vomiting (CIV) -CR rates, among malignant glioma patients during RT and concomitant TMZ.

IV. Evaluate patient compliance with rolapitant plus ondansetron and ondansetron monotherapy.

V. Assess the safety of rolapitant plus ondansetron in the prevention of RINV in primary glioma patients receiving RT and concomitant TMZ.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive ondansetron orally (PO) daily for weeks 1-6 and rolapitant hydrochloride PO on day 22.

ARM B: Patients receive rolapitant hydrochloride PO on day 1 and ondansetron PO daily for weeks 1-6.

After completion of study treatment, patients are followed up for 2 weeks or at least 30 days.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Prevention

Lead Organization

Lead Organization
Duke University Medical Center

Principal Investigator
Mary L. Affronti

Trial IDs

Primary ID Pro00076418
Secondary IDs NCI-2017-01551
Clinicaltrials.gov ID NCT02991456