Rolapitant as an Antiemetic in Malignant Glioma Patients Receiving Radiotherapy and Temozolomide
Condition: Chemo-radiation Induced Nausea and Vomiting
MeSH terms: Glioma; Nausea; Vomiting
Intervention: Rolapitant; Ondansetron
Intervention description: single 180 mg dose by mouth; 8 mg by mouth daily
Intervention MeSH terms: Ondansetron; Rolapitant
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: malignant glioma; temozolomide; temodar; radiation; emesis; nausea; vomiting; chemotherapy; Affronti; Peters; 00076418

Summary:

      The purpose of this phase 2 study is to assess the efficacy and patient satisfaction of oral
      rolapitant plus ondansetron vs. oral ondansetron monotherapy in malignant glioma (MG)
      patients receiving standard of care radiation (RT) and temozolomide (TMZ) therapy. This is a
      randomized phase 2 trial of rolapitant plus ondansetron vs. ondansetron monotherapy for the
      prevention of chemo-radiation induced nausea and vomiting in primary MG subjects receiving RT
      and concomitant multi-dose TMZ.
    

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).

          -  Age ≥ 18 years

          -  Karnofsky ≥ 60% or ECOG 0-2

          -  Hematocrit >29%, Absolute Neutrophil Count >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 (ULN)

          -  Aspartate aminotransferase (AST) ≤ 2.5 x 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

          -  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 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

        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

          -  Previous participation in any clinical trial involving rolapitant

          -  Any vomiting, retching, dry heaves, or clinically significant nausea (i.e., 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.

          -  Ongoing vomiting from any organic etiology

          -  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-HT3 antagonists (ondansetron, granisetron, dolasetron, tropisetron, etc.).

          -  Benzamides (metoclopramide, alizapride, etc.)

          -  Domperidone

          -  Cannabinoids

          -  Natural Killer (NK)-1 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

          -  Patient must not have been dosed with a 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 (Any exception
             to this criteria will be noted in a study Memo to File)