Patient case: 82-year-old male with glioma; genetic feature: BRAF

Clinical trial: Rolapitant as an Antiemetic in Malignant Glioma Patients Receiving Radiotherapy and Temozolomide

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.

Detailed description: All eligible subjects should receive a planned total dose of 54-60 gray (GY) of radiation and 75 mg/m2 of TMZ daily for a total of six weeks. Patients will be randomized to receive one of two antiemetic treatment sequences: sequence A that involves administration of ondansetron alone for 3 weeks followed by a single dose of rolapitant (day 22) plus daily ondansetron for 3 weeks or sequence B that involves a single dose of rolapitant (day 1) plus daily ondansetron for 3 weeks followed by 3 weeks of daily ondansetron alone. The study has one primary endpoint: complete response (CR) rate. Participation in this study may result in reduced chemo-radiation induced nausea and vomiting, however, risks include the common side effects of rolapitant including decreased appetite, neutropenia, dizziness, dyspepsia, urinary tract infection, stomatitis, and anemia.

Eligibility: 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/m2 for one complete 6-week cycle).
  -  Age ≥ 18 years
  -  Karnofsky ≥ 60%
  -  Hematocrit >29%, Absolute Neutrophil Count >1,000 cells/mm3, platelets >100,000 cells/mm3
  -  Serum creatinine <1.4 mg/dl, serum glutamic oxaloacetic transaminase (SGOT) and 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
  -  If sexually active, patients will take contraceptive measures for the duration of the treatments
  -  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 for 72 hours prior to start of radiation 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-medication that may interfere with study results; e.g., immune-suppressive agents other than corticosteroids
  -  Co-medications that may interact with rolapitant (e.g. metoprolol/beta blocker, codeine, pimozide thioridazine) as reviewed by Duke Preston Robert Tisch Brain Tumor investigator pharmacist.
  -  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, or National Cancer Institute (NCI) Common Toxicity Criteria version 4.0 grade 2-4 nausea in the 24 hrs. preceding radiation and chemotherapy
  -  Ongoing vomiting from any organic etiology
  -  Radiotherapy of abdomen within one week prior to or during the study
  -  Received rolapitant within 21 days prior to study enrollment
  -  Prior cancer chemotherapy and 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 urine or 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.). Palonosetron is not permitted within 7 days prior to administration of investigational product
  -  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
  -  Patient has ongoing vomiting, retching, dry heaves, or clinically significant nausea caused by any etiology, or has had such symptoms within 24 hours prior to the start of Day 1 of the study intervention, or has a history of anticipatory nausea and vomiting
  -  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 participating in any other clinical study including investigational agents (e.g. magnesium porphyrin study)

Relevance to patient case: not relevant