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

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ClinicalTrials.gov Identifier: NCT02991456
Recruitment Status : Recruiting
First Posted : December 13, 2016
Last Update Posted : June 4, 2019
Sponsor:
Collaborator:
TerSera Therapeutics
Information provided by (Responsible Party):
Duke University

Brief 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.

Condition or disease Intervention/treatment Phase
Chemo-radiation Induced Nausea and Vomiting Drug: Rolapitant Drug: Ondansetron Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Phase II Randomized Study to Evaluate Efficacy, Patient Satisfaction, and Compliance of the Oral Combination of Rolapitant (Varubi®) Plus Ondansetron vs. Ondansetron Monotherapy in Malignant Glioma Patients Receiving Radiotherapy (RT) and Concomitant Temozolomide
Actual Study Start Date : October 9, 2017
Estimated Primary Completion Date : March 15, 2021
Estimated Study Completion Date : April 27, 2021


Arm Intervention/treatment
Active Comparator: Sequence A
Daily ondansetron alone for 3 weeks, followed by the use of rolapitant (one dose on day 22) plus continued daily ondansetron for 3 weeks.
Drug: Rolapitant
single 180 mg dose by mouth
Other Name: Varubi

Drug: Ondansetron
8 mg by mouth daily
Other Name: Zofran

Active Comparator: Sequence B
Single dose of rolapitant (one dose on day 1) plus daily ondansetron for 3 weeks, followed by daily ondansetron alone for 3 weeks.
Drug: Rolapitant
single 180 mg dose by mouth
Other Name: Varubi

Drug: Ondansetron
8 mg by mouth daily
Other Name: Zofran




Primary Outcome Measures :
  1. Complete response (CR) rate [ Time Frame: 2 weeks ]
    The Complete Response rate is defined as the percentage of patients with no emetic episode or the use of rescue medication during the first two weeks of radiation therapy and concomitant Temozolomide. The Complete Response rate will be assessed via the modified Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool (MAT).


Secondary Outcome Measures :
  1. Percentage of patients preferring rolapitant in combination with ondansetron versus ondansetron alone [ Time Frame: 6 weeks ]
    The percentage of patients who prefer rolapitant plus ondansetron over ondansetron alone, as determined by response to the question with "Which nausea medication regimen was I most satisfied with?"

  2. Ondansetron monotherapy patient satisfaction: Effectiveness [ Time Frame: Weeks 1-3 for Sequence A; Weeks 4-6 for Sequence B ]
    Mean effectiveness scores for ondansetron monotherapy using the 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) patient satisfaction survey. The effectiveness subscale score will be computed by summing the 3 items corresponding to effectiveness.

  3. Ondansetron + rolapitant patient satisfaction: Effectiveness [ Time Frame: Weeks 4-6 for Sequence A; Weeks 1-3 for Sequence B ]
    Mean effectiveness scores for ondansetron + rolapitant combination therapy using the 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) patient satisfaction survey. The effectiveness subscale score will be computed by summing the 3 items corresponding to effectiveness.

  4. Ondansetron monotherapy patient satisfaction: Convenience [ Time Frame: Weeks 1-3 for Sequence A; Weeks 4-6 for Sequence B ]
    Mean convenience scores for ondansetron monotherapy using the 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) patient satisfaction survey. The convenience subscale score will be computed by summing the 3 items corresponding to convenience.

  5. Ondansetron + rolapitant patient satisfaction: Convenience [ Time Frame: Weeks 4-6 for Sequence A; Weeks 1-3 for Sequence B ]
    Mean convenience scores for ondansetron + rolapitant combination therapy using the 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) patient satisfaction survey. The convenience subscale score will be computed by summing the 3 items corresponding to convenience.

  6. Ondansetron monotherapy patient satisfaction: Global satisfaction [ Time Frame: Weeks 1-3 for Sequence A; Weeks 4-6 for Sequence B ]
    Mean global satisfaction scores for ondansetron monotherapy using the 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) patient satisfaction survey. The global satisfaction subscale score will be computed by summing the 3 items corresponding to global satisfaction.

  7. Ondansetron + rolapitant patient satisfaction: Global satisfaction [ Time Frame: Weeks 4-6 for Sequence A; Weeks 1-3 for Sequence B ]
    Mean global satisfaction scores for ondansetron + rolapitant combination therapy using the 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) patient satisfaction survey. The global satisfaction subscale score will be computed by summing the 3 items corresponding to global satisfaction.

  8. Chemotherapy-induced nausea (CIN) CR Rate for ondansetron monotherapy [ Time Frame: Weeks 1-3 for Sequence A; Weeks 4-6 for Sequence B ]
    The CIN CR rate is defined as the percentage of patients with no use of rescue medication for nausea. The CIN CR rates will be assessed via the modified Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool (MAT).

  9. Chemotherapy-induced nausea (CIN) CR Rate for ondansetron + rolapitant [ Time Frame: Weeks 4-6 for Sequence A; Weeks 1-3 for Sequence B ]
    The CIN CR rate is defined as the percentage of patients with no use of rescue medication for nausea. The CIN CR rates will be assessed via the modified MASCC Antiemesis Tool (MAT).

  10. Chemotherapy-induced vomiting (CIV) CR Rate for ondansetron monotherapy [ Time Frame: Weeks 1-3 for Sequence A; Weeks 4-6 for Sequence B ]
    The CIV CR rate is defined as the percentage of patients with no use of rescue medication for vomiting. The CIV CR rates will be assessed via the modified MASCC Antiemesis Tool (MAT).

  11. Chemotherapy-induced vomiting (CIV) CR Rate for ondansetron + rolapitant [ Time Frame: Weeks 4-6 for Sequence A; Weeks 1-3 for Sequence B ]
    The CIV CR rate is defined as the percentage of patients with no use of rescue medication for vomiting. The CIV CR rates will be assessed via the modified MASCC Antiemesis Tool (MAT).

  12. Ondansetron monotherapy medication compliance [ Time Frame: Weeks 1-3 for Sequence A; Weeks 4-6 for Sequence B ]
    Medication compliance is defined as the mean percentage of days that ondansetron alone was appropriately used during the six weeks.

  13. Ondansetron + rolapitant medication compliance [ Time Frame: Weeks 4-6 for Sequence A; Weeks 1-3 for Sequence B ]
    Medication compliance is defined as the mean percentage of days that ondansetron + rolapitant were appropriately used during the six weeks.

  14. Percentage of participants with grade 3, 4 or 5 treatment-related adverse events [ Time Frame: 8 weeks ]
    The percentage of participants with grade 3, 4 or 5 adverse events possibly, probably or definitely related to administration of Rolapitant or Ondansetron. Adverse events will be collected from start of treatment through the end of the two-week period following chemoradiation (or until 30 days after the last dose of rolapitant is given in Sequence A).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02991456


Contacts
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Contact: Mary Lou Affronti, DNP, RN, ANP, MHSc 919-684-5301 dukebrain1@dm.duke.edu
Contact: Edy Parker 919-684-5301

Locations
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United States, North Carolina
The Preston Robert Tisch Brain Tumor Center at Duke Recruiting
Durham, North Carolina, United States, 27710
Contact: Mary Lou Affronti, DNP, RN, ANP, MHSc    919-684-5301      
Contact: Edythe Parker, BS, MBA    919-684-5301      
Principal Investigator: Katherine Peters, MD, PhD         
Sponsors and Collaborators
Duke University
TerSera Therapeutics
Investigators
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Principal Investigator: Mary Lou Affronti, DNP, RN, ANP, MHSc The Preston Robert Tisch Brain Tumor Center at Duke

Additional Information:
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Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT02991456     History of Changes
Other Study ID Numbers: Pro00076418
First Posted: December 13, 2016    Key Record Dates
Last Update Posted: June 4, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Duke University:
malignant glioma
temozolomide
temodar
radiation
emesis
nausea
vomiting
chemotherapy
Affronti
Peters
00076418

Additional relevant MeSH terms:
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Glioma
Nausea
Vomiting
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Signs and Symptoms, Digestive
Signs and Symptoms
Temozolomide
Ondansetron
8-((1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)methyl)-8-phenyl-1,7-diazaspiro(4,5)decan-2-one
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Antipruritics
Dermatologic Agents
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Antipsychotic Agents