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

NCT02991456 | Completed Phase 2 Results FDA Drug

• 1 other identifier: Pro00076418
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Chemo-radiation Induced Nausea and Vomiting

Keywords

malignant glioma; temozolomide; temodar; radiation; emesis; nausea; vomiting; chemotherapy; Affronti; Peters; 00076418

Outcome Measures

Primary Outcomes (2)

• Complete Response (CR) Rate as Measured by Antiemesis Tool (MAT)

  The Complete Response rate is defined as the proportion of participants 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).

  Weeks 1 and 2

• Complete Response (CR) Rate as Measured by MAT With Supplemental Nurses Notes

  The Complete Response rate is defined as the proportion of participants 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) MAT and nurse notes if MATs are missing.

  Weeks 1 and 2

Secondary Outcomes (16)

• Number of Participants Preferring Rolapitant in Combination With Ondansetron Versus Ondansetron Alone

  Weeks 1-6

• Week 3 Patient Satisfaction: Effectiveness

  Weeks 1-3

• Week 3 Patient Satisfaction: Convenience

  Weeks 1-3

• Week 3 Patient Satisfaction: Overall Satisfaction

  Weeks 1-3

• Week 6 Patient Satisfaction: Effectiveness

  Weeks 4-6

Study Arms (2)

Sequence A

ACTIVE COMPARATOR

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; Drug: Ondansetron

Sequence B

ACTIVE COMPARATOR

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; Drug: Ondansetron

Interventions

Rolapitant DRUG

single 180 mg dose by mouth

Also known as: Varubi

Sequence A; Sequence B

Ondansetron DRUG

8 mg by mouth daily

Also known as: Zofran

Sequence A; Sequence B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• HT3 antagonists (ondansetron, granisetron, dolasetron, tropisetron, etc.).

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

The Preston Robert Tisch Brain Tumor Center at Duke

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center at Duke

MeSH Terms

Conditions

Vomiting; Glioma; Nausea

Interventions

rolapitant; Ondansetron

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: James Herndon II, Ph.D.
• Organization: Duke University

james.herndon@duke.edu

919-668-8145

Study Officials

• Mary Lou Affronti, DNP, RN, ANP, MHSc

  The Preston Robert Tisch Brain Tumor Center at Duke

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2016
• First Posted: December 13, 2016
• Study Start: October 9, 2017
• Primary Completion: May 9, 2022
• Study Completion: June 20, 2022
• Last Updated: July 11, 2023
• Results First Posted: July 11, 2023

Record last verified: 2023-07

Locations

US (1)