MedPath

Netupitant and Palonosetron Hydrochloride in Preventing Chronic Nausea and Vomiting in Patients With Cancer

Phase 2
Completed
Conditions
Vomiting
Malignant Neoplasm
Nausea
Interventions
Other: Placebo
Other: Questionnaire Administration
Registration Number
NCT03040726
Lead Sponsor
M.D. Anderson Cancer Center
Brief Summary

This randomized phase II/III trial studies how well netupitant and palonosetron hydrochloride works in preventing chronic nausea and vomiting in patients with cancer. Netupitant and palonosetron hydrochloride may reduce nausea and vomiting.

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate the efficacy (i.e. change in nausea numeric rating scale \[NRS\] from baseline between day 5-15) of fixed dose netupitant and palonosetron hydrochloride (palonosetron) (NEPA) for chronic nausea in cancer patients.

SECONDARY OBJECTIVES:

I. To assess the secondary outcomes (e.g. proportion of patients who achieved their personalized nausea goal, antiemetic use, nausea episodes duration/frequency) for NEPA versus (vs.) placebo.

II. To assess the adverse effects associated with NEPA and placebo.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients receive netupitant orally (PO) and palonosetron hydrochloride PO on days 1, 6, and 11 in the absence of disease progression or unacceptable toxicity.

GROUP II: Patients receive placebo PO on days 1, 6, and 11.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
53
Inclusion Criteria
  • Diagnosis of cancer
  • Chronic nausea over the past 4 weeks
  • Average nausea numeric rating scale >= 4/10 over the past 5 days at screening
  • Outpatient at MD Anderson Cancer Center
  • Karnofsky performance status >= 50%
  • Age 18 or older
  • Able to complete study assessments, including keeping a daily diary
Exclusion Criteria
  • Delirium (i.e. Memorial Delirium Rating Scale > 13)

  • Clinical evidence of bowel obstruction at the time of study enrollment

  • Expected to use other 5HT3 antagonists or NK1 antagonists for prophylaxis during the study

  • Continuation of over-the-counter therapies for nausea and/or vomiting during the study

  • On cytotoxic chemotherapy in the high/moderate/low emetogenic risk categories or oral antineoplastic agents in the high or moderate emetogenic risk categories according to the latest National Comprehensive Cancer Network (NCCN) guideline within 2 weeks of study enrollment

  • On scheduled potent CYP3A4 inducers at the time of study enrollment (avasimibe, carbamazepine, phenytoin, rifampin, efavirenz, nevirapine, barbiturates, systemic glucocorticoids, modafinil, oxcarbazine, phenobarbital, pioglitazone, rifabutin, St. John's wort, troglitazone)

  • On scheduled CYP3A4 substrates with narrow safety range at the time of study enrollment (alfentanil, cyclosporine, dihydroergotamine, ergotamine, pimozide, quinidine, sirolimus, tacrolimus)

  • On scheduled strong or moderate CYP3A4 inhibitors (boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole; amprenavir, aprepitant, atazanavir, ciprofloxacin, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil) within one week of study enrollment

  • Unwilling to provide informed consent

  • Severe renal impairment (calculated creatinine clearance =< 29 cc/min)

    • Calculated creatinine clearance can be done within 14 days of study enrollment
  • Severe liver impairment (Child-Pugh score > 9)

    • Total (T.) bilirubin, albumin, prothrombin time, and serum creatinine tests can be done within 14 days of study enrollment (only if not performed in the last 14 days)
  • Females who are pregnant, lactating, or intend to become pregnant during the participation of the study; childbearing age women who are not on birth control; positive pregnancy test for women of childbearing potential, as defined by intact uterus and ovaries, and no history of menses within the last 12 months; pregnancy test to be performed on the day of enrollment; in cases of women with elevated beta-human chorionic gonadotropin (b-HCG), these candidates will be eligible to participate so long as the level of b-HCG is not consistent with pregnancy and the non-pregnant status is confirmed by a gynecologic examination

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group I (netupitant, palonosetron hydrochloride)Palonosetron HydrochloridePatients receive netupitant orally (PO) and palonosetron hydrochloride PO on days 1, 6, and 11 in the absence of disease progression or unacceptable toxicity.
Group I (netupitant, palonosetron hydrochloride)Questionnaire AdministrationPatients receive netupitant orally (PO) and palonosetron hydrochloride PO on days 1, 6, and 11 in the absence of disease progression or unacceptable toxicity.
Group II (placebo)Questionnaire AdministrationPatients receive placebo PO on days 1, 6, and 11.
Group II (placebo)PlaceboPatients receive placebo PO on days 1, 6, and 11.
Group I (netupitant, palonosetron hydrochloride)PalonosetronPatients receive netupitant orally (PO) and palonosetron hydrochloride PO on days 1, 6, and 11 in the absence of disease progression or unacceptable toxicity.
Group I (netupitant, palonosetron hydrochloride)NetupitantPatients receive netupitant orally (PO) and palonosetron hydrochloride PO on days 1, 6, and 11 in the absence of disease progression or unacceptable toxicity.
Primary Outcome Measures
NameTimeMethod
Change in Nausea Numerical Rating Scale (NRS) Between Day 5 and Day 15Day 5 and Day 15

Average intensity of nausea over the past 24 hours was assessed daily using a validated numeric rating scale from 0 to 10, where 0= none and 10= worse possible nausea. The total score ranged from 0-10. We measured the within-group change in nausea intensity from day 5 to day 15. Wilcoxon rank sum test was used for analysis.

Secondary Outcome Measures
NameTimeMethod
Functional Living Index Emesis (FLIE): Nausea Sub-scoreBaseline and Day 15

FLIE is a questionnaire validated to assess the impact of chemotherapy induced nausea and vomiting on patient's function and quality of life over the past 5 days. It consists of 18 items, with 9 items on nausea and 9 items on vomiting. Each question was rated using a Numerical Rating Scale (NRS) from 1 to 7. The total Nausea sub-score ranges from 9 to 63, where a higher score indicates higher quality of life. We measured the change of nausea sub-score between baseline 5 to day 15. Wilcoxon rank sum test was used for analysis.

Functional Living Index Emesis (FLIE): Vomiting Sub-scoreBaseline and Day 15

FLIE is a questionnaire validated to assess the impact of chemotherapy induced nausea and vomiting on patient's function and quality of life over the past 5 days. It consists of 18 items, with 9 items on nausea and 9 items on vomiting. Each question was rated using a Numerical Rating Scale (NRS) from 1 to 7. The total Vomiting sub-score ranges from 9 to 63, where a higher score indicates higher quality of life. We measured the change of vomiting sub-score from baseline to day 15.Wilcoxon rank sum test was used for analysis.

Index of Nausea, Vomiting and Retching: Total Experience ScoreDay 5 and Day 15

Index of Nausea, Vomiting, and Retching, which consists of 8 items asking about the patient's experience regarding nausea and vomiting over the past 12 hours. Each item included a 5-point Likert scale (0-4 points) with descriptive words. Total experience score ranged from 0-32 with higher score indicates more nausea/vomiting. We measured the change in score between day 5 and day 15. Wilcoxon rank sum test was used for analysis.

Trial Locations

Locations (1)

M D Anderson Cancer Center

🇺🇸

Houston, Texas, United States

© Copyright 2025. All Rights Reserved by MedPath