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

Primary Purpose

Malignant Neoplasm, Nausea, Vomiting

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Netupitant
Palonosetron
Palonosetron Hydrochloride
Placebo
Questionnaire Administration
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Malignant Neoplasm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Group I (netupitant, palonosetron hydrochloride)

Group II (placebo)

Arm Description

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

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

Outcomes

Primary Outcome Measures

Change in Nausea Numerical Rating Scale (NRS) Between Day 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

Functional Living Index Emesis (FLIE): Nausea Sub-score
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-score
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 Score
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.

Full Information

First Posted
January 31, 2017
Last Updated
September 25, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI), Helsinn Healthcare SA
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1. Study Identification

Unique Protocol Identification Number
NCT03040726
Brief Title
Netupitant and Palonosetron Hydrochloride in Preventing Chronic Nausea and Vomiting in Patients With Cancer
Official Title
Fixed-Dose Netupitant and Palonosetron for Chronic Nausea and Vomiting in Cancer Patients
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
May 3, 2017 (Actual)
Primary Completion Date
February 14, 2022 (Actual)
Study Completion Date
February 14, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI), Helsinn Healthcare SA

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Neoplasm, Nausea, Vomiting

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
53 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group I (netupitant, palonosetron hydrochloride)
Arm Type
Experimental
Arm Description
Patients receive netupitant orally (PO) and palonosetron hydrochloride PO on days 1, 6, and 11 in the absence of disease progression or unacceptable toxicity.
Arm Title
Group II (placebo)
Arm Type
Placebo Comparator
Arm Description
Patients receive placebo PO on days 1, 6, and 11.
Intervention Type
Drug
Intervention Name(s)
Netupitant
Other Intervention Name(s)
CID6451149, D05152, RO 67-3189/000
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Palonosetron
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Palonosetron Hydrochloride
Other Intervention Name(s)
Aloxi, RS 25259-197
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
placebo therapy, PLCB, sham therapy
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Change in Nausea Numerical Rating Scale (NRS) Between Day 5 and Day 15
Description
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.
Time Frame
Day 5 and Day 15
Secondary Outcome Measure Information:
Title
Functional Living Index Emesis (FLIE): Nausea Sub-score
Description
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.
Time Frame
Baseline and Day 15
Title
Functional Living Index Emesis (FLIE): Vomiting Sub-score
Description
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.
Time Frame
Baseline and Day 15
Title
Index of Nausea, Vomiting and Retching: Total Experience Score
Description
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.
Time Frame
Day 5 and Day 15

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Hui
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
33388382
Citation
Hui D, Puac V, Shelal Z, Liu D, Maddi R, Kaseb A, Javle M, Overman M, Yennurajalingam S, Gallagher C, Bruera E. Fixed-Dose Netupitant and Palonosetron for Chronic Nausea in Cancer Patients: A Double-Blind, Placebo Run-in Pilot Randomized Clinical Trial. J Pain Symptom Manage. 2021 Aug;62(2):223-232.e1. doi: 10.1016/j.jpainsymman.2020.12.023. Epub 2021 Jan 1.
Results Reference
derived
Links:
URL
http://www.mdanderson.org
Description
University of Texas MD Anderson Cancer Center Website

Learn more about this trial

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

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