Netupitant and Palonosetron Hydrochloride in Preventing Chronic Nausea and Vomiting in Patients With Cancer
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
PRIMARY OBJECTIVES:
- 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:
-
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.
-
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group I (netupitant, palonosetron hydrochloride) Patients receive netupitant orally (PO) and palonosetron hydrochloride PO on days 1, 6, and 11 in the absence of disease progression or unacceptable toxicity. |
Drug: Netupitant
Given PO
Other Names:
Drug: Palonosetron
Given PO
Drug: Palonosetron Hydrochloride
Given PO
Other Names:
Other: Questionnaire Administration
Ancillary studies
|
| Placebo Comparator: Group II (placebo) Patients receive placebo PO on days 1, 6, and 11. |
Other: Placebo
Given PO
Other Names:
Other: Questionnaire Administration
Ancillary studies
|
Outcome Measures
Primary Outcome Measures
- Change in nausea numeric rating scale [Day 5-15]
Descriptive statistics, including mean, standard deviation, 95% confidence intervals, median, range, frequency and percentage will be summarized. Will use a mixed model to examine the change in nausea overtime in both the netupitant and palonosetron hydrochloride arm and placebo arm. General linear model may be considered to examine the effect of potential important factors on nausea numeric rating scale.
Secondary Outcome Measures
- Proportion of patients who achieved their personalized nausea goal [Up to day 15]
Descriptive statistics, including mean, standard deviation, 95% confidence intervals, median, range, frequency and percentage will be summarized.
- Antiemetic use [Up to day 15]
Descriptive statistics, including mean, standard deviation, 95% confidence intervals, median, range, frequency and percentage will be summarized.
- Nausea episodes duration/frequency [Up to day 15]
Descriptive statistics, including mean, standard deviation, 95% confidence intervals, median, range, frequency and percentage will be summarized.
- Incidence of adverse events [Up to day 15]
Will be assessed by Common Terminology Criteria for Adverse Events. Will be collected and frequency will be summarized. Chi-squared test or Fisher's exact test, whichever the most appropriate, will be used to test for association between categorical variables, such as Common Terminology Criteria for Adverse Events adverse effects, between netupitant and palonosetron hydrochloride and placebo.
- Global assessment [Up to day 15]
Chi-squared test or Fisher's exact test, whichever the most appropriate, will be used to test for association between categorical variables, such as global assessment, between netupitant and palonosetron hydrochloride and placebo.
- Blinding [Up to day 15]
Chi-squared test or Fisher's exact test, whichever the most appropriate, will be used to test for association between categorical variables, such as blinding, between netupitant and palonosetron hydrochloride and placebo.
- Edmonton Symptom Assessment System [Up to day 15]
Wilcoxon rank sum test or Kruskal-Wallis test will be used to test for difference of continuous variables, such as Edmonton Symptom Assessment System between netupitant and palonosetron hydrochloride and placebo.
- Functional Living Index-Emesis questionnaire [Up to day 15]
Wilcoxon rank sum test or Kruskal-Wallis test will be used to test for difference of continuous variables, Functional Living Index-Emesis between netupitant and palonosetron hydrochloride and placebo.
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- National Cancer Institute (NCI)
- Helsinn Healthcare SA
Investigators
- Principal Investigator: David Hui, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2016-0843
- NCI-2017-00599
- 2016-0843