Clinical trial NCT03040726: 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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Malignant Neoplasm
Nausea
Vomiting
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Helsinn Healthcare SA
First posted: 2017-02-02
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Change in Nausea Numerical Rating Scale (NRS) Between Day 5 and Day 15
timeFrame: Day 5 and Day 15
Secondary outcomes:
measure: Functional Living Index Emesis (FLIE): Nausea Sub-score
timeFrame: Baseline and Day 15
measure: Functional Living Index Emesis (FLIE): Vomiting Sub-score
timeFrame: Baseline and Day 15
measure: Index of Nausea, Vomiting and Retching: Total Experience Score
timeFrame: Day 5 and Day 15
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: David Hui
role: PRINCIPAL_INVESTIGATOR
References:
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.