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

M.D. Anderson Cancer Center

Status and phase: Completed; Phase 3; Phase 2

Conditions: Vomiting; Nausea; Malignant Neoplasm

Treatments: Drug: Palonosetron Hydrochloride; Other: Placebo; Other: Questionnaire Administration; Drug: Netupitant; Drug: Palonosetron

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT03040726

2016-0843 (Other Identifier)

NCI-2017-00599 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 53 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

53 participants in 2 patient groups, including a placebo group

Group I (netupitant, palonosetron hydrochloride)

Experimental group

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.

Treatment:

Drug: Palonosetron

Drug: Netupitant

Other: Questionnaire Administration

Drug: Palonosetron Hydrochloride

Group II (placebo)

Placebo Comparator group

Description:

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

Treatment:

Other: Placebo

Other: Questionnaire Administration