Malignant Neoplasm, Nausea, Vomiting
Conditions
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.
Interventions
DRUGNetupitant
Given PO
DRUGPalonosetron
Given PO
Given PO
OTHERPlacebo
Given PO
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
National Cancer Institute (NCI)
Helsinn Healthcare SA
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Nausea Numerical Rating Scale (NRS) Between Day 5 and Day 15 | 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
| Measure | Time frame | Description |
|---|---|---|
| Functional Living Index Emesis (FLIE): Nausea Sub-score | Baseline 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-score | Baseline 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 Score | Day 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. |
Countries
United States
Participant flow
Recruitment details
Cancer patients with age \>=18, chronic nausea over the past 4 weeks, an average nausea numeric rating scale (NRS) \>=4/10 over the past 5 days were recruited from the Supportive Care, Gastrointestinal Medical Oncology, Breast Medical Oncology, and the Gastroenterology, Hepatology and Nutrition clinics at the University of Texas MD Anderson Cancer Center.
Pre-assignment details
A total of 53 participants were enrolled but 46 were randomized. 7 participants were not randomized for various reasons that included Change in cancer treatment (n=3), Developed renal failure (n=1), Developed bowel obstruction (n=1) and Other (n=2)
Participants by arm
| Arm | Count |
|---|---|
| Blinded Intervention gp. Took one Netupitant/Palonosetron (NEPA) capsule every 5 days for 2 doses | 31 |
| Blinded Placebo gp. Took Placebo capsule every 5 days for 2 doses | 15 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Reasons for not completing Blinded phase: Hospitalization | 0 | 2 |
| Overall Study | Reasons for not completing Blinded phase : Withdrawal | 1 | 0 |
| Overall Study | Reasons for not completing Placebo run in phase: Nausea NRS score >4 | 4 | 3 |
| Overall Study | Reasons for not completing Placebo run in phase phase; Drop Out | 4 | 0 |
| Overall Study | Reasons for not completing Placebo run in phase phase; withdrawal | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Blinded Placebo gp. | Blinded Intervention gp. |
|---|---|---|---|
| Age, Continuous | 55 years | 52.7 years | 56.2 years |
| Cancer Stage Locally advanced | 21 Participants | 6 Participants | 15 Participants |
| Cancer Stage Metastatic | 24 Participants | 9 Participants | 15 Participants |
| Cancer Stage Recurrent or persistent | 1 Participants | 0 Participants | 1 Participants |
| Cancer Type Breast | 5 Participants | 1 Participants | 4 Participants |
| Cancer Type Gastrointestinal | 33 Participants | 12 Participants | 21 Participants |
| Cancer Type Genitourinary | 1 Participants | 0 Participants | 1 Participants |
| Cancer Type Gynaecological | 1 Participants | 1 Participants | 0 Participants |
| Cancer Type Hematology | 1 Participants | 0 Participants | 1 Participants |
| Cancer Type Other | 2 Participants | 1 Participants | 1 Participants |
| Cancer Type Respiratory | 3 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 4 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 11 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 33 Participants | 12 Participants | 21 Participants |
| Region of Enrollment United States | 46 Participants | 15 Participants | 31 Participants |
| Sex: Female, Male Female | 30 Participants | 7 Participants | 23 Participants |
| Sex: Female, Male Male | 16 Participants | 8 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 30 | 2 / 43 |
| other Total, other adverse events | 10 / 30 | 9 / 43 |
| serious Total, serious adverse events | 1 / 30 | 3 / 43 |
Outcome results
Primary
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.
Time frame: Day 5 and Day 15
Population: Those who completed Day 15
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Blinded Intervention Group | Change in Nausea Numerical Rating Scale (NRS) Between Day 5 and Day 15 | -2.0 score on a scale |
| Blinded Placebo Group | Change in Nausea Numerical Rating Scale (NRS) Between Day 5 and Day 15 | -2.3 score on a scale |
p-value: 0.98Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: Baseline and Day 15
Population: Those who completed Day 15
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Blinded Intervention Group | Functional Living Index Emesis (FLIE): Nausea Sub-score | -16.6 score on a scale |
| Blinded Placebo Group | Functional Living Index Emesis (FLIE): Nausea Sub-score | -18 score on a scale |
p-value: 0.4Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: Baseline and Day 15
Population: Those who completed Day 15
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Blinded Intervention Group | Functional Living Index Emesis (FLIE): Vomiting Sub-score | -12.5 score on a scale |
| Blinded Placebo Group | Functional Living Index Emesis (FLIE): Vomiting Sub-score | -9.7 score on a scale |
p-value: 0.79Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: Day 5 and Day 15
Population: Those who completed Day 15
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Blinded Intervention Group | Index of Nausea, Vomiting and Retching: Total Experience Score | -2.3 score on a scale |
| Blinded Placebo Group | Index of Nausea, Vomiting and Retching: Total Experience Score | -2.5 score on a scale |
p-value: 0.57Wilcoxon (Mann-Whitney)