Symptoms and General Pathology

All Conditions

Rare Diseases

Nausea

Vomiting

Signs and Symptoms, Digestive

Chronic Graft Versus Host Disease

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Palonosetron

Serotonin

Serotonin 5-HT3 Receptor Antagonists

Neurotransmitter Agents

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.

Netupitant

Palonosetron Hydrochloride

Placebo

Questionnaire Administration

David Hui

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.

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.

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

Fixed-Dose Netupitant and Palonosetron for Chronic Nausea and Vomiting in Cancer Patients

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.

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.

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, 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.

National Cancer Institute (NCI)

Helsinn Healthcare SA

M.D. Anderson Cancer Center

Adverse events were assessed within 15 study days

Took one Netupitant/Palonosetron (NEPA) capsule every 5 days for 2 doses

Blinded Intervention gp.

Took one Placebo capsule every 5 days for 2 doses

Placebo gp.

Took Placebo capsule every 5 days for 2 doses

Blinded Placebo gp.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Cancer Stage

Cancer Type

We have 2 arms in this study (intervention group and Placebo group) during randomization. These 2 arms included all participants who entered in Placebo run out phase. Baseline characteristics thus have 2 arms/groups.

Dr. David Hui

Netupitant/Palonosetron (NEPA) capsule every 5 days for 2 doses

Blinded Intervention Group

Blinded Placebo Group

Change in Nausea Numerical Rating Scale (NRS) Between Day 5 and Day 15

Blinded Intervention Group.

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

Functional Living Index Emesis (FLIE): Vomiting Sub-score

Index of Nausea, Vomiting and Retching: Total Experience Score

Overall Study

Within 60 minutes before standard of care BEAM treatment, patients receive netupitant and palonosetron hydrochloride PO on days 1, 3, and 6.

Netupitant: 300 mg, QD, Given PO Palonosetron Hydrochloride: 0.5 mg, QD, Given PO Questionnaire Administration: Ancillary studies

Joseph Bubalo

This phase II trial studies how well netupitant and palonosetron hydrochloride work in preventing chemotherapy induced nausea and vomiting in patients with cancer undergoing BEAM conditioning regimen before stem cell transplant. Chemotherapy, such as carmustine, cytarabine, etoposide, and melphalan (BEAM), makes people feel sick to their stomach and causes vomiting. Netupitant and palonosetron hydrochloride may reduce the nausea and vomiting caused by the BEAM treatment.

PRIMARY OBJECTIVES:

I. To assess the efficacy of netupitant and palonosetron hydrochloride (NEPA) to prevent nausea and vomiting both during and after a highly emetogenic (BEAM) conditioning regimen for hematopoietic stem cell transplantation (HSCT).

SECONDARY OBJECTIVES:

I. To differentiate response to NEPA over different phases of chemotherapy-induced nausea.

OUTLINE:

Within 60 minutes before standard of care BEAM treatment, patients receive netupitant and palonosetron hydrochloride orally (PO) on days 1, 3, and 6.

After completion of study treatment, patients are followed up at 14 days.

Netupitant and Palonosetron Hydrochloride in Preventing Chemotherapy Induced Nausea and Vomiting in Patients With Cancer Undergoing BEAM Conditioning Regimen Before Stem Cell Transplant

A Phase II Clinical Trial of NEPA (Netupitant/Palonosetron) for Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) in Patient Receiving the BEAM Conditioning Regimen Prior to Hematopoietic Cell Transplantation (HSCT)

The number of participants that had emetic episodes and received rescue agents (medications).

The number of participants that had emetic episodes and received rescue agents (medications) (acute phase: for 0 to 144 hours timeframe of study drug administration)

The number of participants that had emetic episodes and received rescue agents (medications) (for 0 to 24 hours timeframe of study drug administration)

The number of participants that had emetic episodes and received rescue agents (medications) during the delayed phase (for 145 hours up to 264 hours timeframe)

The mean level of nausea per day assessed by chemotherapy induced nausea and vomiting questionnaire. The full range of nausea level score on the questionnaire was from minimum value of 0 to a maximum value of 10. 0= no nausea or vomiting, and 10= worst nausea and vomiting. Higher score means a worse outcome.

Will be depicted via Kaplan-Meier curves showing the percentage of patients who had no emesis or rescue medication use for the acute and delayed time periods.

Number of subjects that reached a complete response (CR), defined as having no emesis and no rescue therapy.

Number of subjects that reached a complete response (CR), defined as having no emesis and no rescue therapy from 0 to 144 hours (acute phase) of the study drug administration.

Number of subjects that reached a complete response (CR), defined as having no emesis and no rescue therapy from 145 hours up to 264 hours (delayed phase) of the study drug administration.

Number of subjects that reached a complete response (CR), defined as having no emesis and no rescue therapy from 0 to 264 hours of the study drug administration.

Helsinn Therapeutics (U.S.), Inc

Oregon Health and Science University

OHSU Knight Cancer Institute

Principal Investigator

Supportive Care (NEPA)

Race

Race/Ethnicity, Customized

Joseph Bubalo, PharmD (Oncology Clinical Pharmacy Specialist)

Complete Response (CR) Defined as no Emesis and no Rescue Therapy

CR (Acute Phase)

CR (Delayed Phase)

42 participants completed the study and therefore were analyzed for response.

Complete Protection (CP) Rate Defined as CR Plus no Nausea

Number of participants who had emetic episodes

Number of participants who were given rescue meds

Number of Participants With Emetic Episodes and Received Rescue Agents

Number of participants who had an emetic episode in acute phase

Number of participants who were given rescue meds in acute phase

Number of Participants With Emetic Episodes and Received Rescue Agents (Acute Phase)

Number of participants that had emetic episodes

Number of participants that were given rescue meds-

The number of participants that had an emetic episode

The number of participants that were given rescue meds

Number of Participants With Emetic Episodes and Received Rescue Agents (Delayed Phase)

Mean Levels of Nausea Per Day Assessed by Chemotherapy Induced Nausea and Vomiting Questionnaire

Median time to receiving rescue medication

Time to first emesis

Time to First Emesis and Time to Receiving First Rescue Medication

Mean time to first rescue medication

Mean time to first emesis

Time to Receiving First Rescue Medication and First Emesis

Within 60 minutes before standard of care BEAM treatment, patients receive netupitant and palonosetron hydrochloride PO on days 1, 3, and 6.

Netupitant: 300 mg, QD, Given PO

Palonosetron Hydrochloride: 0.5 mg, QD, Given PO

Questionnaire Administration: Ancillary studies

Pharmaceutical Solutions

Emetics

Single oral dose of Netupitant 1.33 mg/kg up to a maximum of 100 mg (for patients \< 3 months of age the netupitant dose will be 0.8 mg/kg) administered with single oral dose of 20 μg/kg palonosetron up to a maximum of 1.5 mg.

Single oral dose of Netupitant 4 mg/kg up to a maximum of 300 mg (for patients \< 3 months of age the netupitant dose will be 2.4 mg/kg) administered with single oral dose 20 μg/kg palonosetron up to a maximum of 1.5 mg.

Netupitant 1.33 mg/kg oral suspension up to a maximum of 100 mg

Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg

Netupitant 4 mg/kg oral suspension up to a maximum of 300 mg

This study is Phase 2 pharmacokinetic (PK) and pharmacodynamic (PD) dose-finding study of oral netupitant administered concomitantly with oral palonosetron in pediatric cancer patients for the prevention of nausea and vomiting associated with emetogenic chemotherapy. Two different netupitant dosages will be tested in patients aged from 3 months to \< 18 years: 1.33 mg/kg up to a maximum of 100 mg, and 4 mg/kg up to a maximum of 300 mg. All netupitant doses in all age classes will be concomitantly administered with palonosetron 20 μg/kg (up to a maximum dose of 1.5 mg) which is the IV palonosetron dose approved by USA FDA for the pediatric population. The primary objective is to investigate the PK/PD relationship between netupitant exposure (AUC, Cmax) and antiemetic efficacy (CR in delayed phase) after a single oral netupitant administration, concomitantly with oral palonosetron in pediatric cancer patients receiving Moderately Emetogenic Chemotherapy (MEC) or Highly Emetogenic Chemotherapy (HEC) cycles. Efficacy parameter to be used in the correlation is the proportion of patients with Complete Response (CR i.e., no emetic episodes and no rescue medication) during (\> 24-120 h after the start of chemotherapy on Day 1).

The secondary objectives are to assess the safety and tolerability after single oral administration of netupitant given concomitantly with a single oral administration of palonosetron; to evaluate the pharmacokinetic (AUC, Cmax, tmax and t1/2) of oral palonosetron at the fixed dose of 20 μg/kg in pediatric patients with the concomitant administration of netupitant. A total of 92 pediatric cancer patients receiving either HEC or MEC will be enrolled in the study.

PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea and Vomiting

A Multicenter Multinational Randomized Double Blind PK/PD Dose-finding Study of Oral Netupitant Given With Oral Palonosetron in Pediatric Cancer Patients for Prevention of Nausea and Vomiting Associated With Emetogenic Chemotherapy

Mean values of area under the plasma Concentration versus time curve from time zero to infinity (AUC0-inf) of netupitant after a single oral netupitant administration, concomitantly with oral palonosetron, in pediatric cancer patients receiving HEC or MEC cycles. AUC estimates are obtained by non-compartmental analysis of population model-predicted individual plasma concentration-time profiles.

Mean values of maximum plasma concentration (Cmax) of netupitant after a single oral netupitant administration, concomitantly with oral palonosetron, in pediatric cancer patients receiving HEC or MEC cycles. Cmax estimates are obtained by non-compartmental analysis of population model-predicted individual plasma concentration-time profiles

Exposure - Response analysis for netupitant performed by assessing the relationships between exposure parameters AUC0-inf and Cmax with the primary efficacy endpoint, i.e., the CR in the delayed phase.

Graphical exposure-response analysis for netupitant performed by assessing the relationship between individual exposure parameters (AUC0-inf) and Cmax) with the primary efficacy endpoint, i.e the CR in the delayed phase.

Percentage of Pediatric Patients with complete response (CR, i.e., no emetic episodes and no rescue medication) during the delayed phase (\> 24 to 120 h after the start of chemotherapy on Day 1) after a single oral netupitant administration, concomitantly with oral palonosetron, in pediatric cancer patients receiving HEC or MEC cycles.

Single oral dose of Netupitant 1.33 mg/kg up to a maximum of 100 mg (for patients \< 3 months of age the netupitant dose will be 0.8 mg/kg) administered with single oral dose of 20 μg/kg palonosetron up to a maximum of 1.5 mg.

Netupitant: Netupitant 1.33 mg/kg oral suspension up to a maximum of 100 mg

Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg

Netupitant 1.33 mg/kg Plus Palonosetron

Single oral dose of Netupitant 4 mg/kg up to a maximum of 300 mg (for patients \< 3 months of age the netupitant dose will be 2.4 mg/kg) administered with single oral dose 20 μg/kg palonosetron up to a maximum of 1.5 mg.

Netupitant: Netupitant 4 mg/kg oral suspension up to a maximum of 300 mg

Palonosetron: Palonosetron 20 μg/kg solution for oral use up to a maximum of 1.5 mg

Netupitant 4 mg/kg Plus Palonosetron

Age, Customized

Male and female pediatric cancer patients from birth up to \<18 years, who were scheduled to receive HEC or MEC to be administered as single-day chemotherapy on Day 1 only or for multiple days. All participants who received study drug. In netupitant 4 mg/kg arm 1 patient was withdrew from the study after randomization of study drug and was not treated with the study drug (the overall number of participants started in netupitant 4 mg/kg arm was 33 and 32 patients completed the study).

Edwin de Wit - Head of Clinical Development

patients 1 month to <3 months of age

patients 3 month to <6 months of age

patients 6 month to <1 year of age

patients 1 year to <2 years

patients 2 years to <5 years

patients 5 years to <12 years

patients 12 years to <18 years

Pediatric patients divided in seven age groups; in netupitant 4 mg/kg arm 1 patient was withdrew from the study after randomization of study drug and was not treated; 1 patient was treated with study drug but did not receive the entire planned dose and was not included in this analysis and one patient received the entire planned dose, but did not have any measurable concentration of netupitant and/or palonosetron.

Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Netupitant

1 month to <3 months

3 months to <6 months

6 months to <12 months

1 year to <2 years

2 years to <5 years

5 years to <12 years

12 years to <18 years

Maximum Plasma Concentration (Cmax) of Netupitant

The population consist of all patients having CR in the delayed phase and AUC0-inf and Cmax, there is no comparison between the two dose groups.

Single oral dose of Netupitant 1.33 mg/kg up to a maximum of 100 mg (for patients \< 3 months of age the netupitant dose will be 0.8 mg/kg) administered with single oral dose of 20 μg/kg palonosetron up to a maximum of 1.5 mg.

Or Single oral dose of Netupitant 4 mg/kg up to a maximum of 300 mg (for patients \< 3 months of age the netupitant dose will be 2.4 mg/kg) administered with single oral dose 20 μg/kg palonosetron up to a maximum of 1.5 mg.

Netupitant 1.33 mg/kg Plus Palonosetron or Netupitant 4 mg/kg Plus Palonosetron

All pediatric patients with exposures parameters and CR data in the delayed phase

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Netupitant and Palonosetron Hydrochloride in Preventing Chronic Nausea and Vomiting in Patients With Cancer	NCT03040726	Malignant Neopl... Nausea Vomiting	Netupitant Palonosetron Palonosetron Hy... Placebo Questionnaire A...	18 Years -	M.D. Anderson Cancer Center
Netupitant and Palonosetron Hydrochloride in Preventing Chemotherapy Induced Nausea and Vomiting in Patients With Cancer Undergoing BEAM Conditioning Regimen Before Stem Cell Transplant	NCT03097588	Malignant Neopl...	Netupitant Palonosetron Hy... Questionnaire A...	18 Years -	OHSU Knight Cancer Institute
PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea and Vomiting	NCT03204279	Chemotherapy-in...	Netupitant Palonosetron Netupitant Palonosetron	- 17 Years	Helsinn Healthcare SA

Spots Global Cancer Trial Database for netupitant

Every month we try and update this database with for netupitant cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for netupitant

Every month we try and update this database with for netupitant cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for netupitant cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.