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

Malignant Neoplasm Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03097588
• Other study ID #: STUDY00016288
• Secondary ID: NCI-2017-00548ST
• Status: Completed
• Phase: Phase 2
• Start date: April 27, 2017
• Est. completion date: March 20, 2020

Study information

• Verified date: June 2021
• Source: OHSU Knight Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: March 20, 2020
• Est. primary completion date: February 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects must be undergoing autologous or allogeneic hematopoietic stem cell transplant (HSCT) with the BEAM conditioning regimen prior to HSCT

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 or Karnofsky Performance Score >= 60%

• Able to swallow oral medications

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Subjects with known hypersensitivity or other allergic reactions attributed to compounds of similar biologic composition to netupitant, palonosetron, dexamethasone, or other agents used in the study

• Subjects who are receiving any other investigational agents or have received another investigational drug in the last 30 days

• Subjects who have had emesis or required antiemetics in the 48 hours prior to starting the BEAM conditioning regimen; patients required to take antipsychotics, appetite stimulants, or other medications with antiemetic effects will also be excluded if those medications cannot be replaced by therapeutic equivalents

• Female subjects who are pregnant, have a positive serum human chorionic gonadotrophin (hCG), or are lactating and intend to breastfeed a child; pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with NEPA

• Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy are ineligible

• Subjects who have taken a neurokinin antagonist within 14 days prior to beginning the BEAM regimen

• Subjects who have a serum creatinine > 2 x upper limit of normal (ULN)

• Subjects with severe renal failure or end stage renal disease (estimated GFR [glomerular filtration rate] of < 30 mL/min) as estimated by the Cockcroft-Gault formula

• Subjects with severe hepatic insufficiency (Child Pugh score > 9)

• Subjects who have been reported > 5 alcoholic drinks daily for the last year

• Subjects who have concurrent illness requiring systemic corticosteroid use other than the planned dexamethasone during conditioning therapy

• Subjects with gastrointestinal conditions that might result in malabsorption of the study drug

• Subjects with a history of anxiety-induced ("anticipatory") nausea and vomiting

• Subjects on strong CYP 3A4 inducers or inhibitors who are unable to have those agents replaced with clinical alternatives prior to beginning the study; length of washout period will be 7 days; notably, in the case of allogeneic transplant recipients requiring cyclosporine or tacrolimus, no empiric dose adjustments will be required due to close level monitoring and adjustments, that are standard in Oregon Health & Science University (OHSU) protocols

• Subjects unable to discontinue benzodiazepines as antiemetics will not be allowed; additional antiemetics will be allowed for rescue but not for prophylaxis

• Subjects with personal or family history of QT prolongation, uncorrected electrolyte abnormalities, congestive heart failure, bradyarrhythmia, conduction disturbances and those taking antiarrhythmic medicinal products or other medicinal products that lead to QT prolongation or electrolyte abnormalities; relevant information will be collected as part of subject medical history

Related Conditions & MeSH terms

• Malignant Neoplasm
• Neoplasms
• Vomiting

Intervention

Drug:
• Netupitant
300 mg, Given PO, QD
• Palonosetron Hydrochloride
0.5 mg, Given PO, QD

Other:
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
United States	OHSU Knight Cancer Institute	Portland	Oregon

Sponsors (3)

Lead Sponsor	Collaborator
OHSU Knight Cancer Institute	Helsinn Therapeutics (U.S.), Inc, Oregon Health and Science University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Emetic Episodes and Received Rescue Agents	The number of participants that had emetic episodes and received rescue agents (medications).	Up to 264 hours
Other	Number of Participants With Emetic Episodes and Received Rescue Agents (Acute Phase)	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)	Up to 144 hours post-study drug administration on day 1
Other	Number of Participants With Emetic Episodes and Received Rescue Agents (Acute Phase)	The number of participants that had emetic episodes and received rescue agents (medications) (for 0 to 24 hours timeframe of study drug administration)	Up to 24 hours post-study drug administration on day 1
Other	Number of Participants With Emetic Episodes and Received Rescue Agents (Delayed Phase)	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)	From 145 hours up to 264 hours post-study drug administration on day 1
Other	Mean Levels of Nausea Per Day Assessed by Chemotherapy Induced Nausea and Vomiting Questionnaire	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.	Up to 11 days
Other	Time to First Emesis and Time to Receiving First Rescue Medication	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.	Up to 264 hours
Other	Time to Receiving First Rescue Medication and First Emesis	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.	Up to 264 hours
Primary	Complete Response (CR) Defined as no Emesis and no Rescue Therapy	Number of subjects that reached a complete response (CR), defined as having no emesis and no rescue therapy.	Up to 5 days post chemotherapy
Secondary	CR (Acute Phase)	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.	Up to 144 hours post-study drug administration on day 1
Secondary	CR (Delayed Phase)	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.	From 145 hours up to 264 hours post-study drug administration on day 1
Secondary	Complete Protection (CP) Rate Defined as CR Plus no Nausea	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.	Up to 264 hours post-study drug administration on day 1