Oral Akynzeo® vs Standard of Care in Preventing CINV in High-risk MEC Patients (MyRisk)

NCT ID: NCT04817189

Last Updated: 2025-12-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 414 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-01
• Study Completion Date: 2024-07-02

Brief Summary

MyRisk: Efficacy and safety evaluation of oral Akynzeo® in patients receiving MEC at high risk of developing CINV based on a prediction tool. A multinational and multicenter study.

Antiemetic guidelines recommendations are based on the emetogenic potential of the chemotherapy. Chemotherapy (CT) agents are divided in Highly, Moderately, Low and Minimally Emetogenic potential.

In addition to type of chemotherapy, several patient-related risk factors can increase the risk of CINV (chemotherapy-induced nausea and vomiting). Currently, there is limited consensus surrounding the most relevant patient risk factors that may predict the risk of CINV. Based on a recent study by Dranitsaris et al. (Dranitsaris et al. Ann Oncol. 2017 Jun 1; 28(6):1260-1267.), eight (8) predictive factors have been identified and an algorithm has been developed to incorporate these factors into the optimal selection of prophylactic antiemetics:

1. nausea and/or vomiting in the prior cycle of chemotherapy

2. use of non-prescribed antiemetics at home in the prior cycle of chemotherapy

3. platinum or anthracycline-based chemotherapy

4. age < 60 years

5. expectations for (anticipating) nausea and/or vomiting

6. <7 h of sleep the night before chemotherapy

7. history of morning sickness during previous pregnancy

8. cycle of chemotherapy (A negative association between risk and number of cycles was identified where the hazard for CINV was highest in cycles 1 and 2, with a gradual decline and plateau from cycle 3 onward).

The clinical application of this prediction tool has the potential to be an important resource for clinicians and may help to enhance patient care by optimizing the use of the antiemetics in a proactive manner.

Detailed Description

Antiemetic guideline recommendations are based on the emetogenic potential of chemotherapy and involve 4 levels of classification of intravenous chemotherapy agents, i.e., high, moderate, low and minimal; these have been accepted by major organisations. Moderate emetogenic chemotherapy (MEC) results in acute vomiting in 30% to 90% of cancer patients in the absence of antiemetic therapy. In addition to the chemotherapy type, several patient-related risk factors and clinical characteristics can increase CINV risk. These can include use of antiemetics inconsistent with international guidelines, younger age, prechemotherapy nausea, no complete CINV response in an earlier cycle, history of nausea/vomiting, (trait) anxiety, fatigue experience, and expectations of nausea/vomiting. Other studies have largely confirmed some of the key risk factors for CINV (history of vomiting during pregnancy, history of motion sickness, age, gender) and added other factors such as (chronic) alcohol consumption, body surface area, fewer hours slept the night prior to infusion, or advanced stage cancer. Currently, there is a limited consensus surrounding the most relevant patient risk factors that may predict CINV risk. Based on a recent study by Dranitsaris et al. eight predictive factors have been identified, and an algorithm has been developed to combine these patient-related risk factors into the optimal treatment of prophylactic antiemetics. These include:

1. nausea and/or vomiting in the prior cycle of chemotherapy

2. use of non-prescribed antiemetics at home in the prior cycle of chemotherapy

3. platinum or anthracycline-based chemotherapy

4. age < 60 years

5. expectations for (anticipating) nausea and/or vomiting

6. <7 h of sleep the night before chemotherapy

7. history of morning sickness during previous pregnancy

8. cycle of chemotherapy (A negative association between risk and number of cycles was identified where the hazard for CINV was highest in cycles 1 and 2, with a gradual decline and plateau from cycle 3 onward).

Akynzeo®, an oral combination of the neurokinin 1 receptor antagonists (NK1 RA), netupitant and the 5-hydroxytryptamine (HT3) receptor antagonists (5-HT3 RA), palonosetron, is recommended by guidelines for the prevention of CINV. Akynzeo® has been evaluated in a multicentre, randomised, double-blind, double-dummy phase II clinical trial at various dose ranges among 694 cisplatin-treated cancer patients from 44 sites (two countries); each NEPA (netupitant-palonosetron) dose significantly improves CINV prevention in cancer patients. Similar results were obtained in another international, randomised, double-blind and parallel group phase III clinical trial; NEPA prevented CINV in patients receiving MEC.

The current study primarily aimed to evaluate whether Akynzeo® leads to a higher response rate compared with standard care in MEC regimen-treated patients who are identified to be at high risk based on the algorithm.

Conditions

Chemotherapy-induced Nausea and Vomiting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg

Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle.

Dexamethasone (8 mg) will be administered on Day 1 of each cycle.

Group Type: EXPERIMENTAL

Dexamethasone, 8 mg (oral) or equivalent IV dose

Intervention Type: DRUG

Dexamethasone (8 mg) will be administered on Day 1 of each cycle.

NEPA (300mg netupitant/0.5mg palonosetron)

Intervention Type: DRUG

Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle.

Standard of care + Dexamethasone 8 mg

Dexamethasone (or equivalent corticosteroids) 8 mg administered by the oral route (or equivalent IV dose) on Day 1, approximately 1 hour before chemotherapy and one of the 5-HT3-RAs recommended by European Society for Medical Oncology (ESMO) and Multinational Association of Supportive Care in Cancer (MASCC) guidelines (standard of care), i.e. either:

Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)

Group Type: ACTIVE_COMPARATOR

Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)

Intervention Type: DRUG

Standard of care will be administered on Day 1 of each cycle.

Dexamethasone, 8 mg (oral) or equivalent IV dose

Intervention Type: DRUG

Dexamethasone (8 mg) will be administered on Day 1 of each cycle.

Interventions

Granisetron, 2 mg (oral) or 1 mg (IV) OR Palonosetron, 0.5 mg (oral), 0.25mg (IV) OR Ondansetron, 16 mg (oral) or 8 mg (IV) OR Dolasetron 100 mg (oral) OR Tropisetron 5 mg (oral or IV)

Standard of care will be administered on Day 1 of each cycle.

Intervention Type: DRUG

Dexamethasone, 8 mg (oral) or equivalent IV dose

Dexamethasone (8 mg) will be administered on Day 1 of each cycle.

Intervention Type: DRUG

NEPA (300mg netupitant/0.5mg palonosetron)

Oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle.

Intervention Type: DRUG

Other Intervention Names

Akynzeo® capsules; 5-HT3 RA; corticosteroid

Eligibility Criteria

Inclusion Criteria

• Adult patients aged ≥18 years
• Patients with a risk score of ≥ 13 as calculated by the algorithm - see 3.6.3.1. Baseline/screening: VISIT 0
• Signed Informed consent
• Both sexes
• Patients with diagnosis of any cancer scheduled and intended to be treated for three consecutive cycles with a single dose of any IV MEC regimen, per cycle, including adjuvant or neo-adjuvant chemotherapy
• Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• Use of Standard of Care defined as a 5-HT3 RA + Dexamethasone (or equivalent corticosteroid) based-regimen on day 1 of chemotherapy for CINV prevention
• Naïve and non- naïve to chemotherapy
• The enrolled women should be a) of non-childbearing potential or b) of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test done by health care team within 1-24 hours before dosing the antiemetic treatment in both arms and outcome recorded in the medical records
• Able to comply with study requirements

Exclusion Criteria

• Patients receiving highly emetogenic chemotherapy (including anthracycline+cyclophosphamide-based chemotherapy)
• Patients receiving oral moderately emetogenic chemotherapy drugs
• Patients receiving opioids within 2 weeks prior to trial enrollment (longer use allowed)
• Use of olanzapine as prophylaxis of CINV
• Patients scheduled to receive radiotherapy concurrently with chemotherapy
• Any illness or condition that, in the opinion of the physician, may confound the results of the study or pose unwarranted risks in administering the investigational product to the patient.
• Patients with mechanical risk factors for nausea (i.e. intestinal obstruction)
• Patients with liver disease (as nausea is a common presenting symptom)
• Patients with metabolic risk factors for nausea (i.e. electrolyte imbalances causing nausea/vomiting)
• Chronic treatment with steroids (with the exception of inhaled or topical steroids)
• Pregnancy and/or breast-feeding women
• Women of childbearing potential refusing to use effective contraception during the whole study treatment and up to one month after study treatment with Akynzeo®
• Use of Standard of Care including an NK-1 RA-based regimen to prevent CINV

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Helsinn Healthcare SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alex Molasiotis, prof.

Role: STUDY_CHAIR

University of Derby

Locations

Shanghai Chest Hospital

Shanghai, , China

Shanghai Ninth People´s Hospital

Shanghai, , China

Shanghai Obstetrics and Gynecology Hospital

Shanghai, , China

Thomayerova nemocnice

Prague, , Czechia

General University Hospital in Prague

Prague, , Czechia

Evang. Kliniken Essen-Mitte

Essen, , Germany

Universitätsmedizin Mannheim

Mannheim, , Germany

München Klinik Neuperlach

München, , Germany

Frauenklinik St. Louise

Paderborn, , Germany

Klinikum Ernst von Bergmann gemeinnützige GmbH

Potsdam, , Germany

Sotiria General Hospital, 3rd Deúpartment of Medicine, School of Medicine, National and Kapodistrian University of Athens

Athens, , Greece

General University Hospital of Heraklion

Heraklion, , Greece

Complejo Hospitalario Universitario de A Coruña

A Coruña, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

University Hospital Basel

Basel, , Switzerland

Swiss Medical Network - Clinique de Genolier

Genolier, , Switzerland

The Royal Marsden Hospital

London, , United Kingdom

Countries

China; Czechia; Germany; Greece; Spain; Switzerland; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

IBA1160

Identifier Type: -

Identifier Source: org_study_id