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

NCT04817189 | Completed Phase 4 Results

• 1 other identifier: IBA1160
• Study Type: interventional
• Target: 414
• Locations: 7 countries
• Sites: 19

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. 1.nausea and/or vomiting in the prior cycle of chemotherapy
2. 2.use of non-prescribed antiemetics at home in the prior cycle of chemotherapy
3. 3.platinum or anthracycline-based chemotherapy
4. 4.age \< 60 years
5. 5.expectations for (anticipating) nausea and/or vomiting
6. 6.\<7 h of sleep the night before chemotherapy
7. 7.history of morning sickness during previous pregnancy
8. 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).

Conditions

Chemotherapy-induced Nausea and Vomiting

Outcome Measures

Primary Outcomes (1)

• The Probability of Complete Responses Over Three Cycles of Chemotherapy After the Start of the MEC Administration

  To evaluate if the use of NEPA (netupitant and palonosetron) in patients treated with IV moderately emetogenic chemotherapy and at high risk of CINV is more effective in preventing CINV than a standard of care antiemetics over three cycles of chemotherapy. The primary endpoint is the probability of complete responses (no emetic episode and no rescue medication), during the overall phase (0-120h), after the start of the MEC administration over three cycles of chemotherapy. This endpoint is evaluated in patients with at least one reported cycle assessment. The model-based statistics of generalized linear model were used to calculate the difference in the probability to experience a "per cycle" CINV Indicators between the treatment arms.

  At the end of all three chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

Secondary Outcomes (20)

• Evaluation of the Probability of Acute (0 to 24 Hours), Delayed (>24 to 120 Hours), and Overall (0-120 Hours) CINV Indicators in Each Cycle of Chemotherapy

  At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

• Evaluation of the Predictive Role of Potential Risk Factors in the Development of CINV Over Three Cycles of Chemotherapy

  At the end of each cycle and after all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

• Evaluation of the Safety Profile of the Antiemetic Drug Over Three Cycles of Chemotherapy - the Frequency of Adverse Events (AE)

  At the end of all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

• Evaluation of the Safety Profile of the Antiemetic Drug Over Three Cycles of Chemotherapy - Percentage of Participants With Adverse Events

  At the end of all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

• Number of Participants With Discontinuations Due to Adverse Events

  At the end of all 3 chemotherapy cycles. The length of a cycle depends on the treatment being given (cycles range from 2 to 6 weeks).

Study Arms (2)

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

EXPERIMENTAL

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.

Drug: NEPA (300mg netupitant/0.5mg palonosetron); Drug: Dexamethasone, 8 mg (oral) or equivalent IV dose

Standard of care + Dexamethasone 8 mg

ACTIVE COMPARATOR

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)

Drug: 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); Drug: Dexamethasone, 8 mg (oral) or equivalent IV dose

Interventions

NEPA (300mg netupitant/0.5mg palonosetron) DRUG

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

Also known as: Akynzeo® capsules

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

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) DRUG

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

Also known as: 5-HT3 RA

Standard of care + Dexamethasone 8 mg

Dexamethasone, 8 mg (oral) or equivalent IV dose DRUG

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

Also known as: corticosteroid

NEPA (300mg netupitant/0.5mg palonosetron) + Dexamethasone 8 mg; Standard of care + Dexamethasone 8 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Helsinn Healthcare SA: lead

Study Sites (19)

Shanghai Chest Hospital

Shanghai, China

Location

Shanghai Ninth People´s Hospital

Shanghai, China

Location

Shanghai Obstetrics and Gynecology Hospital

Shanghai, China

Location

Thomayerova nemocnice

Prague, 14059, Czechia

Location

General University Hospital in Prague

Prague, Czechia

Location

Evang. Kliniken Essen-Mitte

Essen, Germany

Location

Universitätsmedizin Mannheim

Mannheim, Germany

Location

München Klinik Neuperlach

München, Germany

Location

Frauenklinik St. Louise

Paderborn, Germany

Location

Klinikum Ernst von Bergmann gemeinnützige GmbH

Potsdam, Germany

Location

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

Athens, Greece

Location

General University Hospital of Heraklion

Heraklion, Greece

Location

Complejo Hospitalario Universitario de A Coruña

A Coruña, 15006, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 0802, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

University Hospital Basel

Basel, Switzerland

Location

Swiss Medical Network - Clinique de Genolier

Genolier, Switzerland

Location

The Royal Marsden Hospital

London, United Kingdom

Location

MeSH Terms

Conditions

Vomiting

Interventions

netupitant, palosentron drug combination; Granisetron; Palonosetron; Ondansetron; dolasetron; Tropisetron; Dexamethasone; Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinuclidines; Isoquinolines; Imidazoles; Carbazoles; Indoles; Heterocyclic Compounds, 3-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Alessandro Alonzi, Medical Advisor
• Organization: Helsinn

Alessandro.Alonzi@helsinn.com

+41793262091

Study Officials

• Alex Molasiotis, prof.

  University of Derby

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: interventional, open label, randomized, active controlled, parallel arms, multicenter and multinational study

Study Record Dates

• First Submitted: March 1, 2021
• First Posted: March 26, 2021
• Study Start: February 1, 2021
• Primary Completion: July 2, 2024
• Study Completion: July 2, 2024
• Last Updated: December 2, 2025
• Results First Posted: October 29, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4); GB (1); GR (2); CH (2); CZ (2); CN (3); DE (5)