Clinical trial NCT04817189: Oral Akynzeo® Vs Standard of Care in Preventing CINV in High-risk MEC Patients (MyRisk)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chemotherapy-induced Nausea and Vomiting
Lead sponsor: Helsinn Healthcare SA
Sponsor class: INDUSTRY
First posted: 2021-03-26
Enrollment: 414
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: interventional, open label, randomized, active controlled, parallel arms, multicenter and multinational study
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: The proportion of complete responses over three cycles of chemotherapy after the start of the MEC administration
timeFrame: 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:
measure: Evaluation of acute (0 to 24 hours), delayed (>24 to 120 hours), and overall (0-120 hours) CINV indicators in each cycle of chemotherapy
timeFrame: 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).
measure: Evaluation of the predictive role of potential risk factors in the development of CINV over three cycles of chemotherapy
timeFrame: 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).
measure: Evaluation of the safety profile of the antiemetic drug over three cycles of chemotherapy - the frequency of adverse events (AE)
timeFrame: 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).
measure: Evaluation of the safety profile of the antiemetic drug over three cycles of chemotherapy - the percentage of adverse events (AE)
timeFrame: 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).
measure: Evaluation of the frequency of discontinuations due to adverse events
timeFrame: 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).
measure: Evaluation of the percentage of discontinuations due to adverse events
timeFrame: 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).
measure: Evaluation of frequency of on treatment deaths due to adverse events
timeFrame: 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).
measure: Evaluation of the percentage of patients with on treatment death due to adverse events
timeFrame: 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).
measure: Listings concerning the safety profile of the antiemetic drug over three cycles of chemotherapy
timeFrame: 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).
measure: Exploration of the effect of CINV on daily activities and quality of life in patients receiving moderately-emetogenic chemotherapy over three cycles of chemotherapy
timeFrame: 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).
measure: Evaluation of resource utilization and health economic outcome - number of days with rescue medication administered for the treatment of CINV
timeFrame: 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).
measure: Evaluation of resource utilization and health economic outcome - daily doses of rescue medication administered for the treatment of CINV
timeFrame: 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).
measure: Evaluation of resource utilization and health economic outcome - the number of re-hydration bags
timeFrame: 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).
measure: Evaluation of resource utilization and health economic outcome - the number of days of unplanned hospitalisations
timeFrame: 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).
measure: Evaluation of resource utilization and health economic outcome - the number of outpatient physician visits
timeFrame: 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).
measure: Evaluation of resource utilization and health economic outcome - the number of unplanned laboratory test
timeFrame: 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).
measure: Evaluation of resource utilization and health economic outcome - discontinuation of chemotherapy treatment due to CINV
timeFrame: 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).
measure: Evaluation of resource utilization and health economic outcome - the number of delays of chemotherapy administration due to CINV
timeFrame: 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).
measure: Evaluation of resource utilization and health economic outcome - the average length of delay of chemotherapy administration due to CINV
timeFrame: 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).
measure: Evaluation of resource utilization and health economic outcome - days of absence from work
timeFrame: 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).
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Chest Hospital
city: Shanghai
country: China
facility: Shanghai Ninth People´s Hospital
city: Shanghai
country: China
facility: Shanghai Obstetrics and Gynecology Hospital
city: Prague
country: Czechia
facility: General University Hospital in Prague
city: Praha
country: Czechia
facility: Thomayerova nemocnice
city: Essen
country: Germany
facility: Evang. Kliniken Essen-Mitte
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim
city: München
country: Germany
facility: München Klinik Neuperlach
city: Paderborn
country: Germany
facility: Frauenklinik St. Louise
city: Potsdam
country: Germany
facility: Klinikum Ernst von Bergmann gemeinnützige GmbH
city: Athens
country: Greece
facility: Sotiria General Hospital, 3rd Deúpartment of Medicine, School of Medicine, National and Kapodistrian University of Athens
city: Heraklion
country: Greece
facility: General University Hospital of Heraklion
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario de A Coruña
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Genolier
country: Switzerland
facility: Swiss Medical Network - Clinique de Genolier
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
Study officials:
affiliation: University of Derby
name: Alex Molasiotis, prof.
role: STUDY_CHAIR
References: