E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients treated with IV moderately emetogenic chemotherapy and at high risk of chemotherapy induced nausea and vomiting (CINV) |
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E.1.1.1 | Medical condition in easily understood language |
Patients treated with chemotherapy and at high risk of chemotherapy induced nausea and vomiting (CINV) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate if the use of Akynzeo® (a fixed oral dose combination of the NK1-RA netupitant 300 mg and 5-HT3-RA palonosetron 0.5 mg) in patients treated with intra-venous moderately emetogenic chemotherapy and at high risk of chemotherapy induced nausea and vomiting (CINV) is more effective in preventing CINV than standard of care antiemetics over three cycles of chemotherapy.
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E.2.2 | Secondary objectives of the trial |
Evaluate acute, delayed, and overall CINV indicators in each cycle of chemotherapy
Evaluate the predictive role of potential risk factors in the development of CINV over three cycles of chemotherapy
Evaluate the safety profile of the antiemetic drug over three cycles of chemotherapy
Explore the effect of CINV on daily activities and quality of life in patients receiving moderately-emetogenic chemotherapy over three cycles of chemotherapy
Evaluate resource utilization and health economic outcome |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 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 |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the proportion of complete responses (no emetic episode and no rescue medication) over three cycles of chemotherapy after the start of the MEC administration. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Measured at patients last visit following 3 chemotherapy cycles |
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E.5.2 | Secondary end point(s) |
• No emetic episode during the acute, delayed and overall phase and daily in each cycle; • Number of vomiting episodes during the acute, delayed and overall phase in each cycle; • No rescue medication during the acute, delayed and overall phase and daily in each cycle; • No significant nausea (maximum MAT scale= 2) during the acute, delayed and overall phase and daily in each cycle; • No nausea (MAT scale = 0) during the acute, delayed and overall phase and daily in each cycle; • Complete protection (no emetic episode, no rescue medication and no significant nausea) during the acute, delayed and overall phase and daily in each cycle • Nausea and Vomiting-related quality of life indicators (through the Functional Living Index Emesis scale) • Collection of chemotherapy delays and/or dose reductions (Delay of chemotherapy administration due to CINV will be also evaluated as part of health economic endpoints, see below) ClNV outcomes data will be prospectively collected over the first 5 days of chemotherapy and for three consecutive cycles using standardized Patient's diaries translated in local languages
The following health economic endpoints will be evaluated during the study cycles: • Number of days and daily doses of rescue medication administered for the treatment of CINV • Number of re-hydration bags given for at least grade 2 vomiting (CTCAE vS) • The number of days of unplanned hospitalisations related to CINV and department of hospitalization (type of ward) • The number of outpatient physician visits and health care consultations due to CINV (e.g., general practitioner) • The number of unplanned laboratory test including those at unplanned hospitalisations due to CINV • Discontinuation of chemotherapy treatment due to CINV • Delay of chemotherapy administration due to CINV • Days of absence from work |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Complete response during the acute (0-24h}, delayed phase (25-120h), overall (0-120h) and daily in each cycle |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
China |
Czech Republic |
Germany |
Greece |
Switzerland |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 31 |