Clinical Trial Results:
A multicentre, single-arm, phase II study to investigate the safety and antiemetic efficacy of Akynzeo® (a fixed dose combination of palonosetron and netupitant) plus dexamethasone in patients receiving concomitant chemo-radiotherapy with weekly cisplatin for at least five weeks.
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Summary
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EudraCT number |
2017-004031-37 |
Trial protocol |
DK |
Global end of trial date |
21 Feb 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Jun 2025
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First version publication date |
19 Jun 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
17.14
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03668639 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Department og oncology, Odense University Hospital
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Sponsor organisation address |
Kløvervænget 10, indgang 112, 5 sal, Odense C, Denmark, 5000
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Public contact |
Christina H Bruvik Ruhlmann , Department of oncology, Odense University Hospital, 0045 65413349, christina.ruhlmann@rsyd.dk
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Scientific contact |
Christina H Bruvik Ruhlmann , Department of oncology, Odense University Hospital, 0045 65413349, christina.ruhlmann@rsyd.dk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
02 Feb 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
02 Feb 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Feb 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
1. The first co-primary objective is to explore the safety of an antiemetic regimen consisting of Akynzeo and dexamethasone during five weeks of fractionated (5 days a week) radiotherapy and concomitant weekly cisplatin at a dose of ≥ 40 mg/m2.
2. The second co-primary objective investigate Akynzeo and dexamethasone in terms of the proportion of subjects with no vomiting, i.e. sustained no emesis rate - during five weeks of fractionated radiotherapy and concomitant weekly cisplatin at a dose of ≥ 40 mg/m2.
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Protection of trial subjects |
A signed, written informed consent was obtained prior to any study procedures or assessments being initiated. The study was approved by the Ethics Committee (Acadre number: 17/35157) and the Danish Medicines Agency (EudraCT number: 2017-004031-37). It was conducted in accordance with the principles of Good Clinical Practice, as well as all applicable patient privacy requirements in Denmark (protection by the "Act on Processing of Personal Data" and the "Health Care Act"), and the guiding principles of the Declaration of Helsinki. Data were entered into a logged, web-based REDCap database hosted by Open Patient data Explorative Network (OPEN), Odense, Denmark.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
08 Oct 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 73
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Worldwide total number of subjects |
73
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EEA total number of subjects |
73
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
61
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From 65 to 84 years |
12
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were recruited from two departments of oncology in Denmark. From October 8, 2018, to January 2, 2024, 154 patients were screened, and 73 patients were eligible and received at least one dose of the study medication. | ||||||||||||||||
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Pre-assignment
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Screening details |
Patients with a diagnosis of cervical cancer, naïve to chemo- and radiotherapy and who are scheduled to receive fractionated radiotherapy and concomitant weekly cisplatin at a dose of ≥ 40 mg/m2 for at least five weeks, will be screened for eligibility and asked for study participation when the patients attend a planned visit. | ||||||||||||||||
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Period 1
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Period 1 title |
Recruitment (Overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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netupitant/palonosetron plus dexamethasone | ||||||||||||||||
Arm description |
Intention to treat | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Dexamethason
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Investigational medicinal product code |
PR1
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Day 1, weeks 1-5
• At one hour prior to cisplatin ≥ 40 mg/m2, the subject will be administered Akynzeo (netupitant 300 mg / palonosetron 0.5 mg) orally and 30 minutes before cisplatin 3 tablets of dexamethasone 4 mg, 12 mg in total.
Days 2-3, weeks 1-5
• The subject will be instructed to take 2 tablets dexamethasone from the bottle to a total of 8 mg, in the morning on Days 2-3.
Day 4, weeks 1-5
• The subject will be instructed to take 1 tablet of dexamethasone 4 mg from the bottle in the morning on Day 4.
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Investigational medicinal product name |
Akynzeo
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Investigational medicinal product code |
PR2
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Other name |
Palonosetron Hydrochloride
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Day 1, weeks 1-5
• At one hour prior to cisplatin ≥ 40 mg/m2, the subject will be administered Akynzeo (netupitant 300 mg / palonosetron 0.5 mg) orally and 30 minutes before cisplatin 3 tablets of dexamethasone 4 mg, 12 mg in total.
Days 2-3, weeks 1-5
• The subject will be instructed to take 2 tablets dexamethasone from the bottle to a total of 8 mg, in the morning on Days 2-3.
Day 4, weeks 1-5
• The subject will be instructed to take 1 tablet of dexamethasone 4 mg from the bottle in the morning on Day 4.
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Baseline characteristics reporting groups
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Reporting group title |
Recruitment (Overall period)
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Reporting group description |
- | ||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
netupitant/palonosetron plus dexamethasone
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Reporting group description |
Intention to treat | ||
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End point title |
Safety of the antiemetic regimen NEPA and DEX [1] | ||||||||||||
End point description |
TRAEs occurring in ≥ 2% of patients are shown. No grade 4 or 5 TRAEs were observed. The column All grades represents the number of patients with grade 1, 2, and/or 3 TRAEs, counted once per patient regardless of the number of different grades experienced.
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End point type |
Primary
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End point timeframe |
The proportion of patients experiencing Treatment Related Adverse Events(TRAEs) measured from the first dose of study medication to the end of cycle 5.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Safety were assessed using descriptive analyses on the intention-to-treat (ITT) population, consisting of all patients who received at least one dose of study medication and had at least one AE registration after treatment administration. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
proportion of subjects with no vomiting (i.e. sustained no emesis rate) [2] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
five weeks after initiating chemo-radiotherapy
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The co-primary outcome regarding efficacy was described using a Kaplan–Meier plot showing the cumulative incidence of patients (ITT population) who sustained no emesis after initiating chemo-radiotherapy. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean time to first emetic episode | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Measured from first dose tof study drug until last AE-evaluation (days)
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| No statistical analyses for this end point | |||||||||
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End point title |
Complete respons | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Proportion of patients with Complete respons during Day 1-5 and Day 1-35.
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| No statistical analyses for this end point | |||||||||||
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End point title |
No vomiting | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
No vomiting episodes experienced between first dose and day 35.
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| No statistical analyses for this end point | |||||||||||
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End point title |
No significant nausea | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
From first dose to day 35
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| No statistical analyses for this end point | |||||||||||
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End point title |
No nausea | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
From first dose to day 35.
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| No statistical analyses for this end point | |||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
The follow-up period was defined as the period from the first study drug dose to the last AE evaluation.
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Adverse event reporting additional description |
Investigators evaluated a list of 34 items representing potential adverse events (AEs) and their relation to the study drug at baseline (prior to study initiation). AEs were considered treatment-related adverse events (TRAEs) if the relationship to NEPA or NEPA/DEX was deemed as definitely, probably or possibly related, or if it was missing.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
5.0
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Reporting groups
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Reporting group title |
Intention to treat group
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 2% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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19 May 2023 |
Amended in protocol version 3.
Inclusion will end December 31, 2023, and End of Study (follow -up completed for all subjects) will be February 26, 2024. The number of enrolled patients at End of Study will constitute the ITT population. This is a descriptive and non-comparative study (no null hypothesis to test), and therefore the 61 eligible patients will be equal to the ITT population in order to reflect the real world setting w here patients do not necessarily receive 5 cycles/w eeks of chemotherapy and hence antiemetics/study drug. The ITT population will form the basis for all safety data analyses. Efficacy data analyses will be performed based on both the ITT population and on the primary per-protocol cohort (completing five cycles/weeks of chemotherapy/antiemetics/study drug). |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| None reported | |||||||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/40437122 |
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