Clinical Trial Results:
Full dose S-1 monotherapy compared to reduced dose S-1/oxaliplatin combination therapy as first-line treatment for older patients with metastatic colorectal cancer.
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Summary
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EudraCT number |
2014-000394-39 |
Trial protocol |
DK NO FI |
Global end of trial date |
01 Sep 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Jan 2022
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First version publication date |
19 Jan 2022
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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 |
KFE 14.01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Odense University Hospital
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Sponsor organisation address |
J. B. Winsløws Vej 4, entrance 140, basemenet, Odense C, Denmark, 5000
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Public contact |
Ida Coordt Elle, Odense University Hospital, +45 29335922, ida.coordt.elle@rsyd.dk
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Scientific contact |
Stine Brændegaard Winther, Odense University Hospital, +45 28601058, stine.winther@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 |
01 Sep 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Sep 2018
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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 |
Progression-free survival (PFS)
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Protection of trial subjects |
Pre-medication was administered to minmize adverse reactions.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 Feb 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Norway: 57
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Country: Number of subjects enrolled |
Sweden: 51
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Country: Number of subjects enrolled |
Denmark: 43
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Country: Number of subjects enrolled |
Finland: 9
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Worldwide total number of subjects |
160
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EEA total number of subjects |
160
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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) |
0
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From 65 to 84 years |
153
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85 years and over |
7
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Recruitment
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Recruitment details |
Eligible patients were aged 70 years or older and had histopathologically proven colorectal adenocarcinoma, non-resectable metastases, and a WHO performance status of 0–2. | |||||||||
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Pre-assignment
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Screening details |
Participants had received no prior chemotherapy except adjuvant fluoropyrimidine therapy completed more than 180 days before randomisation and had a life expectancy of at least 3 months. | |||||||||
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Period 1
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Period 1 title |
Trial period (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
Blinding implementation details |
Patients were randomly assigned to sequential full-dose monotherapy (S-1 followed by irinotecan monotherapy at progression) or sequential dose-reduced combination chemotherapy (S-1 and oxaliplatin followed by S-1 and irinotecan at progression). Bevacizumab was optional in first-line therapy at the discretion of the treating physician but the decision had to be made before randomisation.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Full-dose monotherapy | |||||||||
Arm description |
Patients assigned to full-dose monotherapy were treated with S-1 30 mg/m² orally twice daily on days 1–14 every 3 weeks followed by second-line treatment at progression with irinotecan (250 mg/m² intravenously on day 1 every 3 weeks or 180 mg/m² intravenously on day 1 every 2 weeks). In the absence of toxicity above grade 1 (except alopecia), it was recommended to increase irinotecan in steps to 350 mg/m² intravenously on day 1 every 3 weeks or 250 mg/m² intravenously on day 1 every 2 weeks. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
S1
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Investigational medicinal product code |
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Other name |
Teysuno
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Patients assigned to full-dose monotherapy were treated with S-1 30 mg/m² orally twice daily on days 1–14 every 3 weeks followed by second-line treatment at progression with irinotecan (250 mg/m² intravenously on day 1 every 3 weeks or 180 mg/m² intravenously on day 1 every 2 weeks). In the absence of toxicity above grade 1 (except alopecia), it was recommended to increase irinotecan in steps to 350 mg/m² intravenously on day 1
every 3 weeks or 250 mg/m² intravenously on day 1 every 2 weeks.
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Arm title
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Reduced-dose combination therapy | |||||||||
Arm description |
Patients assigned to reduced-dose combination chemotherapy received S-1 20 mg/m² orally twice daily on days 1–14 and oxaliplatin 100 mg/m² intravenously on day 1 every 3 weeks followed by second-line treatment at progression with S-1 20 mg/m² orally twice daily on days 1–14 and irinotecan 180 mg/m² intravenously on day 1 every 3 weeks. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
S1
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Investigational medicinal product code |
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Other name |
Teysuno
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Patients assigned to reduced-dose combination chemotherapy received S-1 20 mg/m² orally twice daily on
days 1–14 and oxaliplatin 100 mg/m² intravenously on day 1 every 3 weeks followed by second-line treatment at progression with S-1 20 mg/m² orally twice daily on days 1–14 and irinotecan 180 mg/m² intravenously on day 1 every 3 weeks.
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Investigational medicinal product name |
Oxaliplatin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate and solvent for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Patients assigned to reduced-dose combination chemotherapy received S-1 20 mg/m² orally twice daily on
days 1–14 and oxaliplatin 100 mg/m² intravenously on day 1 every 3 weeks followed by second-line treatment at progression with S-1 20 mg/m² orally twice daily on days 1–14 and irinotecan 180 mg/m² intravenously on day 1 every 3 weeks.
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Investigational medicinal product name |
Irinotecan
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Patients assigned to reduced-dose combination chemotherapy received S-1 20 mg/m² orally twice daily on
days 1–14 and oxaliplatin 100 mg/m² intravenously on day 1 every 3 weeks followed by second-line treatment at progression with S-1 20 mg/m² orally twice daily on days 1–14 and irinotecan 180 mg/m² intravenously on day 1 every 3 weeks.
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Investigational medicinal product name |
Bevacizumab
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Investigational medicinal product code |
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Other name |
Avastin
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Pharmaceutical forms |
Concentrate and solvent for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Because bevacizumab was not standard of care in most Nordic countries at the time of study design, the addition
of bevacizumab to first-line chemotherapy was optional and given at the discretion of the treating physician. When used, bevacizumab was given at 7.5 mg/kg intravenously on day 1 every 3 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Full-dose monotherapy
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Reporting group description |
Patients assigned to full-dose monotherapy were treated with S-1 30 mg/m² orally twice daily on days 1–14 every 3 weeks followed by second-line treatment at progression with irinotecan (250 mg/m² intravenously on day 1 every 3 weeks or 180 mg/m² intravenously on day 1 every 2 weeks). In the absence of toxicity above grade 1 (except alopecia), it was recommended to increase irinotecan in steps to 350 mg/m² intravenously on day 1 every 3 weeks or 250 mg/m² intravenously on day 1 every 2 weeks. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Reduced-dose combination therapy
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Reporting group description |
Patients assigned to reduced-dose combination chemotherapy received S-1 20 mg/m² orally twice daily on days 1–14 and oxaliplatin 100 mg/m² intravenously on day 1 every 3 weeks followed by second-line treatment at progression with S-1 20 mg/m² orally twice daily on days 1–14 and irinotecan 180 mg/m² intravenously on day 1 every 3 weeks. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Full-dose monotherapy
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Reporting group description |
Patients assigned to full-dose monotherapy were treated with S-1 30 mg/m² orally twice daily on days 1–14 every 3 weeks followed by second-line treatment at progression with irinotecan (250 mg/m² intravenously on day 1 every 3 weeks or 180 mg/m² intravenously on day 1 every 2 weeks). In the absence of toxicity above grade 1 (except alopecia), it was recommended to increase irinotecan in steps to 350 mg/m² intravenously on day 1 every 3 weeks or 250 mg/m² intravenously on day 1 every 2 weeks. | ||
Reporting group title |
Reduced-dose combination therapy
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Reporting group description |
Patients assigned to reduced-dose combination chemotherapy received S-1 20 mg/m² orally twice daily on days 1–14 and oxaliplatin 100 mg/m² intravenously on day 1 every 3 weeks followed by second-line treatment at progression with S-1 20 mg/m² orally twice daily on days 1–14 and irinotecan 180 mg/m² intravenously on day 1 every 3 weeks. | ||
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End point title |
Progression-free survival [1] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Data-cut-off was 36 months.
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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: Please see the original publication for statistical analysis. |
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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 |
Last treatment + 30 days.
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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 |
21.1
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Reporting groups
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Reporting group title |
Full-dose monotherapy
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Reporting group description |
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Reporting group title |
Reduced-dose combination therapy
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 3% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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24 Jan 2014 |
Questionnaire VES13 added, Barthel deleted.
GFR clarified in relation to treatment.
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17 Feb 2014 |
Corrections and comments from authorities. |
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14 Apr 2014 |
Elaboration of Safety section.
Corrections in patient information.
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03 Nov 2014 |
Author added to the protocol committee.
General changes to protocol.
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24 Apr 2017 |
Number of patients increased from 150 to 160.
Number of sites changed, as Finland entered the study.
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08 Sep 2017 |
Extension of inclusion period until Nov. 1st 2017.
Extension of study period until LPLV May 1st 2019.
Change of PI in Herning from Nina Keldsen to Halla Skuladottir.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
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/30852136 |
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