Clinical Trial Results:
Lonsurf - RII
Lonsurf (TAS-102) with or without bevacizumab in patients with chemo-refractory metastatic colorectal cancer.
A randomized phase II study
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Summary
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EudraCT number |
2016-005241-23 |
Trial protocol |
DK |
Global end of trial date |
24 Jun 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Jan 2022
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First version publication date |
26 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 |
16.37
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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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,
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Public contact |
Ida Coordt Elle, Odense Universitetshospital, 45 29335922, ida.coordt.elle@rsyd.dk
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Scientific contact |
Per Pfeiffer, Odense Universitetshospital, 45 26283844, per.pfeiffer@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 |
24 Jun 2019
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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 |
24 Jun 2019
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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 |
Primary objective:
• Progression-free survival (PFS)
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Protection of trial subjects |
Pre-medication was administered to minimize adverse events and discomfort.
A safety analysis focusing on toxicity, treatment
duration, and dose intensity was done when the first
42 patients had completed two cycles of therapy.
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Background therapy |
- | ||
Evidence for comparator |
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Actual start date of recruitment |
24 Aug 2017
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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 |
Denmark: 93
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Worldwide total number of subjects |
93
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EEA total number of subjects |
93
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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) |
46
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From 65 to 84 years |
47
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85 years and over |
0
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Recruitment
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Recruitment details |
Eligible patients were aged 18 years or older with histopathologically confirmed colorectal adenocarcinoma, had non-resectable metastatic colorectal cancer, had a WHO performance status of 0 or 1, had a life expectancy of at least 3 months, and were refractory or intolerant to fluoropyrimidines, irinotecan, oxaliplatin, and cetuximab or panitumumab | |||||||||
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Pre-assignment
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Screening details |
Liver and renal function had to be within normal ranges and bilirubin no higher than 1·5-times the upper limit of normal, glomerular filtration rate above 50 mL/min, neutrophil cell count of at least 1·5 × 10⁹ cells per L, and a platelet count of at least 100 × 10⁹ per L. | |||||||||
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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 | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Lonsurf | |||||||||
Arm description |
Monotherapy with TAS-102 35 mg/m² orally twice daily on days 1–5 and 8–12 every 28 days. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
trifluridine-tipiracil
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Investigational medicinal product code |
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Other name |
Lonsruf, TAS-102
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
35 mg/m² orally twice daily on days 1–5 and 8–12 every 28 days.
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Arm title
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Lonsurf+bevacizumab | |||||||||
Arm description |
Lonsurf 35 mg/m² orally twice daily on days 1–5 and 8–12 every 28 days. Bevacizumab (5 mg/kgintravenously) on days 1 and 15 every 28 days. The bevacizumab dose was administered as a 30-min intravenous infusion before the TAS-102 dose. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
trifluridine-tipiracil
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Investigational medicinal product code |
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Other name |
Lonsruf, TAS-102
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
35 mg/m² orally twice daily on days 1–5 and 8–12 every 28 days.
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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 |
Solution for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
(5 mg/kg intravenously) on days 1 and 15 every 28 days.
The bevacizumab dose was administered as a 30-min intravenous infusion before the TAS-102 dose.
If dose reduction was needed during treatment because of toxicity, the dose of TAS-102 was reduced in increments of 5 mg/m². If patients had unacceptable toxicities related to bevacizumab, treatment with TAS-102 monotherapy could be continued according to protocol
without bevacizumab. Dose reduction of bevacizumab was not recommended.
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Baseline characteristics reporting groups
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Reporting group title |
Lonsurf
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Reporting group description |
Monotherapy with TAS-102 35 mg/m² orally twice daily on days 1–5 and 8–12 every 28 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lonsurf+bevacizumab
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Reporting group description |
Lonsurf 35 mg/m² orally twice daily on days 1–5 and 8–12 every 28 days. Bevacizumab (5 mg/kgintravenously) on days 1 and 15 every 28 days. The bevacizumab dose was administered as a 30-min intravenous infusion before the TAS-102 dose. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Lonsurf
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Reporting group description |
Monotherapy with TAS-102 35 mg/m² orally twice daily on days 1–5 and 8–12 every 28 days. | ||
Reporting group title |
Lonsurf+bevacizumab
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Reporting group description |
Lonsurf 35 mg/m² orally twice daily on days 1–5 and 8–12 every 28 days. Bevacizumab (5 mg/kgintravenously) on days 1 and 15 every 28 days. The bevacizumab dose was administered as a 30-min intravenous infusion before the TAS-102 dose. | ||
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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 |
24 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 publication for complete 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 |
30 days after last treatment
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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 |
22.1
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Reporting groups
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Reporting group title |
Lonsurf
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Reporting group description |
Monotherapy with TAS-102 35 mg/m² orally twice daily on days 1–5 and 8–12 every 28 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lonsurf+bevacizumab
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Reporting group description |
Lonsurf 35 mg/m² orally twice daily on days 1–5 and 8–12 every 28 days. Bevacizumab (5 mg/kgintravenously) on days 1 and 15 every 28 days. The bevacizumab dose was administered as a 30-min intravenous infusion before the TAS-102 dose. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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11 Jul 2017 |
CT scan after cycle 1.
CBC deleted.
Use of OPEN facilities for randomization and eCRF.
Bevacizumab dose modification section added.
Monitoring of SUSARs deleted.
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15 Nov 2017 |
Hillerød, Rigshospitalet and Sønderborg sites added.
Baseline scan should be maximum two weeks old instead of four.
Hematology blood samples on day 15 for both arms.
Maximum eight days between registration and treatment start.
Examples added to exclusion criterion.
Minor corrections.
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12 Dec 2017 |
Hillerød site removed from protocol.
Changes in section 7 regarding personnel handling medication.
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03 Aug 2018 |
Inclusion of 124 patients instead of 80 patients. |
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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/31999946 |
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