Clinical Trial Results:
An Open-Label, Single-Arm, Phase II Study to Evaluate the Efficacy and the Feasibility of Bevacizumab (Avastin®) Based on a FOLFOXIRI Regimen Until Progression in Patients with Previously Untreated Metastatic Colorectal Carcinoma (OPAL-Study)
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Summary
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EudraCT number |
2008-001180-11 |
Trial protocol |
DE |
Global end of trial date |
20 Feb 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
31 May 2020
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First version publication date |
31 May 2020
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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 |
ML20514
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00940303 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
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Public contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Scientific contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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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 |
20 Feb 2014
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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 |
20 Feb 2014
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
Evaluation of progression-free survival (PFS) of bevacizumab combined with treatment regimen consisting of 5-fluorouracil (5-FU)/folinic acid (FA), oxaliplatin and irinotecan (FOLFOXIRI) regimen in subjects with previously untreated metastatic colorectal carcinoma.
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Protection of trial subjects |
All study subjects were required to read and sign an informed consent form.
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Background therapy |
Treatment with 5-FU/FA, oxaliplatin and irinotecan (FOLFOXIRI) administered by intravenous (IV) infusion for 12 cycles once every 2 weeks, followed by up to 40 cycles once every 2 weeks of 5-FU/FA IV infusion. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Jul 2009
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
3 Years | ||
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 |
Germany: 90
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Worldwide total number of subjects |
90
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EEA total number of subjects |
90
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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) |
63
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From 65 to 84 years |
27
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were recruited at study sites in Germany. | ||||||||||||||
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Pre-assignment
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Screening details |
Participants with histologically confirmed diagnosis of metastatic colorectal carcinoma (CRC) according to Response Evaluation Criteria in Solid Tumors Response Evaluation Criteria in Solid Tumors (RECIST) criteria were eligible for the study. | ||||||||||||||
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Period 1
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Period 1 title |
Overall study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Bevacizumab | ||||||||||||||
Arm description |
Participants received IV infusion of bevacizumab on Day 1 of each cycle prior to the infusion of background medication for up to 52 cycles once every 2 weeks. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
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 for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
5 milligram per kilogram (mg/kg) body weight administered as IV infusion on Day 1 of each cycle prior to the infusion of background medication for up to 52 cycles once every 2 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Bevacizumab
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Reporting group description |
Participants received IV infusion of bevacizumab on Day 1 of each cycle prior to the infusion of background medication for up to 52 cycles once every 2 weeks. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Bevacizumab
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Reporting group description |
Participants received IV infusion of bevacizumab on Day 1 of each cycle prior to the infusion of background medication for up to 52 cycles once every 2 weeks. | ||
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End point title |
Progression Free Survival (PFS) [1] | ||||||||
End point description |
PFS is defined as the time from the start of treatment to disease progression (PD), relapse or death from any cause, whichever occurs first, as per the Response Evaluation Criteria in Solid Tumors (RECIST). PD was defined as a 20 percent or greater increase in the sum of the longest diameter of the target lesions taking as reference the smallest sum longest diameter recorded or appearance of new lesions. Intent-to-treat (ITT) population included all participants who had received at least one dose of the study medication.
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End point type |
Primary
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End point timeframe |
From start of treatment up to disease progression or relapse or death, whichever occurred first (up to approximately 55 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: Only descriptive statistics were planned for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall survival (OS) | ||||||||
End point description |
OS is defined as the time from the start of study treatment to death from any cause. ITT population included all participants who had received at least one dose of the study medication.
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End point type |
Secondary
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End point timeframe |
From start of treatment up to death of any cause (approximately 55 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Among Resected Participants Who Had R0 Resection | ||||||||
End point description |
Reported here is the percentage of participants who had curative (R0) resection among those participants who were resected during the study. The population analyzed here included participants who had received at least one dose of the study medication and who had undergone tumor resection during the study.
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End point type |
Secondary
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End point timeframe |
Up to approximately 55 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Objective Response Rate | ||||||||
End point description |
ORR was defined as the percentage of participants with complete response (CR) or partial response (PR) per RECIST criteria. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis <10 millimetres [mm]). No new lesions. PR was defined as at least 30 percent decrease under baseline of the sum of diametres of all target lesions. The short axis was used in the sum for target nodes, while the longest diametre was used in the sum for all other target lesions. ITT population included all participants who had received at least one dose of the study medication.
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End point type |
Secondary
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End point timeframe |
From start of treatment until disease progression (up to approximately 55 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Best Overall Response Rate | ||||||||
End point description |
Best overall response was defined as the percentage of participants with CR + PR + stable disease (SD) per RECIST criteria. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis <10 millimetres [mm]). No new lesions. PR was defined as at least 30 percent decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. ITT population included all participants who had received at least one dose of the study medication.
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End point type |
Secondary
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End point timeframe |
Treatment start until disease progression/recurrence (up to approximately 55 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Overall Response | ||||||||
End point description |
Duration of overall response was defined as the time from first documented objective response (CR or PR), whichever status was recorded first until the first date on which recurrence or PD was objectively documented. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis <10 millimetres [mm]). No new lesions. PR was defined as at least 30 percent decrease under baseline of the sum of diametres of all target lesions. The short axis was used in the sum for target nodes, while the longest diametre was used in the sum for all other target lesions. ITT Population included all participants who had received at least one dose of the study medication.
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End point type |
Secondary
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End point timeframe |
Treatment start until disease progression/recurrence (approximately 55 months)
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| Notes [2] - Number of participants analysed are the participants who were evaluated for the endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants with Change in Eastern Cooperative Oncology Group (ECOG) Performance Status | ||||||||||||||
End point description |
ECOG performance status was assessed by investigator as 0: fully active, able to carry out all pre-disease performance without restriction, 1: restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light housework office work, 2: restricted physical activity, capable of all self-care, but unable to carry out any work activities. Up and about >50 of waking hours, 3: capable of only limited self-care; confined to bed or chair >50% of waking hours. 4: completely disabled; cannot carry out any self-care; totally confined to bed or chair. ITT population included all participants who had received at least one dose of the study medication.
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End point type |
Secondary
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End point timeframe |
Screening, Safety Follow up (up to Week 107)
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| Notes [3] - Number of participants analysed are the participants who were evaluated for the endpoint. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Number of Treatment Cycles with Study Medication | ||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Up to end of treatment period (up to Week 103)
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Percentage of Participants with Adverse Events (AEs) | ||||||||
End point description |
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Safety population included all participants who received at least one dose of the study medication and had at least one safety follow-up, regardless whether the trial medication was prematurely withdrawn or not.
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End point type |
Secondary
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End point timeframe |
Up to approximately 55 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants with Adverse Events of Special Interest (AESIs) | ||||||||
End point description |
AESIs were defined as diarrhoea of grade 2 according to the National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) v3.0 as well as any grade of gastrointestinal perforation, gastrointestinal fistulas or other internal fistulas, wound-healing disturbances, haemorrhagic events and arterial thromboembolic events. Safety population included all participants who received at least one dose of the study medication and had at least one safety follow-up, regardless whether the trial medication was prematurely withdrawn or not.
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End point type |
Secondary
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End point timeframe |
Up to approximately 55 months
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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 |
Up to approximately 55 months
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Adverse event reporting additional description |
Safety population was defined as the participants who received at least one dose of the study medication and had at least one safety follow-up, regardless whether the trial medication was prematurely withdrawn or not.
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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 |
14.1
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Reporting groups
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Reporting group title |
Bevacizumab
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Reporting group description |
Participants received IV infusion of bevacizumab on Day 1 of each cycle prior to the infusion of background medication for up to 52 cycles once every 2 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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15 Dec 2008 |
For clarity the term “bi-weekly” was replaced by the term “once every 2 weeks” in the dosing regimen. During the treatment phase response evaluation, including surgical evaluation, was performed according to RECIST criteria every 8 weeks. Criteria that should lead to discontinuation or early termination of the study were described in more detail. |
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12 Sep 2013 |
The sections of the study protocol about early study termination were amended. |
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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 | |||||||
