Clinical Trial Results:
A multi-center, open-label clinical trial to evaluate the objective response rate of bevacizumab in combination with modified FOLFOX-6 followed by one year of maintenance with bevacizumab alone in patients with initially not or borderline resectable colorectal liver metastases (The CLMO-001 Trial).
|
Summary
|
|
EudraCT number |
2011-001364-22 |
Trial protocol |
IT |
Global end of trial date |
18 May 2016
|
|
Results information
|
|
Results version number |
v3(current) |
This version publication date |
02 Jun 2017
|
First version publication date |
07 Aug 2016
|
Other versions |
v1 , v2 |
Version creation reason |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
ML25625
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01383707 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
F. Hoffmann-La Roche AG
|
||
Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
|
||
Public contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
|
||
Scientific contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
18 May 2016
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
18 May 2016
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
To evaluate the activity and efficacy of modified FOLFOX-6 (levofolinic acid, 5-Fluorouracil [5-FU] and oxaliplatin) + bevacizumab regimen in terms of objective response rate (ORR) in subjects with colorectal liver metastases.
|
||
Protection of trial subjects |
All study subjects were required to read and sign an Informed Consent Form.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Aug 2011
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Efficacy, Safety | ||
Long term follow-up duration |
1 Years | ||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Italy: 77
|
||
Worldwide total number of subjects |
77
|
||
EEA total number of subjects |
77
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
34
|
||
From 65 to 84 years |
43
|
||
85 years and over |
0
|
||
|
|||||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||||
Recruitment details |
- | ||||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||||
Screening details |
Subjects with histologically confirmed adenocarcinoma of the colon or rectum with measurable metastatic disease confined to the liver were enrolled. In case of primitive rectal tumour, those with metachronous metastases or with synchronous metastases could be enrolled (if primitive lesion was > 12 cm from anal margin). | ||||||||||||||||||||
|
Period 1
|
|||||||||||||||||||||
Period 1 title |
Overall Period
|
||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||
|
Arms
|
|||||||||||||||||||||
|
Arm title
|
Bevacizumab + mFOLFOX-6 | ||||||||||||||||||||
Arm description |
Subjects received combination therapy of bevacizumab 5 milligram/kilogram (mg/kg) intravenously (IV) and mFOLFOX-6 (levofolinic acid, 5-FU and oxaliplatin) on Day 1 of every 2 weeks’ cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability underwent a liver metastasectomy. Thereafter participants received combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy). | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
5-Fluorouracil (5-FU)
|
||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||
Other name |
|||||||||||||||||||||
Pharmaceutical forms |
Solution for infusion
|
||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||
Dosage and administration details |
Subjects received 5-FU 400 mg per metre-squared (mg/m^2) IV dose on Day 1 of each 2 weeks’ cycle followed by 2400 mg/m^2, continuous infusion over 46 hours up to 12 cycles.
|
||||||||||||||||||||
Investigational medicinal product name |
Bevacizumab
|
||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||
Other name |
Avastin
|
||||||||||||||||||||
Pharmaceutical forms |
Concentrate and solvent for solution for infusion
|
||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||
Dosage and administration details |
Subjects received 5 mg/kg bevacizumab IV on Day 1 every 2 weeks.
|
||||||||||||||||||||
Investigational medicinal product name |
Levofolinic acid
|
||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||
Other name |
|||||||||||||||||||||
Pharmaceutical forms |
Solution for infusion
|
||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||
Dosage and administration details |
Subjects received levofolinic acid 200 mg per metre-squared (mg/m^2) IV infusion over 2 hours on Day 1 of each 2 weeks’ cycle up to 12 cycles.
|
||||||||||||||||||||
Investigational medicinal product name |
Oxaliplatin
|
||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||
Other name |
|||||||||||||||||||||
Pharmaceutical forms |
Powder and solvent for solution for infusion
|
||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||
Dosage and administration details |
Subjects received oxaliplatin 85 mg per metre-squared (mg/m^2) IV infusion over 2 hours on Day 1 of each 2 weeks’ cycle up to 12 cycles.
|
||||||||||||||||||||
|
|||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Bevacizumab + mFOLFOX-6
|
|||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received combination therapy of bevacizumab 5 milligram/kilogram (mg/kg) intravenously (IV) and mFOLFOX-6 (levofolinic acid, 5-FU and oxaliplatin) on Day 1 of every 2 weeks’ cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability underwent a liver metastasectomy. Thereafter participants received combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy). | |||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Bevacizumab + mFOLFOX-6
|
||
Reporting group description |
Subjects received combination therapy of bevacizumab 5 milligram/kilogram (mg/kg) intravenously (IV) and mFOLFOX-6 (levofolinic acid, 5-FU and oxaliplatin) on Day 1 of every 2 weeks’ cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability underwent a liver metastasectomy. Thereafter participants received combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy). | ||
|
|||||||||
End point title |
Objective Response Rate (ORR) in the Intent-to-treat (ITT) Analysis Set [1] | ||||||||
End point description |
ORR was defined as the percentage of subjects with shrinkage (partial response [PR]) or disappearance of cancer (complete response [CR]). Tumour response was evaluated according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). The same method of tumour measurement and assessment had to be used to characterize each lesion throughout the study. Tumour assessment consisted of computerized tomography (CT) scan (abdomen + pelvis + chest) or contrast-enhanced magnetic resonance imaging (CE-MRI) (abdomen + pelvis) + non CE-CT (chest) according to the choice of the center. CR, Disappearance of all target lesions; PR, >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Analysis Population: The ITT set, which included all enrolled subjects, who received at least one dose of any study medication.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Up to 11 cycles of treatment (up to Week 22)
|
||||||||
| 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: No statistical analyses were reported as this study only has one arm. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Objective Response Rate (ORR) in the Per-protocol Analysis Set (PPAS) [2] | ||||||||
End point description |
ORR was defined as the percentage of subjects with shrinkage (PR) or disappearance of cancer (CR). Tumour response was evaluated according to the RECIST v1.1. The same method of tumour measurement and assessment had to be used to characterize each lesion throughout the study. Tumour assessment consisted of CT scan (abdomen + pelvis + chest) or CE-MRI (abdomen + pelvis) + non CE-CT (chest) according to the choice of the center. CR, Disappearance of all target lesions; PR, >=30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR. Analysis Population: The PPAS included all subjects in the ITT set, who did not experience any major protocol violations.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Up to 11 cycles of treatment (up to Week 22)
|
||||||||
| 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: No statistical analyses were reported as this study only has one arm. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Subjects Achieving No Residual Tumor (R0)/Surgical Margin With Microscopic Residual Tumor (R1) Liver Resection | ||||||||
End point description |
The percentage of subjects achieving R0/R1 liver resection was defined as the percentage of subjects achieving R0 surgery (no residual tumour) plus percentage of subjects achieving R1 surgery (surgical margin with microscopic residual tumour). Analysis Population: The ITT set, which included all enrolled subjects, who received at least one dose of any study medication.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
End of study up to approximately 3 years
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Disease-free Interval (DFI) | ||||||||
End point description |
DFI was defined as the time from the date of R0/R1 surgery to the date of disease relapse or death due to any cause. Subjects who did not progress were considered censored at the date of the last assessment performed. For subjects receiving two-stage resection, the date of R0/R1 surgery was the date of the second surgery. Subjects, who did not receive surgery and subjects without R0/R1 surgery were censored at Day 1. DFI was calculated as follows: DFI (months ) = ([Date of R0/R1 surgery ‐ Date of 1st relapse/Death] + 1)/30 Analysis Population: The ITT set, which included all enrolled subjects, who received at least one dose of any study medication.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
End of study up to approximately 3 years
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Progression-Free Survival (PFS) | ||||||||
End point description |
PFS was defined as the time from the date of first study drug administration to the date of disease progression or death due to any cause, whichever came first. Progression was defined according to RECIST, v1.1 as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions. Subjects, who did not progress were censored at the date of the last assessment. Subjects who withdrew from the study without documented progression and for whom an electronic case report form (eCRF) existed as evidence that evaluations had been made, were censored at the date of the last tumour assessment when the subject was known to be progression-free. Subjects without post-baseline tumour assessments, but known to be alive were censored at the time of first study drug administration. PFS was calculated: PFS (months) = ([Date of Event - Date of first study drug administration] + 1)/30. Analysis population: ITT.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
End of study up to approximately 3 years
|
||||||||
|
|||||||||
| Notes [3] - The ITT set included all enrolled subjects, who received at least one dose of any study medication. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Overall Survival (OS) | ||||||||
End point description |
OS was defined as the time from the date of first study drug administration to the date of death due to any cause. Subjects who were alive at the time of the analysis were censored at the last date the subject was known to be alive. OS was calculated as follows: OS (months) = ([Date of Death - first study drug administration] + 1)/30 Analysis Population: The ITT set, which included all enrolled subjects, who received at least one dose of any study medication. 999: The median overall survival time and its 95% confidence interval were not estimable because of the low number of events (less than 50%) and of the distribution of censored subjects over time.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
End of study up to approximately 3 years
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
End of study up to approximately 3 years
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
The safety analysis set (SAF) included all enrolled subjects, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Bevacizumab + mFOLFOX-6
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received combination therapy of bevacizumab 5 mg/kg intravenously (IV) and mFOLFOX-6 (Levofolinic acid, 5-FU and oxaliplatin) on Day 1 of every 2 weeks’ cycle for 5 cycles (Cycle 1-5), followed by 1 cycle (Cycle 6) of mFOLFOX6 alone (preoperative treatment phase). After 3 weeks of preoperative treatment phase, participants satisfying the surgical criteria for hepatic resectability underwent a liver metastasectomy. Thereafter participants received combination therapy of mFOLFOX-6 + bevacizumab for another 6 cycles (Cycle 7-12); (post-operative treatment phase) followed by bevacizumab alone for 52 weeks (26 cycles) (maintenance therapy). Analysis Population: The safety analysis set (SAF) included all enrolled participants, who received at least one dose of any study medication. If there was any doubt whether a subject was treated or not, they were to be assumed treated for the purposes of analysis. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
18 Oct 2012 |
Some inclusion and exclusion criteria were modified to better align the protocol with clinical practice and Response Evaluation Criteria In Solid Tumors (RECIST). Screening procedures performed as part of the routine clinical practice before the informed consent signature did not need to be repeated in case they had been performed recently and in the same facility where the subsequent assessments were expected to be performed. During the follow-up phase, visit and evaluations (physical, haematology and tumour) could be performed ± 3 weeks from the scheduled dates. All AEs for which the intensity grade changed from the onset to the outcome, were to be registered in Electronic Case Report Form (eCRF) with the Start date and the End Date of the whole period during which they occurred and only the highest intensity detected for the AE in the whole period should have been registered. The postoperative chemotherapy + bevacizumab restart could be delayed, only for medical reasons, till a maximum of total 8 weeks after surgery. If chemotherapy + bevacizumab treatment did not restart within 8 weeks after surgery, subject had to be discontinued from the study. Defined the acceptable timeframe occurring between the end of the adjuvant treatment and the enrolment. Clarified target and non-target lesions and data requested in the eCRF. Timeline for the reporting of Serious Adverse Events and Pregnancies was modified to ‘within 24 hours’ in order to align the protocol to EU “Detailed Guidance on the collection, verification and presentation of adverse event/reaction reports arising from clinical trials on medicinal products for human use” (“CT-3”) published in June 2011. A per-protocol analysis set (PPAS) has been defined in the statistical methods. Statistical methods for laboratory data were updated according to the criteria for collecting laboratory data at post-baseline visits. Change from folinic acid to levofolinic acid was applied to specify the correct chemical structure. |
||
24 Oct 2013 |
The length of the study and the expected end of the study were updated. Risk-management plans were to be continually modified and updated throughout the lifetime of the medicine as new information became available, according to European Medicines Agency (EMA) requirements. The protocol section “Reporting of Serious Adverse Events (immediately reportable)” was updated to define the correct timelines of report. Moreover, Adverse Events of Special Interest (AESI) were added. The section “FOLFOX-6 and mFOLFOX-6 + Bevacizumab: Dose Modifications” was updated to clarify the management of drug related haematological toxicities. Changes of planned analyses: 1) Magnetic Resonance Imaging (MRI) exploratory evaluation: only subjects with assessments at both baseline and Day 14 were evaluated; 2) Haematology and Blood Chemistry Laboratory analysis: no shift table in the laboratory values according to normal range criteria was provided; 3) Unplanned analysis on primary endpoint: the final analysis was planned at the end of the study defined in the protocol as “the last subject last visit at the end of the follow-up period”. However, after the Sponsor request the final primary efficacy analysis was foreseen and provided within the first quarter of 2016. The analysis was also focused on the first 12 cycles of study. The following changes to analyses planned in the final Statistical Analysis Plan (SAP) were made effective: A post-hoc analysis of the duration of follow-up was performed. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
