Clinical Trial Results:
A Phase II uncontrolled study of BAY73-4506 in previously untreated patients with metastatic or unresectable renal cell cancer (RCC)
|
Summary
|
|
EudraCT number |
2008-000107-28 |
Trial protocol |
FI DE FR GB |
Global end of trial date |
02 Apr 2019
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
09 Apr 2020
|
First version publication date |
09 Apr 2020
|
Other versions |
|
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 |
11726/BAY73-4506
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT00664326 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Bayer AG
|
||
Sponsor organisation address |
Kaiser Wilhelm Allee, Leverkusen, Germany, D-51368
|
||
Public contact |
Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
|
||
Scientific contact |
Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.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 |
24 Apr 2019
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
02 Apr 2019
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The primary objective of this study was to evaluate the antitumor activity and safety of BAY 73-4506 in previously untreated subjects with metastatic or unresectable RCC.
Secondary objectives included the evaluation of pharmacokinetic and biomarker data.
|
||
Protection of trial subjects |
The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent form was read by and explained to all subjects. Participating subjects signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Apr 2008
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
10 Years | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Germany: 3
|
||
Country: Number of subjects enrolled |
United Kingdom: 24
|
||
Country: Number of subjects enrolled |
United States: 2
|
||
Country: Number of subjects enrolled |
Poland: 8
|
||
Country: Number of subjects enrolled |
France: 2
|
||
Country: Number of subjects enrolled |
Finland: 10
|
||
Worldwide total number of subjects |
49
|
||
EEA total number of subjects |
47
|
||
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) |
31
|
||
From 65 to 84 years |
18
|
||
85 years and over |
0
|
||
|
|||||||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||||||
Recruitment details |
Male or female untreated participants, who were at least 18 years of age, with metastatic and/or unresectable, measurable predominantly clear cell renal cell cancer (RCC) histologically or cytologically documented could participate in this study at 18 centers in 6 countries. | ||||||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||||||
Screening details |
Of 64 enrolled participants, 49 received study medication, and 15 were screen failures due to protocol violation (12 participants), withdrawal of consent (1 participant), adverse event (2 participants). | ||||||||||||||||||||||
|
Period 1
|
|||||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||||
|
Arms
|
|||||||||||||||||||||||
|
Arm title
|
Regorafenib (Stivarga, BAY73-4506) | ||||||||||||||||||||||
Arm description |
Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle | ||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||
Investigational medicinal product name |
Regorafenib
|
||||||||||||||||||||||
Investigational medicinal product code |
BAY73-4506
|
||||||||||||||||||||||
Other name |
|||||||||||||||||||||||
Pharmaceutical forms |
Coated tablet
|
||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||
Dosage and administration details |
BAY 73-4506, 160 mg once daily for 3 weeks of every 4-week cycle (i.e., 3 weeks on, 1 week off)
|
||||||||||||||||||||||
|
|||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Regorafenib (Stivarga, BAY73-4506)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Regorafenib (Stivarga, BAY73-4506)
|
||
Reporting group description |
Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle | ||
|
|||||||||
End point title |
Objective tumor response [1] | ||||||||
End point description |
Objective tumor response of a participant was defined as the best tumor response (confirmed Complete Response [CR, tumor disappears] or Partial Response [PR, sum of lesion sizes decreased at least 30% from baseline]) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) committee.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks
|
||||||||
| 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: Statistical analyses of this primary endpoint is descriptive |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||
End point title |
Tumor response [2] | ||||||||||||||||||
End point description |
Tumor response of a participant was defined as the best tumor response (confirmed Complete Response [CR, tumor disappears], Partial Response [PR, sum of lesion sizes decreased at least 30% from baseline], Stable Disease [SD, steady state of disease], or Progressive Disease [PD, sum of lesion sizes increased at least 20% from smallest sum on study or new lesions]) observed during trial period assessed according to the RECIST committee.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks
|
||||||||||||||||||
| 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: Statistical analyses of this primary endpoint is descriptive. |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||
End point title |
Disease control | ||||||||
End point description |
Disease control was defined as the percentage of participants who had a best response rating of CR (tumor disappears), PR (sum of lesion sizes decreased at least 30% from baseline), or SD (steady state of disease) that was maintained for at least 28 days from the first demonstration of that rating.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Overall survival | ||||||||
End point description |
Overall survival (OS) was calculated as the time from the first date of receiving study medication to death, due to any cause. Participants alive at the time of analysis were censored at their last date of follow-up.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009).
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Progression-free survival (PFS) | ||||||||
End point description |
PFS was calculated as time from first date of receiving study drug until date of first observed disease progression (PD) (radiological or clinical, whichever was earlier) or death due to any cause, if death occurred before PD was documented. The actual date of tumor assessments (i.e., date on which radiological procedure was performed, rather than scheduled date) was used for this calculation to determine both the event date and censoring date. Patients without PD or death at time of analysis were censored at last date of tumor evaluation.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Time to progression (TTP) | ||||||||
End point description |
TTP was calculated as time from first date of receiving study drug until date of first documented disease progression (PD) (radiological or clinical, whichever was earlier). The actual date of tumor assessments (i.e., date on which radiological procedure was performed, rather than the scheduled date) was used for this calculation to determine both the event date and censoring date. Patients without PD at time of analysis were censored at last date of tumor evaluation.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Duration of response | ||||||||
End point description |
Duration of response was defined as the time from the first documented objective response of PR or CR, whichever was earlier, to disease progression or death (if death occurred before progression was documented). Duration of response for subjects who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Duration of stable disease (SD) | ||||||||
End point description |
Duration of SD was calculated as the time from the first date of receiving study drug until the date of documented PD or the last observation if the subject did not progress. Subjects without disease progression at the time of analysis were censored at the last date of tumor evaluation.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Objective tumor response (Update) | ||||||||
End point description |
Objective tumor response of a participant was defined as the best tumor response (confirmed Complete Response [CR, tumor disappears] or Partial Response [PR, sum of lesion sizes decreased at least 30% from baseline]) observed during trial period assessed according to the RECIST committee.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||
End point title |
Tumor response (Update) | ||||||||||||||||||
End point description |
Tumor response of a participant was defined as the best tumor response (confirmed Complete Response [CR, tumor disappears], Partial Response [PR, sum of lesion sizes decreased at least 30% from baseline], Stable Disease [SD, steady state of disease], or Progressive Disease [PD, sum of lesion sizes increased at least 20% from smallest sum on study or new lesions]) observed during trial period assessed according to the RECIST committee.
|
||||||||||||||||||
End point type |
Other pre-specified
|
||||||||||||||||||
End point timeframe |
From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||
End point title |
Disease control (Update) | ||||||||
End point description |
Disease control was defined as the percentage of participants who had a best response rating of CR (tumor disappears), PR (sum of lesion sizes decreased at least 30% from baseline), or SD (steady state of disease) that was maintained for at least 28 days from the first demonstration of that rating.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Overall survival (Update) | ||||||||
End point description |
Overall survival (OS) was calculated as the time from the first date of receiving study medication to death, due to any cause. Participants alive at the time of analysis were censored at their last date of follow-up.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011).
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Progression-free survival (Update) | ||||||||
End point description |
PFS was calculated as time from first date of receiving study drug until date of first observed disease progression (PD) (radiological or clinical, whichever was earlier) or death due to any cause, if death occurred before PD was documented. The actual date of tumor assessments (i.e., date on which radiological procedure was performed, rather than scheduled date) was used for this calculation to determine both the event date and censoring date. Patients without PD or death at time of analysis were censored at last date of tumor evaluation.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Time to progression (Update) | ||||||||
End point description |
TTP was calculated as time from first date of receiving study drug until date of first documented disease progression (PD) (radiological or clinical, whichever was earlier). The actual date of tumor assessments (i.e., date on which radiological procedure was performed, rather than the scheduled date) was used for this calculation to determine both the event date and censoring date. Patients without PD at time of analysis were censored at last date of tumor evaluation.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Duration of response (Update) | ||||||||
End point description |
Duration of response was defined as the time from the first documented objective response of PR or CR, whichever was earlier, to disease progression or death (if death occurred before progression was documented). Duration of response for subjects who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Duration of stable disease (Update) | ||||||||
End point description |
Duration of SD was calculated as the time from the first date of receiving study drug until the date of documented PD or the last observation if the subject did not progress. Subjects without disease progression at the time of analysis were censored at the last date of tumor evaluation.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From the start of study treatment up to 30 days after the last dose of study drug
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Acronyms used in Adverse events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Common Terminology Criteria for Adverse Events (CTCAE).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Regorafenib (BAY73-4506)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received regorafenib 160 mg po qd for 3 weeks of every 4 week cycle (3 weeks on, 1 week off). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 |
||
24 Jun 2008 |
A Data Monitoring Committee was added.
Clarification was provided for how the risk/benefit was to be assessed during the study and how the termination/continuation would be evaluated.
The frequency of tumor assessments after month 6 (cycle 6) was decreased from every 8 weeks to every 12 weeks.
The timing of disease assessments was clarified.
The packaging configuration for study medication was added.
Assessments (tissue and blood biomarker samples, vital signs, blood pressure, and laboratory evaluations) were clarified.
The description of Adverse Events handling was updated to reflect Bayer oncology standards.
Pharmacokinetic Sample Handling Instructions were removed to avoid duplication of instructions that were already present in a separate Laboratory Manual. |
||
19 Aug 2008 |
Subjects who remained on treatment following disease progression were no longer required to undergo radiological evaluations for the purpose of tumor response assessment.
Describe changes to the 20mg tablet formulation and add the 40mg tablet formulation.
Background safety data was updated. |
||
30 Jan 2009 |
Subjects who had disease progression while receiving study drug were allowed to remain on treatment if the investigator and sponsor felt that the subject would benefit. |
||
05 Jun 2009 |
Subjects were required to undergo a full urinalysis, rather than dipstick.
Additionally, the frequency of urinalysis, chemistry, and electrolyte panels was increased to every 2 weeks instead of at the beginning of each 4-week cycle. |
||
02 Dec 2010 |
Clarified that Day 15 laboratory assessments were not required after 6 cycles of treatment if the subject continued to receive clinical benefit from treatment and there were no clinically significant laboratory abnormalities. |
||
15 Jul 2011 |
The purpose of Amendment 6, a global amendment, was to increase liver function test monitoring and include a dose modification table for AST, ALT and bilirubin in the protocol. |
||
04 Dec 2012 |
The purpose of Amendment 7, a global amendment, was to allow for less frequent imaging procedures and laboratory assessment for patients who have been on treatment for more than 2 years (24 cycles). |
||
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. | |||
| "99999" entered in the form stands for "Not Applicable". | |||
