Carcinoma, Renal Cell
Conditions
Keywords
Renal Cell Carcinoma
Brief summary
This is a uncontrolled, open-label, non-randomized Phase II study of oral BAY73-4506 to evaluate the response rate of BAY73-4506 in previously untreated patients with metastatic or unresectable renal cell cancer (RCC).
Detailed description
The final analysis of efficacy will be performed after last patient has been treated for at least 6 months. Additional periodic safety and efficacy data reviews will be performed for any patients continuing to receive study drug afterwards.
Interventions
DRUGRegorafenib (Stivarga, BAY73-4506)
Patients will be treated with BAY73-4506 160 mg po qd for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off). Patients will continue treatment with BAY73-4506 until disease progression, intolerable toxicity, or patient refusal to continue with the study or investigator decision to remove the patient from study.
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients \>/= 18 years of age. * Patients, who suffer from unresectable and/or metastatic, measurable predominantly clear cell RCC (renal cell carcinoma histologically) or cytologically documented. * Patients must be previously untreated for advanced disease. Prior palliative radiation therapy is allowed if the target lesion(s) are not included within the radiation field and no more than 30% of the bone marrow is irradiated. * Patients who have at least one uni-dimensional measurable lesion by computed tomography (CT-scan) or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST). * Patients with Intermediate or Low risk per the Motzer score. * Patients who have an Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1. * Adequate bone marrow, renal and hepatic function as assessed by the following laboratory requirements to be conducted within 7 days prior to study drug treatment
Exclusion criteria
* Patients who have received prior systemic treatment regimens for RCC. * Uncontrolled/unstable cardiac disease * Uncontrolled hypertension * Active clinically serious infections (\> Common Terminology Criteria for Adverse Events \[CTCAE\] grade 2 ) * History of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C. * Known history or symptomatic metastatic brain or meningeal tumours * Patients with seizure disorder requiring medication * Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event \>/= CTCAE Grade 3 within 4 weeks of first dose of study. * Pregnant or breast-feeding patients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Tumor Response | 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 | 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. |
| Tumor Response | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Stable Disease (SD) | 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 | 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. |
| Disease Control | 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 | 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. |
| Overall Survival | From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). | 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. |
| Progression-free Survival (PFS) | 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 | 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. |
| Time to Progression (TTP) | 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 | 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. |
| Duration of Response | 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 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (Update) | 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 | 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. |
| Duration of Stable Disease (Update) | 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 | 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. |
| Objective Tumor Response (Update) | 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 | 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. |
| Tumor Response (Update) | 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 | 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. |
| Disease Control (Update) | 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 | 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. |
| Overall Survival (Update) | From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). | 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. |
| Progression-free Survival (Update) | 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 | 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. |
| Time to Progression (Update) | 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 | 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. |
Countries
Finland, France, Germany, Poland, United Kingdom, United States
Participant flow
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 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).
Participants by arm
| Arm | Count |
|---|---|
| Regorafenib (Stivarga, BAY73-4506) Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle | 49 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 14 |
| Overall Study | Death | 2 |
| Overall Study | Disease Progression/Recurrence/Relapse | 24 |
| Overall Study | Noncompliance with study medication | 3 |
| Overall Study | Other Reasons | 3 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Regorafenib (Stivarga, BAY73-4506) |
|---|---|
| Age, Continuous | 62.0 Years |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 | 30 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 1 | 19 Participants |
| Overall Motzer Score Intermediate | 25 Participants |
| Overall Motzer Score Low | 24 Participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 39 / 49 |
| other Total, other adverse events | 48 / 49 |
| serious Total, serious adverse events | 32 / 49 |
Outcome results
Primary
Objective Tumor Response
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.
Time frame: 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
Population: Evaluable for response (Primary analysis population)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regorafenib (Stivarga, BAY73-4506) | Objective Tumor Response | 31.3 Percentage of participants |
Primary
Tumor Response
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.
Time frame: 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
Population: Evaluable for response (Primary analysis population)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Regorafenib (Stivarga, BAY73-4506) | Tumor Response | Complete Response (CR) | 0.0 Percentage of participants |
| Regorafenib (Stivarga, BAY73-4506) | Tumor Response | Partial Response (PR) | 31.3 Percentage of participants |
| Regorafenib (Stivarga, BAY73-4506) | Tumor Response | Stable Disease (SD) | 50.0 Percentage of participants |
| Regorafenib (Stivarga, BAY73-4506) | Tumor Response | Progressive Disease (PD) | 10.4 Percentage of participants |
| Regorafenib (Stivarga, BAY73-4506) | Tumor Response | Not Assessable | 8.3 Percentage of participants |
Secondary
Disease Control
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.
Time frame: 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
Population: Evaluable for response (Primary analysis population)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regorafenib (Stivarga, BAY73-4506) | Disease Control | 62.5 Percentage of participants |
Secondary
Duration of Response
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.
Time frame: 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
Population: Only subjects from ITT population with a response of CR or PR were included in this evaluation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regorafenib (Stivarga, BAY73-4506) | Duration of Response | NA Days |
Secondary
Duration of Stable Disease (SD)
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.
Time frame: 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
Population: Subjects from ITT population who achieved objective response of CR or PR were excluded from this evaluation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regorafenib (Stivarga, BAY73-4506) | Duration of Stable Disease (SD) | 172 Days |
Secondary
Overall Survival
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.
Time frame: From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009).
Population: intention-to-treat (ITT)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regorafenib (Stivarga, BAY73-4506) | Overall Survival | NA Days |
Secondary
Progression-free Survival (PFS)
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.
Time frame: 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
Population: intention-to-treat (ITT)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regorafenib (Stivarga, BAY73-4506) | Progression-free Survival (PFS) | 251 Days |
Secondary
Time to Progression (TTP)
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.
Time frame: 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
Population: intention-to-treat (ITT)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regorafenib (Stivarga, BAY73-4506) | Time to Progression (TTP) | 251 Days |
Other Pre-specified
Disease Control (Update)
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.
Time frame: 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
Population: Evaluable for response (Primary analysis population)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regorafenib (Stivarga, BAY73-4506) | Disease Control (Update) | 62.5 Percentage of participants |
Other Pre-specified
Duration of Response (Update)
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.
Time frame: 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
Population: Only subjects from ITT population with a response of CR or PR were included in this evaluation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regorafenib (Stivarga, BAY73-4506) | Duration of Response (Update) | 428 Days |
Other Pre-specified
Duration of Stable Disease (Update)
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.
Time frame: 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
Population: Subjects from ITT population who achieved objective response of CR or PR were excluded from this evaluation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regorafenib (Stivarga, BAY73-4506) | Duration of Stable Disease (Update) | 119 Days |
Other Pre-specified
Objective Tumor Response (Update)
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.
Time frame: 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
Population: Evaluable for response (Primary analysis population)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regorafenib (Stivarga, BAY73-4506) | Objective Tumor Response (Update) | 39.6 Percentage of participants |
Other Pre-specified
Overall Survival (Update)
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.
Time frame: From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011).
Population: intention-to-treat (ITT)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regorafenib (Stivarga, BAY73-4506) | Overall Survival (Update) | NA Days |
Other Pre-specified
Progression-free Survival (Update)
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.
Time frame: 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
Population: intention-to-treat (ITT)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regorafenib (Stivarga, BAY73-4506) | Progression-free Survival (Update) | 335 Days |
Other Pre-specified
Time to Progression (Update)
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.
Time frame: 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
Population: intention-to-treat (ITT)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regorafenib (Stivarga, BAY73-4506) | Time to Progression (Update) | 335 Days |
Other Pre-specified
Tumor Response (Update)
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.
Time frame: 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
Population: Evaluable for response (Primary analysis population)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Regorafenib (Stivarga, BAY73-4506) | Tumor Response (Update) | Complete Response (CR) | 0.0 Percentage of participants |
| Regorafenib (Stivarga, BAY73-4506) | Tumor Response (Update) | Partial Response (PR) | 39.6 Percentage of participants |
| Regorafenib (Stivarga, BAY73-4506) | Tumor Response (Update) | Stable Disease (SD) | 41.7 Percentage of participants |
| Regorafenib (Stivarga, BAY73-4506) | Tumor Response (Update) | Progressive Disease (PD) | 10.4 Percentage of participants |
| Regorafenib (Stivarga, BAY73-4506) | Tumor Response (Update) | Not Assessable | 8.3 Percentage of participants |