Renal Cell Carcinoma
Conditions
Keywords
temsirolimus, renal cell carcinoma, kidney cancer, urogenital cancer
Brief summary
Primary objective: Comparison of independently assessed progression free survival (PFS) in subjects administered Bevacizumab + Temsirolimus vs. those administered Bevacizumab + Interferon-Alfa. Secondary objectives: safety, Investigator assessed PFS, objective response rate (independently assessed), and overall survival.
Interventions
DRUGTemsirolimus
Temsirolimus 25 mg IV weekly
DRUGBevacizumab
Bevacizumab 10 mg/kg intravenous (IV) q8wks
DRUGInterferon-Alfa 9MU
Interferon-Alfa 9MU SC TIW
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically and/or cytologically confirmed to have advanced renal cell carcinoma (RCC) * Majority component of conventional clear-cell type is mandatory * At least 1 measurable lesion (per RECIST)
Exclusion criteria
* Prior systemic treatment for RCC * Evidence of current or prior central nervous system (CNS) metastases * Cardiovascular disease * Pregnant or nursing women * Additional criteria applies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS): Independent-Assessment | Baseline until disease progression, initiation of new anticancer treatment, or death, assessed every 8 weeks (up to cut-off date: 19 April 2012) | PFS was defined as the interval from the date of randomization until the earlier date of progression or death. Progression was assessed by independent imaging reviewers using Response Evaluation Criteria in Solid Tumors (RECIST) criteria which is 20% increase in sum of longest diameter of target lesions from nadir (the lowest blood counts); measurable increase in non-target lesion; appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS): Investigator-Assessment | Baseline until disease progression, initiation of new anticancer treatment, or death, assessed every 8 weeks (up to cut-off date: 19 April 2012) | PFS was defined as the interval from the date of randomization until the earlier date of progression or death. Progression was assessed by investigator imaging reviewers using RECIST criteria which is 20% increase in sum of longest diameter of target lesions from nadir (the lowest blood counts); measurable increase in non-target lesion; appearance of new lesions. |
| Percentage of Participants With Objective Response (Complete Response/Partial Response): Independent-Assessment | Baseline until disease progression, initiation of new anticancer treatment, or death, assessed every 8 weeks (up to cut-off date: 19 April 2012) | Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and/or non target). PR were those with at least 30% decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent. |
| Overall Survival (OS) | Baseline until death due to any cause, assessed every 8 weeks (up to cut-off date: 19 April 2012) | OS was defined as the time from randomization to death due to any cause, censored at the last date known alive. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death). |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, Colombia, Czechia, France, Germany, Hong Kong, Hungary, India, Italy, Malaysia, Mexico, Netherlands, Poland, Portugal, Russia, Serbia, Singapore, Slovakia, South Africa, South Korea, Spain, Taiwan, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Approximately 800 participants enrolled in this study at 200 sites.
Pre-assignment details
Participants were randomized in a 1:1 ratio, stratified by prior nephrectomy status (yes/no) and Memorial Sloan Kettering Cancer Center (MSKCC) risk factors (good/intermediate/poor), and received either the combination treatment of Temisirolimus + Bevacizumab (Temsr+Bev) or Interferon-alfa + Bevacizumab (IFN+Bev).
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab+Temsirolimus Bevacizumab 10 milligram per kilogram (mg/kg) intravenous infusion over 90 minutes, 60 minutes or 30 minutes depending on the participant's tolerability every other week along with temsirolimus 25 mg intravenous infusion over at least 30 minutes once a week. Treatment was continued until disease progression, unacceptable toxicities, withdrawal of consent, or death. | 400 |
| Bevacizumab+ Interferon-Alfa Bevacizumab 10 mg/kg intravenous infusion over 90 minutes, 60 minutes or 30 minutes depending on the participant's tolerability every other week along with interferon-alfa (IFN) 9 million units (MU) subcutaneous injection every 3 times a week. Treatment was continued until disease progression, unacceptable toxicities, withdrawal of consent, or death. | 391 |
| Total | 791 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 263 | 239 |
| Overall Study | Discontinuation of study by Sponsor | 70 | 76 |
| Overall Study | Lost to Follow-up | 24 | 19 |
| Overall Study | Other reason | 5 | 12 |
| Overall Study | subject request | 38 | 45 |
Baseline characteristics
| Characteristic | Bevacizumab+Temsirolimus | Bevacizumab+ Interferon-Alfa | Total |
|---|---|---|---|
| Age, Continuous | 58.6 years STANDARD_DEVIATION 10.1 | 58.2 years STANDARD_DEVIATION 10.4 | 58.4 years STANDARD_DEVIATION 10.2 |
| Sex: Female, Male Female | 114 Participants | 121 Participants | 235 Participants |
| Sex: Female, Male Male | 286 Participants | 270 Participants | 556 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 383 / 393 | 378 / 391 |
| serious Total, serious adverse events | 184 / 393 | 158 / 391 |
Outcome results
Primary
Progression-Free Survival (PFS): Independent-Assessment
PFS was defined as the interval from the date of randomization until the earlier date of progression or death. Progression was assessed by independent imaging reviewers using Response Evaluation Criteria in Solid Tumors (RECIST) criteria which is 20% increase in sum of longest diameter of target lesions from nadir (the lowest blood counts); measurable increase in non-target lesion; appearance of new lesions.
Time frame: Baseline until disease progression, initiation of new anticancer treatment, or death, assessed every 8 weeks (up to cut-off date: 19 April 2012)
Population: Intent-to-treat (ITT) population included all participants who were randomized to the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab+Temsirolimus | Progression-Free Survival (PFS): Independent-Assessment | 9.1 months |
| Bevacizumab+ Interferon-Alfa | Progression-Free Survival (PFS): Independent-Assessment | 9.3 months |
Comparison: P value was based on 1-sided stratified log-rank test (stratification factors: prior nephrectomy \[yes/no\] and Memorial Sloan Kettering Cancer Center \[MSKCC\] risk factors \[good/intermediate/poor\] at time of randomization). The hazard ratio and corresponding 95 percent (%) confidence interval (CI) from the stratified cox proportional hazard model were also presented.p-value: 0.895% CI: [0.9, 1.3]Log Rank
Secondary
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause, censored at the last date known alive. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).
Time frame: Baseline until death due to any cause, assessed every 8 weeks (up to cut-off date: 19 April 2012)
Population: ITT population included all participants who were randomized to the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab+Temsirolimus | Overall Survival (OS) | 25.8 months |
| Bevacizumab+ Interferon-Alfa | Overall Survival (OS) | 25.5 months |
Comparison: P value was based on 1-sided stratified log-rank test (stratification factors: prior nephrectomy \[yes/no\] and MSKCC risk factors \[good/intermediate/poor\] at time of randomization). The hazard ratio and corresponding 95% CI from the stratified cox proportional hazard model were also presented.p-value: 0.695% CI: [0.9, 1.3]Log Rank
Secondary
Percentage of Participants With Objective Response (Complete Response/Partial Response): Independent-Assessment
Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and/or non target). PR were those with at least 30% decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent.
Time frame: Baseline until disease progression, initiation of new anticancer treatment, or death, assessed every 8 weeks (up to cut-off date: 19 April 2012)
Population: ITT population included all participants who were randomized to the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab+Temsirolimus | Percentage of Participants With Objective Response (Complete Response/Partial Response): Independent-Assessment | 27.0 percentage of participants |
| Bevacizumab+ Interferon-Alfa | Percentage of Participants With Objective Response (Complete Response/Partial Response): Independent-Assessment | 27.4 percentage of participants |
Comparison: P-value (2-sided), risk ratio and associated 95% CI were based on Cochran-Mantel-Haenszel test stratified by prior nephrectomy and MSKCC risk group as randomized.p-value: 195% CI: [0.8, 1.3]Cochran-Mantel-Haenszel
Secondary
Progression-Free Survival (PFS): Investigator-Assessment
PFS was defined as the interval from the date of randomization until the earlier date of progression or death. Progression was assessed by investigator imaging reviewers using RECIST criteria which is 20% increase in sum of longest diameter of target lesions from nadir (the lowest blood counts); measurable increase in non-target lesion; appearance of new lesions.
Time frame: Baseline until disease progression, initiation of new anticancer treatment, or death, assessed every 8 weeks (up to cut-off date: 19 April 2012)
Population: ITT population included all participants who were randomized to the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab+Temsirolimus | Progression-Free Survival (PFS): Investigator-Assessment | 9.1 months |
| Bevacizumab+ Interferon-Alfa | Progression-Free Survival (PFS): Investigator-Assessment | 10.8 months |
Comparison: P-value was based on 1-sided stratified log-rank test (stratification factors: prior nephrectomy \[yes/no\] and MSKCC risk factors \[good/intermediate/poor\] at time of randomization). The hazard ratio and corresponding 95% CI from the stratified cox proportional hazard model were also presented.p-value: 0.995% CI: [1, 1.4]Log Rank