Metastatic Renal Cell Carcinoma (mRCC)
Conditions
Keywords
Kidney cancer, mRCC, metastic renal cell carcinoma, everolimus, sunitinib, pazopanib
Brief summary
Patients with metastatic renal cell carcinoma (mRCC) who failed first-line therapy with sunitinib or pazopanib was treated with everolimus. Efficacy and safety of everolimus was evaluated in these patients.
Interventions
DRUGEverolimus (RAD001)
Everolimus was used as commercially available formulated tablets of 10 mg strength
Sponsors
Novartis Pharmaceuticals
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
* Patients with advanced renal cell carcinoma of a histological or cytological confirmation of clear cell renal carcinoma. * Progression during or after a treatment with sunitinib or pazopanib given in a 1st line treatment situation for mRCC. * Patients scheduled for treatment with everolimus. * Patients with at least one measurable lesion at baseline as per RECIST v1.1.
Exclusion criteria
* Patients who have received \>1 prior systemic treatment for their metastatic RCC. Prior systemic treatment in an adjuvant setting is allowed. * Patients who have previously received systemic mTOR inhibitors (e.g. sirolimus, temsirolimus, everolimus). * Patients who are using other investigational agents or who had received investigational drugs ≤ 2 weeks prior to study treatment start. * Patients unwilling or unable to comply with the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Progression-free Patients by Month 6 | Month 6 | Percentage of progression-free patients by month 6 after starting everolimus treatment. For the purpose of the binomial design of the study, a patient being 'progression-free' will be defined as a patient without disease progression by month 6 whereas a subject with progressive disease by month 6 will not be counted as 'progression-free'. The primary variable was derived from radiologic tumor assessments according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1.) Disease progression was either 1) a 20% increase in the sum of the longest diameter of all target lesions, taking as reference the smallest sum of the longest diameters of all target lesions recorded at or after baseline (minimum absolute increase 5 mm in sum) or 2) the appearance of a new lesion or 3) the unequivocal progression of non-target lesions overall. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Overall Response Rate (ORR) Treated With Everolimus After Failure of First-line Sunitinib or Pazopanib Therapy at Month 6 | Month 6 | Overall response rate (ORR) is the Percentage of patients with a best overall response of complete response (CR) or partial response (PR) by month 6. ORR was assessed according to RECIST 1.1 criteria. Partial response (PR) required at least a 30% decrease in the sum of the longest diameters of all target lesions, taking as reference the baseline sum of the longest diameters. Complete response (CR) required a disappearance of all target and non-target lesions. |
| Progression-Free Survival (PFS) as the Time Interval Between First Intake of Everolimus and First Documented Disease Progression or Death Due to Any Cause at 24 Months | 24 months | Progression-free survival (PFS) is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient did not have an event, progression-free survival was censored at the date of last adequate tumor assessment |
| Overall Survival (OS) of Patients Treated With Everolimus After Failure of First-line Sunitinib or Pazopanib Therapy up to 48 Months | 48 months | Overall survival (OS) was defined as the time from date of start of treatment to date of death due to any cause. If a patient was not known to have died, survival will be censored at the date of last contact. |
| Duration of Response (DOR) in Patients Treated With Everolimus After Failure of First-line Sunitinib or Pazopanib Therapy up to 48 Months | 48 months | The duration of overall response (DOR) was defined as the time from the first occurrence of a confirmed Complete Response (CR) or Partial Response (PR) (as per investigator assessment according to RECIST 1.1) until the date of the first documented disease progression or death due to underlying cancer. If a patient did not have an event or received any further anticancer therapy, duration of overall response was censored at the date of last adequate tumor assessment. Duration of response was displayed only for patients whose best overall response was CR or PR. As none of the patients showed any response (CR or PR), DOR could not be calculated |
Countries
Germany
Participant flow
Pre-assignment details
Single arm study of everolimus broken down into 2 subgroups for analyses and safety based on failed 1st line therapy (sunitinib or pazopanib) prior to starting study.
Participants by arm
| Arm | Count |
|---|---|
| 1st Line SUN Patients that failed 1st line therapy Sunitinib (SUN) prior to starting study. Patients were on Everolimus 10 mg orally once daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawn consent. | 12 |
| 1st Line PAZ Patients that failed 1st line therapy Pazopanib (PAZ) prior to starting study. Patients were on Everolimus 10 mg orally once daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawn consent. | 13 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 7 | 8 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | New Cancer Therapy | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | 1st Line SUN | 1st Line PAZ | Total |
|---|---|---|---|
| Age, Continuous | 67.6 years STANDARD_DEVIATION 6.3 | 71.3 years STANDARD_DEVIATION 6 | 69.2 years STANDARD_DEVIATION 6.3 |
| Sex: Female, Male Female | 6 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 11 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 15 / 16 | 13 / 13 | 28 / 29 |
| serious Total, serious adverse events | 6 / 16 | 8 / 13 | 14 / 29 |
Outcome results
Primary
Percentage of Progression-free Patients by Month 6
Percentage of progression-free patients by month 6 after starting everolimus treatment. For the purpose of the binomial design of the study, a patient being 'progression-free' will be defined as a patient without disease progression by month 6 whereas a subject with progressive disease by month 6 will not be counted as 'progression-free'. The primary variable was derived from radiologic tumor assessments according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1.) Disease progression was either 1) a 20% increase in the sum of the longest diameter of all target lesions, taking as reference the smallest sum of the longest diameters of all target lesions recorded at or after baseline (minimum absolute increase 5 mm in sum) or 2) the appearance of a new lesion or 3) the unequivocal progression of non-target lesions overall.
Time frame: Month 6
Population: Full Analysis Set (FAS) consisted of all patients who received at least one dose of everolimus.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1st Line SUN | Percentage of Progression-free Patients by Month 6 | 8.3 Percentage of participants |
| 1st Line PAZ | Percentage of Progression-free Patients by Month 6 | 46.2 Percentage of participants |
Secondary
Duration of Response (DOR) in Patients Treated With Everolimus After Failure of First-line Sunitinib or Pazopanib Therapy up to 48 Months
The duration of overall response (DOR) was defined as the time from the first occurrence of a confirmed Complete Response (CR) or Partial Response (PR) (as per investigator assessment according to RECIST 1.1) until the date of the first documented disease progression or death due to underlying cancer. If a patient did not have an event or received any further anticancer therapy, duration of overall response was censored at the date of last adequate tumor assessment. Duration of response was displayed only for patients whose best overall response was CR or PR. As none of the patients showed any response (CR or PR), DOR could not be calculated
Time frame: 48 months
Population: Duration of response was displayed only for patients whose best overall response was CR or PR. As none of the patients showed any response (CR or PR), DOR could not be calculated
Secondary
Overall Survival (OS) of Patients Treated With Everolimus After Failure of First-line Sunitinib or Pazopanib Therapy up to 48 Months
Overall survival (OS) was defined as the time from date of start of treatment to date of death due to any cause. If a patient was not known to have died, survival will be censored at the date of last contact.
Time frame: 48 months
Population: Full Analysis Set (FAS) consisted of all patients who received at least one dose of everolimus.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1st Line SUN | Overall Survival (OS) of Patients Treated With Everolimus After Failure of First-line Sunitinib or Pazopanib Therapy up to 48 Months | 14.8 months |
| 1st Line PAZ | Overall Survival (OS) of Patients Treated With Everolimus After Failure of First-line Sunitinib or Pazopanib Therapy up to 48 Months | 20.4 months |
Secondary
Percentage of Patients With Overall Response Rate (ORR) Treated With Everolimus After Failure of First-line Sunitinib or Pazopanib Therapy at Month 6
Overall response rate (ORR) is the Percentage of patients with a best overall response of complete response (CR) or partial response (PR) by month 6. ORR was assessed according to RECIST 1.1 criteria. Partial response (PR) required at least a 30% decrease in the sum of the longest diameters of all target lesions, taking as reference the baseline sum of the longest diameters. Complete response (CR) required a disappearance of all target and non-target lesions.
Time frame: Month 6
Population: Full Analysis Set (FAS) consisted of all patients who received at least one dose of everolimus.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1st Line SUN | Percentage of Patients With Overall Response Rate (ORR) Treated With Everolimus After Failure of First-line Sunitinib or Pazopanib Therapy at Month 6 | 0.0 percentage of participants |
| 1st Line PAZ | Percentage of Patients With Overall Response Rate (ORR) Treated With Everolimus After Failure of First-line Sunitinib or Pazopanib Therapy at Month 6 | 0.0 percentage of participants |
Secondary
Progression-Free Survival (PFS) as the Time Interval Between First Intake of Everolimus and First Documented Disease Progression or Death Due to Any Cause at 24 Months
Progression-free survival (PFS) is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient did not have an event, progression-free survival was censored at the date of last adequate tumor assessment
Time frame: 24 months
Population: Full Analysis Set (FAS) consisted of all patients who received at least one dose of everolimus.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1st Line SUN | Progression-Free Survival (PFS) as the Time Interval Between First Intake of Everolimus and First Documented Disease Progression or Death Due to Any Cause at 24 Months | 2.8 months |
| 1st Line PAZ | Progression-Free Survival (PFS) as the Time Interval Between First Intake of Everolimus and First Documented Disease Progression or Death Due to Any Cause at 24 Months | 8.0 months |