Adenocarcinoma, Carcinoma, Non Clear Cell Renal Carcinoma, Papillary Cell Renal Carcinoma, Renal Cell
Conditions
Keywords
renal cell carcinoma, non clear cell carcinoma, papillary cell renal carcinoma, adults, everolimus
Brief summary
To evaluate the preliminary efficacy and safety of RAD001 as monotherapy for first-line treatment of patients with metastatic papillary carcinoma of the kidney.
Interventions
DRUGRAD001
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
1. ≥ 18 years old. 2. Patients with metastatic papillary renal cell carcinoma, type I or II. 3. Patients with at least one measurable lesion. 4. Patients with an ECOG Performance Status ≤1. 5. Adequate bone marrow function. 6. Adequate liver function. 7. Adequate renal function. 8. Adequate lipid profile.
Exclusion criteria
1. Patients who had radiation therapy within 28 days prior to start of study. 2. Patients who have received prior systemic treatment for their metastatic RCC. 3. Patients who received prior therapy with VEGF pathway inhibitor. 4. Patients who have previously received systemic mTOR inhibitors. 5. Patients with a known hypersensitivity everolimus or other rapamycins or to its excipients. 6. Patients with uncontrolled central nervous system (CNS) metastases. 7. Patients receiving chronic systemic treatment with corticosteroids or another immunosuppressive agent. 8. Patients with a known history of HIV seropositivity. 9. Patients with autoimmune hepatitis. 10. Patients with an active, bleeding diathesis. 11. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study. 12. Patients who have a history of another primary malignancy and off treatment ≤ 3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of the uterine cervix. 13. Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. 14. Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to study treatment start. 15. Patients unwilling to or unable to comply with the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate Efficacy of RAD001 as Monotherapy for the Treatment of Papillary Renal Cancer. Efficacy is Defined as the Percentage of Patients Progression-free at 6 Months. | 6 mos | PFSR at 6 months based on central review |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (SD + PR + CR) | 6 mos | DCR was defined as the proportion of patients with a best overall response of CR, PR or SD and ORR as the percentage of patients with CR or PR |
| Objective Response Rate | End of trial | ORR is defined as the proportion of patients with tumor size reduction of a predefined amount and for a minimum time period. Response duration usually is measured from the time of initial response until documented tumor progression |
| Duration of Response | End of trial | The DOR analysis applied only to patients whose overall response was CR or PR and was defined as the time from onset of response (CR/PR) to progression or death from any cause. |
| Median Progression Free Survival | End of trial | PFS was defined as the time from first study drug administration to objective tumor progression or death from any cause. |
| Incidence of Adverse Events, Serious Adverse Events, and Death. | End of trial | — |
Countries
Belgium, France, Germany, Italy, Poland, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RAD001 10 mg two 5 mg tablets of everolimus orally, once daily | 92 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 20 |
| Overall Study | Death | 9 |
| Overall Study | Disease progression | 55 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Missing | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | RAD001 10 mg |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 16 Participants |
| Age, Categorical Between 18 and 65 years | 76 Participants |
| Age, Continuous | 59.9 years STANDARD_DEVIATION 14.9 |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 90 / 92 |
| serious Total, serious adverse events | 43 / 92 |
Outcome results
Primary
To Evaluate Efficacy of RAD001 as Monotherapy for the Treatment of Papillary Renal Cancer. Efficacy is Defined as the Percentage of Patients Progression-free at 6 Months.
PFSR at 6 months based on central review
Time frame: 6 mos
Population: PP, PPFF, ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RAD001 | To Evaluate Efficacy of RAD001 as Monotherapy for the Treatment of Papillary Renal Cancer. Efficacy is Defined as the Percentage of Patients Progression-free at 6 Months. | (PPFF Set, N=44) | 34.1 % participants |
| RAD001 | To Evaluate Efficacy of RAD001 as Monotherapy for the Treatment of Papillary Renal Cancer. Efficacy is Defined as the Percentage of Patients Progression-free at 6 Months. | (PPSet, N=66) | 33.3 % participants |
| RAD001 | To Evaluate Efficacy of RAD001 as Monotherapy for the Treatment of Papillary Renal Cancer. Efficacy is Defined as the Percentage of Patients Progression-free at 6 Months. | (ITT Set, N=86) | 32.6 % participants |
Secondary
Disease Control Rate (SD + PR + CR)
DCR was defined as the proportion of patients with a best overall response of CR, PR or SD and ORR as the percentage of patients with CR or PR
Time frame: 6 mos
Population: PP,ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RAD001 | Disease Control Rate (SD + PR + CR) | PP set | 65.2 % Participants |
| RAD001 | Disease Control Rate (SD + PR + CR) | ITT set | 65.1 % Participants |
Secondary
Duration of Response
The DOR analysis applied only to patients whose overall response was CR or PR and was defined as the time from onset of response (CR/PR) to progression or death from any cause.
Time frame: End of trial
Population: In the final analysis, for central review, the DOR could not be calculated as only 1 patient in the PP and ITT sets met the criteria
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| RAD001 | Duration of Response | local review PP set | 169 days |
| RAD001 | Duration of Response | local review ITT set | 226 days |
Secondary
Incidence of Adverse Events, Serious Adverse Events, and Death.
Time frame: End of trial
Population: Safety Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RAD001 | Incidence of Adverse Events, Serious Adverse Events, and Death. | Patients with any AE | 100 % participants |
| RAD001 | Incidence of Adverse Events, Serious Adverse Events, and Death. | AE with suspected relation to study drug | 97.83 % participants |
| RAD001 | Incidence of Adverse Events, Serious Adverse Events, and Death. | AE leading to dose adjustment or interruption | 53.26 % participants |
| RAD001 | Incidence of Adverse Events, Serious Adverse Events, and Death. | AE leading to permanent discontinuation | 27.17 % participants |
| RAD001 | Incidence of Adverse Events, Serious Adverse Events, and Death. | AE requiring concomitant medication | 90.22 % participants |
| RAD001 | Incidence of Adverse Events, Serious Adverse Events, and Death. | Patients with serious adverse event (SAE) | 46.74 % participants |
| RAD001 | Incidence of Adverse Events, Serious Adverse Events, and Death. | SAE suspected relation to study drug | 23.91 % participants |
| RAD001 | Incidence of Adverse Events, Serious Adverse Events, and Death. | SAE leading to permanent discontinuation | 10.87 % participants |
| RAD001 | Incidence of Adverse Events, Serious Adverse Events, and Death. | Patients died | 10.87 % participants |
Secondary
Median Progression Free Survival
PFS was defined as the time from first study drug administration to objective tumor progression or death from any cause.
Time frame: End of trial
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| RAD001 | Median Progression Free Survival | PP set | 118 days |
| RAD001 | Median Progression Free Survival | ITT set | 113 days |
Secondary
Objective Response Rate
ORR is defined as the proportion of patients with tumor size reduction of a predefined amount and for a minimum time period. Response duration usually is measured from the time of initial response until documented tumor progression
Time frame: End of trial
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RAD001 | Objective Response Rate | PP Set | 1.5 % participants |
| RAD001 | Objective Response Rate | ITT Set | 1.2 % participants |