Kidney Neoplasms, Kidney (Renal Cell) Cancer
Conditions
Brief summary
To determine the safety and efficacy of the combination of bevacizumab and everolimus (RAD001) for the treatment of metastatic renal cell cancer
Interventions
DRUGEverolimus
DRUGBevacizumab
Sponsors
Genentech, Inc.
Novartis
Sandy Srinivas
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
* Signed Informed Consent Form * Histologically confirmed metastatic RCC that is predominantly clear cell Measurable disease, as defined by RECIST * Age ≥ 18 years * ECOG performance status of 0 or 1 * No more than 1 prior targeted therapy (eg, sorafenib, sunitinib) (prior cytokine therapy allowed) * No more than 2 prior systemic therapies * Ability and capacity to comply with the study and follow-up procedures General
Exclusion criteria
* Inability to comply with study and/or follow-up procedures * Life expectancy of \< 12 weeks * Inadequate organ function, as evidenced by any of the following at screening: * Absolute neutrophil count (ANC) \< 1500/uL * Platelet count ≤ 100 x 10\^9/L * Total bilirubin ≥ 1.5 x upper limit of normal (ULN) * AST and/or ALT \> 2.5 x ULN for patients without evidence of liver metastases, or 5 x ULN for patients with documented liver metastases * Serum creatinine \> 2.0 mg/dL * Hemoglobin \< 9 g/dL (may be transfused or receive epoetin alfa to maintain or exceed this level) * Active infection or fever \> 38.5°C within 3 days of starting treatment * Women who are pregnant or breast feeding, * Able to conceive and unwilling to practice an effective method of birth control. * History of other malignancies within 5 years prior to Day 1 except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma, squamous-cell carcinoma of the skin, carcinoma in situ of the cervix, early-stage bladder cancer, or low-grade endometrial cancer * Malignancies that have undergone a putative surgical cure (i.e., localized prostate cancer post-prostatectomy) within 5 years prior to Day 1 may be discussed with the Principal Investigator. * Any other medical conditions (including mental illness or substance abuse) deemed by the clinician to be likely to interfere with a patient's ability to provide informed consent, cooperate, or participate in the study, or to interfere with the interpretation of the results. * Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study Disease-Specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | 24 months | Progression-free survival (PFS) per RECIST criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response (OR) Duration | 24 months | — |
| Time-to-Treatment Failure (TTF) | 24 months | — |
| Overall Survival (OS) | 44 months | — |
| Objective Response (OR) | 24 months | Number of subjects with objective response (OR) |
| Total Number of Drug-related SAEs | 24 months | — |
| Treatment Discontinuation Due to Toxicity | 24 months | Number of subjects whose treatment was discontinued due to toxicity |
| Treatment Discontinuation Due to Disease Progression | 24 months | Number of subjects whose treatment was discontinued due to disease progression |
| Number of Subjects With Drug-related SAEs | 24 months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab + RAD001 (Everolimus) Study treatment, consisting of bevacizumab + everolimus, was administered as 28-day cycles
Bevacizumab 10 mg/kg administered by IV infusion every 14 days (dose suspension permitted, dose reduction not permitted)
Everolimus 10 mg daily was administered orally (dose reduction to 5 mg daily and then 5 mg every other day, was permitted as needed for toxicity or tolerability)
Everolimus
Bevacizumab | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Bevacizumab + RAD001 (Everolimus) |
|---|---|
| Age, Continuous | 55 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 6 / 10 |
Outcome results
Primary
Progression-free Survival (PFS)
Progression-free survival (PFS) per RECIST criteria
Time frame: 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + RAD001 (Everolimus) | Progression-free Survival (PFS) | 5.1 months |
Secondary
Number of Subjects With Drug-related SAEs
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + RAD001 (Everolimus) | Number of Subjects With Drug-related SAEs | 3 participants |
Secondary
Objective Response (OR)
Number of subjects with objective response (OR)
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + RAD001 (Everolimus) | Objective Response (OR) | 1 participants |
Secondary
Objective Response (OR) Duration
Time frame: 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + RAD001 (Everolimus) | Objective Response (OR) Duration | 21.7 weeks |
Secondary
Overall Survival (OS)
Time frame: 44 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + RAD001 (Everolimus) | Overall Survival (OS) | 21.0 months |
Secondary
Time-to-Treatment Failure (TTF)
Time frame: 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + RAD001 (Everolimus) | Time-to-Treatment Failure (TTF) | 5.1 months |
Secondary
Total Number of Drug-related SAEs
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + RAD001 (Everolimus) | Total Number of Drug-related SAEs | 4 events |
Secondary
Treatment Discontinuation Due to Disease Progression
Number of subjects whose treatment was discontinued due to disease progression
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + RAD001 (Everolimus) | Treatment Discontinuation Due to Disease Progression | 6 participants |
Secondary
Treatment Discontinuation Due to Toxicity
Number of subjects whose treatment was discontinued due to toxicity
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + RAD001 (Everolimus) | Treatment Discontinuation Due to Toxicity | 4 participants |