Kidney Cancer
Conditions
Brief summary
This study is being done in 2 parts. The first part is to determine the dose of RAD001 that should be used in combination with sorafenib. The second part is using the above determined dose of RAD001 in combination with sorafenib to see how effective these 2 drugs are against advanced kidney cancer. Participants will be asked to keep a pill diary.
Detailed description
The drugs used in this trial are called targeted drugs as they target specific activities that are carried out by cancer cells that make them grow and spread. Sorafenib is an approved drug for the treatment of advanced kidney cancer. RAD001 is an experimental drug that has been used in other research studies with other types of cancer. In this trial, the use of RAD001 and sorafenib together for the treatment of kidney cancer is experimental. In the Phase I portion of this study 13-16 patients will be treated with the same dose of sorafenib and different doses of RAD001. The purpose is to see what is a safe dose of RAD001 when combined with sorafenib in the treatment of kidney cancer. Once this dose of RAD001 is determined, about 65 more patients will be treated to see how effective this combination of drugs is against this kidney cancer. Both of these drugs are taken by mouth. Sorafenib will be taken twice a day. RAD001 is taken by mouth weekly. Patients will be able to continue treatment as long as their disease does not worsen or side effects become intolerable.
Interventions
DRUGSorafenib
Sorafenib
DRUGRAD001
RAD001
Sponsors
Novartis
Bayer
SCRI Development Innovations, LLC
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
* Clinically documented metastatic or unresectable locally recurrent clear cell renal carcinoma * Previous removal of kidney except if the size of the tumor was less than 5 cm or there was extensive liver or bone metastasis * May have had no prior chemotherapy or up to 1 prior treatment regimen with immunotherapy or chemotherapy * Performance status of 0-1 * Measurable disease * Adequate liver, renal, and bone marrow function * Must be able to give written informed consent * Women able to become pregnant must have a negative pregnancy test * Must be 18 or over * Must be able to swallow pills
Exclusion criteria
* Prior treatment with sorafenib or m-TOR inhibitors * History of acute MI within the last 6 months * Active brain metastasis or patients with meningeal metastases * Prior treatment for another cancer in the last 5 years * Prior bleeding problems; coughing up or vomiting blood * Non-healing wounds, ulcer, or long bone fracture * Chronic use of systemic steroids or immunosuppressive agents * Uncontrolled hypertension Please note: There are additional inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) of Patients Treated at MTD/Phase II Dose Level | 18 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response Rate (ORR) = Percentage of Patients Who Experience an Objective Response (CR+ PR) to Treatment. In oncology, this outcome measure is reported for all patients treated at the same dose level and is not separated into Phase I and Phase II. The phase I and phase II results are not separated out as the timing of their enrollment (early in phase 1 or later phase II) is not relevant to the outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival for Patients Treated at MTD/Phase II Dose Level | 18 months | Progression is Defined Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% Increase in the Sum of the Longest Diameter of Target Lesions, or a Measurable Increase in a Non-target Lesion, or the Appearance of New Lesions. Progression-free survival was defined as the interval from the date of study entry until the date of tumor progression or death for the patients treated at the MTD/Phase II dose level. This outcome measure is reported for all patients treated at the same dose level and is not separated into Phase I and Phase II. The phase I and phase II results are not separated out as the timing of their enrollment (early in phase 1 or later phase II) is not relevant to the outcome measure. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase 1 Dose Level 1 sorafenib 400 mg BID and everolimus 35 mg once weekly | 3 |
| Phase 1 Dose Level -1 Sorafenib 200 mg PO BID, everolimus 35 mg PO once weekly | 6 |
| Phase II 200 mg PO BID and everolimus 35 mg PO once weekly | 69 |
| Total | 78 |
Baseline characteristics
| Characteristic | Phase 1 Dose Level 1 | Phase 1 Dose Level -1 | Phase II | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 5 Participants | 25 Participants | 31 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 1 Participants | 44 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 6 Participants | 52 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 17 Participants | 17 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 6 Participants | 67 Participants | 75 Participants |
| Region of Enrollment United States | 3 participants | 6 participants | 69 participants | 78 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 21 Participants | 24 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 48 Participants | 54 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 | 3 / 3 | 6 / 6 | 69 / 69 |
| serious Total, serious adverse events | 0 / 3 | 0 / 6 | 21 / 69 |
Outcome results
Primary
Overall Response Rate (ORR) of Patients Treated at MTD/Phase II Dose Level
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response Rate (ORR) = Percentage of Patients Who Experience an Objective Response (CR+ PR) to Treatment. In oncology, this outcome measure is reported for all patients treated at the same dose level and is not separated into Phase I and Phase II. The phase I and phase II results are not separated out as the timing of their enrollment (early in phase 1 or later phase II) is not relevant to the outcome measure.
Time frame: 18 months
Population: Pts who received MTD dose also called Phase II dose (Sorafenib 200 mg PO BID, everolimus 35 mg). The 6 phase I pts and 69 phase II pts treated at this dose level are combined to evaluate the efficacy of the MTD/phase II dose. The Ph I and Ph II results are not separated out as the timing of their enrollment (early in Ph 1 or later Ph II) is not relevant to the outcome measure. 3 Ph I patients who were not treated at the MTD are excluded as this Outcome Measure is for MTD/Phase II dose level only
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RAD001 and Sorafenib | Overall Response Rate (ORR) of Patients Treated at MTD/Phase II Dose Level | 13 percentage of evaluable patients |
Secondary
Progression-Free Survival for Patients Treated at MTD/Phase II Dose Level
Progression is Defined Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% Increase in the Sum of the Longest Diameter of Target Lesions, or a Measurable Increase in a Non-target Lesion, or the Appearance of New Lesions. Progression-free survival was defined as the interval from the date of study entry until the date of tumor progression or death for the patients treated at the MTD/Phase II dose level. This outcome measure is reported for all patients treated at the same dose level and is not separated into Phase I and Phase II. The phase I and phase II results are not separated out as the timing of their enrollment (early in phase 1 or later phase II) is not relevant to the outcome measure.
Time frame: 18 months
Population: Pts who received MTD dose also called Phase II dose (Sorafenib 200 mg PO BID, everolimus 35 mg). The 6 phase I pts and 69 phase II pts treated at this dose level are combined to evaluate the efficacy of the MTD/phase II dose. The Ph I and Ph II results are not separated out as the timing of their enrollment (early in Ph 1 or later Ph II) is not relevant to the outcome measure. 3 Ph I patients who were not treated at the MTD are excluded as this Outcome Measure is for MTD/Phase II dose level only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RAD001 and Sorafenib | Progression-Free Survival for Patients Treated at MTD/Phase II Dose Level | 5.45 Months |