Carcinoma, Renal Cell
Conditions
Keywords
metastatic, renal, cell, carcinoma, cancer
Brief summary
The purpose of this study is to learn if PET scanning can predict the degree of tumor shrinkage with the study drug RAD001 in subjects who have advanced renal cancer.
Interventions
DRUGRAD001
take 2 tablets of RAD001 once a day by mouth (10 mg per day)
Sponsors
Novartis
University of Chicago
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
* Metastatic renal cancer refractory to sorafenib or sunitinib therapy * At least one measurable site of disease according to RECIST criteria that has not been previously irradiated. * 18 years of age or older * Minimum of two weeks since any major surgery, completion of radiation, or completion of all prior standard systemic anticancer therapy and adequately recovered from the acute toxicities of any prior therapy. * World Health Organization (WHO) performance status \<= 2 * Adequate bone marrow function * Adequate liver function * Adequate creatinine clearance * Signed informed consent
Exclusion criteria
* Prior treatment with any investigational drug within the previous 4 weeks * Chronic treatment with systemic steroids or another immunosuppressive agent * Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases * Patients who have a history of another primary malignancy ≤ 3 years, with the exceptions of non-melanoma skin cancer, and carcinoma in situ of uterine cervix * Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study * A known history of HIV seropositivity * Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) * Patients with an active, bleeding diathesis or on oral anti-vitamin K medication * Women who are pregnant or breast feeding, or women/men able to conceive and unwilling to practice an effective method of birth control from enrollment through 6 months following the end of treatment * Patients who have received prior treatment with an mTOR inhibitor. * Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients * History of noncompliance to medical regimens * Patients unwilling to or unable to comply with the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative Tumor Size Change Following 8 Weeks of Therapy. | 8 weeks | The primary objective is to determine whether high SUV uptake on FDG-PET is associated with greater tumor shrinkage. Tumor size is defined as the sum of unidimensional tumor measurements from standard CT imaging calculated according to RECIST criteria. Tumor size is measured at baseline and after eight weeks of therapy. Tumor shrinkage is the relative change (%) in tumor size from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in FDG-PETUptake Following 2 Weeks of Therapy | 2 weeks | The secondary objective was to explore whether an early change in FDG-PET uptake is associated with tumor shrinkage. Change in FDG-PET uptake was calculated using the baseline and 2-week FDG-PET scans. |
Countries
United States
Participant flow
Recruitment details
A total of 60 patients started trial between December, 2007 and June, 2010 at 5 clinical sites. . A total of 63 patients signed consent, (1 withdrew consent, 2 failed screening)
Pre-assignment details
This is a single-arm trial.
Participants by arm
| Arm | Count |
|---|---|
| Everolimus All patients were to receive 10mg everolimus (RAD001) daily. | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Evaluable for Primary Endpoint | Adverse Event | 2 |
| Evaluable for Primary Endpoint | Death | 1 |
| Evaluable for Primary Endpoint | Did not complete 2d CT scan | 3 |
| Evaluable for Primary Endpoint | Lack of Efficacy | 1 |
| Evaluable for Primary Endpoint | Lost to Follow-up | 1 |
| Evaluable for Primary Endpoint | Worsening performance status | 2 |
| Evaluable for Secondary Endpoint | Did not complete 2d FDG-PET scan | 2 |
Baseline characteristics
| Characteristic | Everolimus |
|---|---|
| Age, Continuous | 60 years |
| Average SUVmax High Uptake (avgSUVmax>4) | 40 participants |
| Average SUVmax Low Uptake (avgSUVmax<=4) | 10 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 35 Participants |
| Tumor Type Chromophobe | 4 participants |
| Tumor Type Clear Cell | 36 participants |
| Tumor Type Papillary Cell | 4 participants |
| Tumor Type Unclassified/Other | 6 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 55 / 56 |
| serious Total, serious adverse events | 6 / 56 |
Outcome results
Primary
Relative Tumor Size Change Following 8 Weeks of Therapy.
The primary objective is to determine whether high SUV uptake on FDG-PET is associated with greater tumor shrinkage. Tumor size is defined as the sum of unidimensional tumor measurements from standard CT imaging calculated according to RECIST criteria. Tumor size is measured at baseline and after eight weeks of therapy. Tumor shrinkage is the relative change (%) in tumor size from baseline.
Time frame: 8 weeks
Population: 50 patients were evaluable for response and had a baseline FDG-PET scan.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low Uptake | Relative Tumor Size Change Following 8 Weeks of Therapy. | 1.4 Percent change from baseline |
| High Uptake | Relative Tumor Size Change Following 8 Weeks of Therapy. | -0.57 Percent change from baseline |
Comparison: Relative changes in tumor size were log-transformed to satisfy the normality assumption.p-value: 0.6995% CI: [-9.3, 13.23]t-test, 2 sided
Secondary
Percent Change in FDG-PETUptake Following 2 Weeks of Therapy
The secondary objective was to explore whether an early change in FDG-PET uptake is associated with tumor shrinkage. Change in FDG-PET uptake was calculated using the baseline and 2-week FDG-PET scans.
Time frame: 2 weeks
Population: Patients evaluable for tumor response at 8 weeks who also had both the baseline and 2-week FDG-PET scans.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low Uptake | Percent Change in FDG-PETUptake Following 2 Weeks of Therapy | -29.7 % change in avgSUVmax at 2 weeks |
Comparison: The relationship between early changes in SUV uptake (from baseline to 2 weeks) and tumor size changes (from baseline to 8 weeks) were examined using linear regression models. Tumor size change was log-transformed to satisfy the normality assumption.p-value: 0.01395% CI: [0.00063, 0.004997]Regression, Linear