Kidney Cancer
Conditions
Keywords
stage III renal cell cancer, stage IV renal cell cancer, clear cell renal cell carcinoma, recurrent renal cell cancer
Brief summary
RATIONALE: Everolimus and imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Everolimus may also block blood flow to the tumor. Giving everolimus together with imatinib mesylate may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving everolimus together with imatinib mesylate works in treating patients with metastatic or unresectable kidney cancer.
Detailed description
OBJECTIVES: Primary * Estimate the proportion of patients with previously treated metastatic or unresectable clear cell carcinoma of the kidney who are progression free (complete response \[CR\], partial response \[PR\], or stable disease \[SD\]) at 3 months after treatment with everolimus and imatinib mesylate. Secondary * Estimate median time to progression in patients treated with this regimen. * Determine the proportion of patients whose best overall response are CR, PR, SD, or progressive disease. * Evaluate the mean and range of the maximum percent reduction in tumor size. * Describe the toxicities of this regimen in these patients. OUTLINE: This is an open-label, multicenter study. Patients receive oral imatinib mesylate and oral everolimus once daily beginning on day 1 and continuing in the absence of disease progression. PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.
Interventions
DRUGEverolimus
2.5 mg by mouth daily
DRUGimatinib mesylate
600 mg by mouth daily
Sponsors
National Cancer Institute (NCI)
OHSU Knight Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed clear cell kidney cancer, meeting 1 of the following criteria: * Measurable metastatic disease * Locally unresectable disease * No history of known brain metastases that have not been adequately treated with radiotherapy and/or surgery * Must have received ≥ 1 prior systemic therapy for metastatic or unresectable renal cell carcinoma PATIENT CHARACTERISTICS: * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Absolute neutrophil count \> 1,500/mm³ * Platelet count \> 100,000/mm³ * Hemoglobin \> 8 g/dL * Bilirubin \< 1.5 times upper limit of normal (ULN) * Serum glutamic oxaloacetic transaminase(SGOT) and Serum glutamic pyruvic transaminase(SGPT) \< 2.5 times ULN * Creatinine \< 1.5 times ULN * No New York Heat Association grade III-IV cardiac disease * No other malignancy within the past 5 years except basal cell skin cancer, cervical carcinoma in situ, or insignificant or inactive disease * No chronic liver disease (i.e., chronic active hepatitis or cirrhosis) * No severe or uncontrolled medical disease * No gastrointestinal disease or impairment that would hinder the absorption of everolimus * No uncontrolled diabetes * No chronic renal disease * No active uncontrolled infection * No congestive heart failure * No myocardial infarction within the past 6 months PRIOR CONCURRENT THERAPY: * See Disease Characteristics * More than 2 weeks since prior major surgery * More than 4 weeks since prior chemotherapy (6 weeks for nitrosourea or mitomycin C) * More than 4 weeks since prior immunotherapy * More than 4 weeks since other prior investigational agents * No prior radiotherapy to \> 25% of bone marrow * No prior treatment with an mammalian target of rapamycin(mTOR) inhibitor * No concurrent therapeutic warfarin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free Survival at 3 Months | 3 months post 1st dose |
| Overall Number of Participants Who Achieve a Response Rate (Complete Response, Partial Response, and Stable Disease) at 3 Months | Up to 4 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Time to Progression | Time to progression | — |
| Number of Subjects That Demonstrated a Reduction in Tumor Measurements. | Up to 4 years | Number of subjects that received at least one post-baseline scan that demonstrated a reduction in sum target lesions per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. |
| Number of Participants With Adverse Events | Duration of study, Up to 4 years | Toxicity assessments will be obtained as follows: Cycle 1: Weeks 1,2,3 Cycle 2: Weeks 6,9 Cycle 3: Weeks 12, 15 Cycle 4: Weeks 18, 21 Cycle 5: Weeks 24, 27 Cycle 6+: Every visit during these cycles Safety assessments will consist of evaluating adverse events and serious adverse events. |
Countries
United States
Participant flow
Recruitment details
Initial recruitment began in Feb 2006 and ended in Dec 2007. 19 patients were put on study during that time frame. These patients came from OHSU oncology clinics or referrals to OHSU.
Pre-assignment details
During the first stage, patients not assessable for progression-free status at 3 months due to study discontinuation for any reason except death or progression were replaced only for purposes of determining continuation to the second stage.A total of 19 patients were enrolled in the first stage 15 evaluable patients and 4 patients who were not.
Participants by arm
| Arm | Count |
|---|---|
| Everolimus and Imatinib Mesylate Everolimus: 2.5 mg daily by mouth
Imatinib Mesylate: 600 mg daily by mouth | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 4 |
Baseline characteristics
| Characteristic | Everolimus and Imatinib Mesylate |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 65 years STANDARD_DEVIATION 7.7459 |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 19 / 19 |
| serious Total, serious adverse events | 10 / 19 |
Outcome results
Primary
Overall Number of Participants Who Achieve a Response Rate (Complete Response, Partial Response, and Stable Disease) at 3 Months
Time frame: Up to 4 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Everolimus and Imatinib Mesylate | Overall Number of Participants Who Achieve a Response Rate (Complete Response, Partial Response, and Stable Disease) at 3 Months | 18 participants |
Primary
Progression-free Survival at 3 Months
Time frame: 3 months post 1st dose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Everolimus and Imatinib Mesylate | Progression-free Survival at 3 Months | 2.9 months |
Secondary
Median Time to Progression
Time frame: Time to progression
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Everolimus and Imatinib Mesylate | Median Time to Progression | 2.9 months |
Secondary
Number of Participants With Adverse Events
Toxicity assessments will be obtained as follows: Cycle 1: Weeks 1,2,3 Cycle 2: Weeks 6,9 Cycle 3: Weeks 12, 15 Cycle 4: Weeks 18, 21 Cycle 5: Weeks 24, 27 Cycle 6+: Every visit during these cycles Safety assessments will consist of evaluating adverse events and serious adverse events.
Time frame: Duration of study, Up to 4 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Everolimus and Imatinib Mesylate | Number of Participants With Adverse Events | 19 participants |
Secondary
Number of Subjects That Demonstrated a Reduction in Tumor Measurements.
Number of subjects that received at least one post-baseline scan that demonstrated a reduction in sum target lesions per Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Time frame: Up to 4 years
Population: 2 subjects were not evaluable. Reduction in target lesion sum did not meet the criteria for Partial Response (PR) for any of the subjects. Partial Response, per RECIST, includes at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Everolimus and Imatinib Mesylate | Number of Subjects That Demonstrated a Reduction in Tumor Measurements. | 5 Participants |