Kidney Cancer
Conditions
Keywords
clear cell renal cell carcinoma, recurrent renal cell cancer, stage IV renal cell cancer
Brief summary
RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well sorafenib works in treating patients with metastatic kidney cancer that has not responded to sunitinib or bevacizumab.
Detailed description
OBJECTIVES: Primary * To determine the tumor burden reduction rate in patients with sunitinib malate- or bevacizumab-refractory, metastatic clear cell renal cell carcinoma treated with sorafenib tosylate. Secondary * To determine the safety of sorafenib tosylate in these patients. * To record the duration of tumor reduction, time to disease progression, and overall survival of patients treated with sorafenib tosylate. OUTLINE: Patients receive oral sorafenib tosylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions
DRUGsorafenib tosylate
Sorafenib (BAY 43-9006) is an oral multi-kinase inhibitor targeting both tumor cells and the tumor vasculature. Patients with metastatic RCC meeting eligibility criteria will receive 400 mg BID of sorafenib in a single-arm phase II study. Treatment will be administered on an outpatient basis.
Sponsors
National Cancer Institute (NCI)
Case Comprehensive Cancer Center
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
DISEASE CHARACTERISTICS: * Histologically confirmed renal cell carcinoma with a component of clear cell histology * Metastatic disease * Disease progression, as defined by RECIST criteria, after prior treatment with sunitinib malate or bevacizumab * Patients must have received ≥ 1 course (4 weeks) of sunitinib malate or ≥ 2 doses of bevacizumab AND have RECIST-defined objective progression during or within 4 months after completing treatment with sunitinib malate or bevacizumab * Measurable disease by RECIST criteria * CNS metastases allowed provided patient has undergone prior surgery and/or radiotherapy AND has no evidence of further CNS disease progression by CT scan or MRI ≥ 2 weeks after treatment of CNS metastases PATIENT CHARACTERISTICS: * ECOG performance status (PS) 0-1 or Karnofsky PS 70-100% * WBC ≥ 3,000/μL * Absolute neutrophil count ≥ 1,500/μL * Platelet count ≥ 75,000/μL * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST/ALT ≤ 2.5 times ULN * Creatinine ≤ 2.0 times ULN * Negative pregnancy test * No significant cardiovascular disease, including any of the following: * Congestive heart failure (New York Heart Association class III-IV heart disease) * Active angina pectoris requiring nitrate therapy * Uncontrolled dysrhythmias * Cardiovascular event within the past 6 months (e.g., transient ischemic attack/cerebrovascular accident, myocardial infarction, or vascular surgery) PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 2 weeks since prior systemic therapy, radiotherapy, or major surgery and recovered * No prior sorafenib tosylate * No other concurrent investigational agents * No other concurrent anticancer therapy * No concurrent prophylactic growth factors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Burden Reduction Rate (TBRR) | at 8 weeks (2cycles of treatment) | The primary endpoint of the study is defined as the percentage of patients who experience larger than or equal to 5% reduction in tumor burden as measured by RECIST-defined target lesions without progression of non-target lesions or the appearance of any new lesions, confirmed at least 4 weeks after first documentation. RECIST criteria will be used for the purpose of designating target lesions, calculating total tumor burden (the sum of the unidimensional measurement of target lesions) and defining disease progression.Additional RECIST-defined partial or complete responses will be recorded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | followed until progression or death for approximately 3 years | Overall survival measured in months and summarized using the Kaplan-Meier method. This will be calculated from the date of registration on-study to the dates of documented evidence of progression and death, respectively. |
| Time to Progression | followed to progression for approximately 3 years | Time to objective progression will be measured from the start of treatment until the criteria for RECIST-defined progression are met, taking as reference the smallest measurements recorded since the treatment started, including baseline. Progression-free survival measured in months and summarized using the Kaplan-Meier method. |
| Duration of Overall Response (Tumor Burden Reduction) | followed for overall response for approximately 3 years | Measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. |
Countries
United States
Participant flow
Recruitment details
This is a multiple site study. Patients were recruited 2/2006-4/2008 from medical hospitals in Cleveland, Ohio and Dallas, Texas
Participants by arm
| Arm | Count |
|---|---|
| Sorafenib Patients receive Sorafenib 400 mg BID until disease progression or toxicity. Dose may be escalated to 600mg and 800 mg BID after the 8 week disease reassessment. | 49 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Sorafenib |
|---|---|
| Age, Continuous | 63.2 years STANDARD_DEVIATION 8.1 |
| Region of Enrollment United States | 49 participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 41 / 47 |
| serious Total, serious adverse events | 4 / 47 |
Outcome results
Primary
Tumor Burden Reduction Rate (TBRR)
The primary endpoint of the study is defined as the percentage of patients who experience larger than or equal to 5% reduction in tumor burden as measured by RECIST-defined target lesions without progression of non-target lesions or the appearance of any new lesions, confirmed at least 4 weeks after first documentation. RECIST criteria will be used for the purpose of designating target lesions, calculating total tumor burden (the sum of the unidimensional measurement of target lesions) and defining disease progression.Additional RECIST-defined partial or complete responses will be recorded.
Time frame: at 8 weeks (2cycles of treatment)
Population: All patients who started treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sorafenib | Tumor Burden Reduction Rate (TBRR) | Achieved at least 5% tumor reduction | 30 percentage of patients |
| Sorafenib | Tumor Burden Reduction Rate (TBRR) | Did not achieve at least 5% tumor reduction | 70 percentage of patients |
Secondary
Duration of Overall Response (Tumor Burden Reduction)
Measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented.
Time frame: followed for overall response for approximately 3 years
Population: Patients who achieved at least 5% tumor reduction
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib | Duration of Overall Response (Tumor Burden Reduction) | 7.1 months |
Secondary
Overall Survival
Overall survival measured in months and summarized using the Kaplan-Meier method. This will be calculated from the date of registration on-study to the dates of documented evidence of progression and death, respectively.
Time frame: followed until progression or death for approximately 3 years
Population: All patients who started treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib | Overall Survival | 16 months |
Secondary
Time to Progression
Time to objective progression will be measured from the start of treatment until the criteria for RECIST-defined progression are met, taking as reference the smallest measurements recorded since the treatment started, including baseline. Progression-free survival measured in months and summarized using the Kaplan-Meier method.
Time frame: followed to progression for approximately 3 years
Population: All patients who started treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib | Time to Progression | 4.4 months |