Kidney Cancer
Conditions
Keywords
clear cell renal cell carcinoma, stage III renal cell cancer, stage IV renal cell cancer, recurrent 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 the side effects and how well sorafenib works in treating patients with metastatic or unresectable kidney cancer.
Detailed description
OBJECTIVES: Primary * Evaluate the safety and toxicity of dose escalating sorafenib tosylate in patients with metastatic or unresectable renal cell carcinoma. Secondary * Determine tumor response in these patients. * Determine time to progression in these patients. * Determine overall survival of these patients. Tertiary * Collect data on angiogenesis inhibition induced by sorafenib tosylate. * Collect data on immunomodulatory effects of sorafenib tosylate. OUTLINE: This is an open-label study. Patients receive oral sorafenib tosylate twice daily on days 1-28. Treatment repeats every 4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients receive escalating doses of sorafenib tosylate (in the absence of grade 3 or 4 dose-limiting toxicity) until a pre-determined dose is reached. Blood and urine samples are collected at baseline and periodically during study for VEGF level determination. Blood samples are analyzed for T4/T8, NK, CD25+, and Fox p3 by flow cytometry. Tumor tissue blocks or unstained slides are obtained for chemistry staining of VEGF.
Interventions
DRUGSorafenib
initial dose of Sorafenib will be administered orally with a dose of 400 mg twice a day, daily.Intrapatient dose escalation will occur providing no dose limiting toxicity (Grade 3 or 4) is observed. Dose level 2 600mg. Dose level 2 800mg
Sponsors
National Cancer Institute (NCI)
Bayer
University of Nebraska
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: Inclusion Criteria: * Histologically or cytologically confirmed renal cell carcinoma (RCC) * Must have a component of conventional clear cell RCC * Predominant clear cell component ≥ 75% * Metastatic or unresectable disease (Measurable disease is defined as any lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan or MRI) * Measurable or nonmeasurable disease, includes any of the following: * Small lesions, longest diameter \< 20 mm by conventional techniques or \< 10 mm by spiral CT scan * Bone lesions * Leptomeningeal disease * Ascites * Pleural/pericardial effusion * Lymphangitis cutis/pulmonitis * Abdominal masses that are not confirmed and followed by imaging techniques * Cystic lesions * Irradiated lesions, unless progression is documented after radiotherapy * Paraffin RCC tissue blocks or unstained slides must be obtained for future chemistry staining of VEGF * Karnofsky performance status 70-100% * Fertile patients must use effective contraception (hormonal and/or barrier method) during and for 3 months after completion of study treatment * Granulocyte count ≥ 1,500/µL * Platelet count ≥ 100,000/µL * AST/ALT ≤ 2.5 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 2.5 times ULN * Serum bilirubin ≤ 1.5 times ULN * Protein ≤ 1+ by urinalysis * Creatinine ≤ 1.5 times ULN * At least 4 weeks since prior major surgery and/or radiotherapy and recovered * Prior palliative radiotherapy for metastatic lesion(s) allowed provided there is at least one measurable and/or evaluable lesion(s) that has not been irradiated * More than 4 weeks since prior and no other concurrent anticancer therapy * Concurrent continuation of bisphosphonates allowed for bone metastases prophylaxis
Exclusion criteria
* Patients with true papillary, sarcomatoid features without any clear cell component, chromophobe, oncocytoma, collecting duct tumors, or transitional cell carcinoma are not eligible * No evidence of CNS metastases * No imaging (MRI or CT scan of the brain) abnormality indicative of CNS metastases within past 42 days * Not pregnant or nursing (negative pregnancy test) * No ongoing hemoptysis * No cerebrovascular accident within the past 12 months * No peripheral vascular disease with claudication while walking less than 1 block * No history of clinically significant bleeding * No deep venous thrombosis or pulmonary embolus within the past year * No significant cardiovascular disease, defined as NYHA class II-IV congestive heart failure, angina pectoris requiring nitrate therapy, or myocardial infarction within the past 6 months * No uncontrolled hypertension, defined as systolic BP \> 160 mm Hg and/or diastolic BP \> 90 mm Hg while on medication * No preexisting thyroid abnormality whose thyroid function cannot be maintained in the normal range by medication * No uncontrolled psychiatric disorder * No delayed healing of wounds, ulcers, and/or bone fractures * No currently active second malignancy except nonmelanoma skin cancer (patients are not considered to have a 'currently active' malignancy if they have completed anticancer therapy and are considered by their physician to be at less than 30% risk of relapse) * No more than one prior systemic therapy for RCC * No prior vascular endothelial growth factor receptor agents * No concurrent systemic corticosteroid therapy (except replacement therapy for adrenal insufficiency) o Topical and/or inhaled steroids allowed * No concurrent full-dose oral or parenteral anticoagulation o Low-dose warfarin (1 mg) for maintenance of catheter patency or daily prophylactic aspirin allowed * No concurrent Hypericum perforatum (St. John's wort) * No concurrent ketoconazole, itraconazole, ritonavir, rifampin, or products containing grapefruit juice * No concurrent hormonal therapy or chemotherapy o Concurrent hormones administered for non-disease related conditions (e.g., insulin for diabetes) allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity of Intrapatient Dose Escalation of Sorafenib Tosylate | Study completion | To evaluate the toxicity of dose escalating sorafenib, an estimation of the percentage of patients who are unable to tolerate those escalated doses will be made. Patients will be dose escalated every 4 weeks until a maximum dose of 800 mg BID is reached. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | from the start of the treatment until disease progression/recurrence | The proportion of subjects with an objective response of complete or partial based on the RECIST Criteria |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sorafenib sorafenib tosylate: initial dose of Sorafenib will be administered orally with a dose of 400 mg twice a day, daily.Intrapatient dose escalation will occur providing no dose limiting toxicity (Grade 3 or 4) is observed. Dose level 2 600mg. Dose level 2 800mg
flow cytometry: 15 ml of blood drawn for flow cytometry of T4/T8, NK, CD25+, and Fox p3 testing obtained at baseline and on days 28, 56, 84, and 112
laboratory biomarker analysis: 15 ml of plasma and urine for storage and future determination of VEGF concentration will be obtained at baseline.10 ml of plasma and urine for storage and future determination of VEGF concentration will be obtained on days 28, 56, 84 and 112 | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | Sorafenib |
|---|---|
| Age, Customized Patients greater than or equal to 19 years of age | 14 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 14 |
| other Total, other adverse events | 11 / 14 |
| serious Total, serious adverse events | 2 / 14 |
Outcome results
Primary
Toxicity of Intrapatient Dose Escalation of Sorafenib Tosylate
To evaluate the toxicity of dose escalating sorafenib, an estimation of the percentage of patients who are unable to tolerate those escalated doses will be made. Patients will be dose escalated every 4 weeks until a maximum dose of 800 mg BID is reached.
Time frame: Study completion
Population: Evaluation of this data is not possible as the investigator performing the analysis has left the study center prior to completing the analysis and data was not provided.
Secondary
Response Rate
The proportion of subjects with an objective response of complete or partial based on the RECIST Criteria
Time frame: from the start of the treatment until disease progression/recurrence
Population: Evaluation of this data is not possible as the investigator performing the analysis has left the study center prior to completing the analysis and data was not provided.