Sorafenib in Treating Patients With Locally Advanced or Metastatic Kidney Cancer

Not Applicable

Terminated

Conditions: Hereditary Clear Cell Renal Cell Carcinoma
Kidney Cancer

Interventions: Drug: Sorafenib

Registration Number: NCT00727532

Lead Sponsor: Northwestern University

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. Giving sorafenib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This clinical trial is studying how well sorafenib works in treating patients with locally advanced or metastatic kidney cancer.

Detailed Description: OBJECTIVES:

Primary

* To demonstrate the feasibility and safety of sorafenib tosylate when given prior to nephrectomy or metastasectomy.

* To evaluate the ability of diffusion-weighted magnetic resonance imaging (DW-MRI) to detect early and ongoing microstructural changes in primary and metastatic renal cell carcinoma lesions during neoadjuvant therapy with sorafenib tosylate.

* To correlate early and ongoing microstructural changes in primary and metastatic renal cell carcinoma lesions with pathologic and clinical findings at the time of nephrectomy or metastasectomy.

* To evaluate the ability of changes in DW-MRI to predict subsequent favorable response to treatment (complete or partial response or stable disease) after 4 weeks of therapy.

OUTLINE: Patients receive oral sorafenib tosylate twice daily on days 1-28. Patients then undergo a nephrectomy or metastasectomy in week 5. Patients with residual metastatic disease may continue sorafenib tosylate twice daily and undergo a diffusion-weighted MRI (DW-MRI) every 8 weeks in the absence of disease progression or unacceptable toxicity.

Patients undergo a DW-MRI of the abdomen and pelvis at baseline and prior to week 5 to evaluate microstructure tumor changes and to allow for prediction of sorafenib tosylate benefit. DW-MRI results are correlated with surgical and pathologic findings obtained at week 5.

Resected tumor tissue are analyzed for vascular density and to distinguish apoptotic cell death from necrotic cell death via immunohistochemistry and to measure apoptotic cell death via TUNEL assay.

After completion of study treatment, patients are followed every 3 months for 2 years.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 9

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sorafenib	Sorafenib	Eligible patients undergo pre-treatment DW-MRI of the abdomen and pelvis. Patient then receive Sorafenib 400mg orally twice daily on days 1-28. Following completion of 28 days of sorafenib, patients obtain a second DW-MRI.

Primary Outcome Measures

Name	Time	Method
Percentage Change in Difference in Apparent Diffusion Coefficient Between Baseline and Week 5	Baseline and week 5	Mean Difference in Apparent Diffusion Coefficient \[Time Frame: Baseline and Week 5\] To assess whether changes in the apparent diffusion coefficient (ADC) during neoadjuvant sorafenib treatment are detectable in locally advanced or metastatic kidney cancer. The ADC value will be calculated at baseline (within 28 days of initiating sorafenib) and Week 5, and the mean difference will be calculated. The percent change between this mean difference is reported. Week 5 ADC value minus baseline ADC value/divided by baseline ADC value was calculated for each participant. Apparent diffusion coefficient (ADC), obtained by measuring diffusion values at magnetic resonance imaging (MRI), is a measure of water mobility. Lower values correspond to tumor and higher values are consistent with cysts. With sorafenib therapy, the amount of free water may increase in a lesion due to necrosis, and as a result the ADC may increase in value.
Change in Tumor Size From Baseline to Approximately 29-34 Days After Completion of Neoadjuvant Sorafenib Treatment	Just prior to study week 5	Tumors were measured at baseline and approximately 29-34 days after completion of neoadjuvant treatment with sorafenib (just prior to surgery). Tumors were assessed by RECIST response criteria.

Secondary Outcome Measures