Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Recurrence

Carcinoma

Body Weight

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

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.

400mg by mouth twice daily for 28 consecutive days

Timothy M. Kuzel, MD

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.

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.

Sorafenib in Treating Patients With Locally Advanced or Metastatic Kidney Cancer

Correlation of Pathologic Findings After Neo-adjuvant Sorafenib With Results of Diffusion-Weighted Magnetic Resonance Imaging in Patients With Locally Advanced or Metastatic Clear Cell Renal Cell Carcinoma

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.

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.

National Cancer Institute (NCI)

Northwestern University

Sorafenib 400mg orally twice daily on days 1-28

sorafenib tosylate: 400mg by mouth twice daily for 28 consecutive days

diffusion-weighted magnetic resonance imaging: At baseline and just prior to surgery after sorafenib treatment

Sorafenib 400mg orally twice daily on days 1-28

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

T1>3cm

Participants must have bulky (T1\>3cm,any T2, T3,orT4) renal cell carcinoma undergoing nephrectomy.Staging defined as:T1\>3cm: Tumor ≤7cm in greatest dimension but \>3cm, limited to the kidney;T2:Tumor \>7cm, limited to the kidney;T3:Tumor extends into major veins but not into the ipsilateral adrenal gland \& not beyond Gerota fascia (the fibrous layer that surrounds the kidney \& nearby fatty tissue);T4:Tumor invades beyond Gerota fascia(including contiguous extension into ipsilateral adrenal gland).The higher the number after the T, the larger the tumor or more it has grown into nearby tissues.

Renal cell carcinoma Clinical Staging

The trial did not reach the original goal of 10 subjects. Only 9 out of 10 patients had been enrolled, with no accrual for a period of more than 1 year. Therefore it was administratively closed by the Data Monitoring Committee.

Results Entry Administrator

Percentage Change in Difference in Apparent Diffusion Coefficient Between Baseline and Week 5

Change in Tumor Size From Baseline to Approximately 29-34 Days After Completion of Neoadjuvant Sorafenib Treatment

Changes in MRI will be correlated with findings of necrosis. Amount of necrosis will be measured at baseline and at time of surgery. Percentage change for necrosis will be calculated from baseline and time of surgery.

Percentage Change of Necrosis From Baseline to Surgery

Overall Study

Spots Global Cancer Trial Database for hereditary clear cell renal cell carcinoma