Sorafenib in Treating Patients With Locally Advanced or Metastatic Kidney Cancer

NCT ID: NCT00727532

Last Updated: 2019-05-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2013-09-30

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.

Conditions

Hereditary Clear Cell Renal Cell Carcinoma; Kidney Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Sorafenib

Intervention Type: DRUG

400mg by mouth twice daily for 28 consecutive days

Interventions

Sorafenib

400mg by mouth twice daily for 28 consecutive days

Intervention Type: DRUG

Other Intervention Names

Nexavar

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed newly diagnosed clear cell renal cell carcinoma, meeting 1 of the following criteria:

• Localized disease, as evidenced by intact, bulky, and primary renal lesions (T1 > 3 cm, any T2, T3, or T4) appropriate for nephrectomy
• Limited metastatic disease, as evidenced by any renal primary (T1 > 3 cm, any T2, T3, or T4) appropriate for cytoreductive nephrectomy
• Isolated abdominal/pelvic recurrence with limited metastatic burden (minimum size > 2 cm) appropriate for metastasectomy
• No known brain metastasis

• Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group performance status 0-1
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• Alanine aminotransferase and Aspartate aminotransferase ≤ 2.5 times ULN (≤ 5 times ULN with liver involvement)
• Creatinine ≤ 1.5 times ULN
• Estimated glomerular filtration rate > 30 mL/min (for patients receiving Gd-enhanced MRI)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception prior to, during (men and women), and for at least 3 months after (men) completion of study therapy
• Adequate cardiac and pulmonary status for operative therapy
• No active clinically serious infection > CTCAE grade 2
• No known HIV, hepatitis B, or hepatitis C infections
• No serious non-healing wound, ulcer, or bone fracture
• No significant traumatic injury within the past 4 weeks
• No pulmonary hemorrhage/bleeding event ≥ CTCAE grade 2 within the past 4 weeks
• No other hemorrhage/bleeding event ≥ CTCAE grade 3 within the past 4 weeks
• No history of an uncontrolled bleeding disorder including, but not limited to, any of the following:

• Bleeding diathesis
• Coagulopathy
• No cardiac disease or condition including, but not limited to, any of the following:

• New York Heart Association class II-IV congestive heart failure
• Unstable angina (anginal symptoms at rest)
• New onset angina beginning within the last 3 months
• Myocardial infarction within the past 6 months
• Cardiac ventricular arrhythmias requiring antiarrhythmic therapy
• No uncontrolled hypertension (i.e., systolic blood pressure [BP] > 150 mm Hg or diastolic BP > 100 mm Hg) despite optimal medical management
• No thrombolic or embolic events within the past 6 months (e.g., cerebrovascular accident including transient ischemic attacks)
• No condition that impairs the ability to swallow whole pills
• No malabsorption problem
• No contraindication to MRI, including, but not limited to, any of the following:

• Ferromagnetic implants
• Dental work
• Pacemakers
• Metallic implants
• Severe claustrophobia which precludes closed MRI testing
• No known or suspected allergy to sorafenib tosylate
• No contraindication or allergy to gadolinium (e.g., end stage renal disease requiring hemodialysis)
• No intercurrent illness or situation which, in the judgment of the investigator, would affect assessments of clinical status and study endpoints significantly

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 4 weeks since prior major surgery or open biopsy
• No prior therapy with tyrosine kinase or vascular endothelial growth factor inhibitors (e.g., sunitinib malate, sorafenib, or bevacizumab)
• No concurrent Hypericum perforatum (St. John's wort) or rifampin
• No concurrent use of illicit drugs or other substances that may, in the opinion of the investigator, have a reasonable chance of contributing to toxicity or interfering with study results

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Timothy M. Kuzel, MD

Role: PRINCIPAL_INVESTIGATOR

Robert H. Lurie Cancer Center

Locations

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

Countries

United States

Other Identifiers

P30CA060553

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NU-IRB-STU00003123

Identifier Type: OTHER

Identifier Source: secondary_id

NU 07U1

Identifier Type: -

Identifier Source: org_study_id