Sunitinib Before and After Surgery in Treating Patients With Metastatic Kidney Cancer That Can Be Removed By Surgery

Harry Drabkin

Status and phase: Terminated; Phase 1

Conditions: Kidney Cancer

Treatments: Genetic: gene expression analysis; Genetic: reverse transcriptase-polymerase chain reaction; Procedure: neoadjuvant therapy; Other: immunohistochemistry staining method; Procedure: therapeutic conventional surgery; Procedure: adjuvant therapy; Other: laboratory biomarker analysis; Genetic: western blotting; Drug: sunitinib malate

Study type: Interventional

Funder types: Other

Identifiers

NCT00747305

CDR0000612590

MUSC-101219

Details and patient eligibility

About

RATIONALE: Sunitinib 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 sunitinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This clinical trial is studying how well sunitinib works when given before and after surgery in treating patients with metastatic kidney cancer that can be removed by surgery.

Full description

OBJECTIVES:

• To describe the gene expression of VEGF and non-VEGF angiogenic growth factor genes in kidney cancer specimens from patients with metastatic renal cell carcinoma treated with sunitinib malate.
• To describe the association between quantitative gene expression levels of VEGF and non-VEGF angiogenic factors and clinical efficacy of this drug, as measured by response, duration of response, and time to progression in these patients.

OUTLINE: Patients receive oral sunitinib malate once daily for 8 weeks. Within 2 weeks after completion of neoadjuvant chemotherapy, patients undergo a nephrectomy and evaluation for response to therapy. Beginning 4-8 weeks after surgery patients resume oral sunitinib malate once daily for up to 12 months in the absence of disease progression or unacceptable toxicity.

Patients with disease progression after 8 weeks of adjuvant treatment receive treatment off study with other agents.

Viable (non-necrotic) tumor and non-tumor kidney tissue samples are obtained at the time of nephrectomy for correlative biomarker studies. Tissue samples are analyzed for gene expression of VEGF and non-VEGF angiogenic factors by real-time RT-PCR, western blot, and/or IHC. Blood samples are obtained at baseline and at 4 and 8 weeks for evaluation of circulating levels of VEGF and selected chemokines.

After completion of study therapy, patients are followed monthly.

Enrollment: 17 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Diagnosis of clear cell renal cell carcinoma

  • Metastatic disease
  • Primary tumor is considered amenable to surgery

• Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as > 20 mm by conventional techniques or as > 10 mm by spiral CT scan

• No untreated brain metastases

  • Treated brain metastases allowed provided lesion has been stable on two consecutive CT or MRI scans separated by ≥ 2 months

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Leukocytes ≥ 3,000/μL

• ANC ≥ 1,500/μL

• Platelet count ≥ 75,000/μL

• Hemoglobin ≥ 8.5 g/dL

• Total Bilirubin ≤ 2 times upper limits of normal (ULN)

• AST and ALT ≤ 2.5 times ULN

• Creatinine ≤ 2.5 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Able to undergo nephrectomy and treatment with sunitinib malate

• No history of allergic reactions attributed to compounds of similar chemical or biological composition to sunitinib malate

• No uncontrolled intercurrent illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness/social situations that would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

• No prior systemic treatment with sunitinib malate
• No other concurrent investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients
• Concurrent medications or substances known to affect, or with the potential to affect, the activity or pharmacokinetics of sunitinib malate allowed at the discretion of the principal investigator

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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17 participants in 1 patient group

Sunitinib

Experimental group

Description:

Sunitinib will be administered for 8 weeks prior to sugery

Treatment:

Procedure: therapeutic conventional surgery

Procedure: neoadjuvant therapy

Other: immunohistochemistry staining method

Other: laboratory biomarker analysis

Procedure: adjuvant therapy

Drug: sunitinib malate

Genetic: western blotting

Genetic: reverse transcriptase-polymerase chain reaction

Genetic: gene expression analysis