Clinical trial NCT00747305: Sunitinib Before and After Surgery in Treating Patients With Metastatic Kidney Cancer That Can Be Removed By Surgery
Official title: Biomarkers of Tumor Angiogenesis and Response to Sunitinib Maleate in Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Kidney Cancer
Keywords: stage IV renal cell cancer
clear cell renal cell carcinoma
recurrent renal cell cancer
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
First posted: 2008-09-05
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Describe the gene expression of VEGF and non-VEGF from eligible patients being treatment with Sunitinib.
timeFrame: at various points throughout the study duration
measure: Describe the association between quantitative gene expression levels of VEGF and non-VEGF angiogenic factors with the clinical efficacy of Sunitinib as measured by response, duration or response and time to progression
timeFrame: at various points throughout the study duration
Secondary outcomes:
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: Harry A. Drabkin, MD
role: PRINCIPAL_INVESTIGATOR
References: