Study of Sunitinib in Subjects With High Risk Renal Cell Carcinoma

Phase II, Open Label, Single Center Study of Sunitinib in Subjects With High Risk Renal Cell Carcinoma

This study is designed to explore the molecular modulatory effect of Sunitinib when given in a neoadjuvant setting prior to radical or partial nephrectomy. The study will evaluate aforementioned outcomes in 30 patients at a dose of 50mg/day for 4 weeks followed by surgery 2-4 weeks following the last dose.

Study Overview

• Status: Withdrawn
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Drug: Sunitinib; Other: Tumor biopsy; Procedure: Nephrectomy; Other: Biomarkers

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must be at least 18 years of age
• Must be eligible to undergo a radical or partial nephrectomy
• Clinical stage T1b, T2, T3, T4 and/or N1 disease as documented by abdomen/pelvis CT scan, or MRI and chest x-ray or CT chest
• Patients must have a performance status on the ECOG scale of 0-1
• Patients must have a pretreatment wbc > 3.0, granulocyte count > 1000/mm3, hemoglobin > 8.5 g/dL, platelet count > 100,000/mm3 and a normal PT and PTT
• Patients must have a serum creatinine < 2.0 mg/dL
• Patients must have adequate hepatic function with a serum bilirubin < upper limit of normal and AST/ALT < 2.5 x upper limit of normal

Exclusion Criteria:

• Radiographic evidence of metastatic disease
• Prior administration of immunotherapy/biotherapy/hormonal or radiation for renal cell carcinoma
• Active secondary malignancies (other than basal cell carcinoma of the skin)
• Serious, nonhealing wound, ulcer, or bone fracture
• Clinically significant cardiovascular disease, New York Heart Association Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication or Grade II or greater peripheral vascular disease within 1 year preceding Day 0
• Any history or radiologic evidence of central nervous system disease
• Active infection requiring parenteral antibiotics at the time of the first Sunitinib administration
• Current or recent (within the 10 days preceding Day 0) use of oral or parenteral anticoagulants (except as required to maintain patency of preexisting, permanency indwelling IV catheters), or aspirin
• Current, recent (within the 4 weeks preceding Day 0), or planned participation in another experimental drug study

• Screening clinical laboratory values:

  • ANC of < 1000/uL
  • Platelet count of < 100,000/uL
  • Total bilirubin > 2.0 mg/dL
  • AST or ALT > 2.5 times the upper limit of normal
  • Serum creatinine of > 2.0 mg/dL
  • Hemoglobin of < 9 gm/dL (may be transfused to maintain or exceed this level)
  • Ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade > 2
  • Prolonged QTc interval on baseline EKG
  • Uncontrolled hypertension (>150/100 mm Hg despite optimal medical therapy)
  • Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
  • Patients receiving CYP3A4 inducers or inhibitors; patients should not take grapefruit juice or St. John's Wort while on the study
  • History of psychiatric disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications
  • Unable to take medication by mouth

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Treatment; See intervention descriptions

Drug: Sunitinib; 50mg/day for 4 weeks; Other Names: Sutent; Other: Tumor biopsy; Conducted prior to administration of sunitinib therapy; Procedure: Nephrectomy; Nephrectomy 2-4 weeks after last dose of Sunitinib; Other: Biomarkers; Biomarker evaluation of blood prior to treatment, after 4 weeks of Sunitinib administration, and every three months for a year after surgery. Biomarker evaluation of tissue prior to 4 week administration of Sunitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to clinical recurrence after surgery for high risk localized disease.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity of Sunitinib when administered as neoadjuvant therapy prior to surgery	Toxicities will be graded using the NCI Common Toxicity Criteria, version 3.0	1 year
Effect of Sunitinib on pretreatment serum levels of Vascular Endothelial Growth Factor (VEGF). Tissue levels (biopsy and pathological specimen) of total VEGF, HIF-alpha, microvessel density, and apoptotic indices (TUNNEL Staining)		1 year
Radiographically quantifiable evaluation of changes in cellular disorganization (marker of necrosis) and perfusion parameters before and during the administration of Sunitinib.		1 year

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: Pfizer
• Investigators: Principal Investigator: Fairooz Kabbinavar, M.D., University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start: October 1, 2010

Study Registration Dates

• First Submitted: February 16, 2010
• First Submitted That Met QC Criteria: February 16, 2010
• First Posted (ESTIMATE): February 17, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): July 31, 2012
• Last Update Submitted That Met QC Criteria: July 27, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: T2; Kidney Cancer; nephrectomy; T3; T4; T1b; N1
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: 09-07-068