A Study of Neoadjuvant Sutent for Patients With Renal Cell Carcinoma

Study Overview
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Brief Summary
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Study Hypothesis: Patients with local renal cell carcinoma who are treated neoadjuvantly with Sutent may show a radiologic response to the study drug (Sutent). The study is looking at the neoadjuvant (pre-surgery) administration of Sutent in patients with localized kidney cancer. The purpose of this research is also to evaluate both the safety and effectiveness of Sutent in this patient population.

Detailed Description
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Sutent will be given at 50 mg once daily for 4 consecutive weeks followed by a 1 week rest period. The dosage may change during the cycle due to possible drug toxicities. The nephrectomy will then take place following a one-week washout period. After surgery, patients will have follow-up visits at 6 weeks and 3 months. Patients will be followed for 3 years after completions to assess late toxicities, time to progression and progression-free survival.

Official Title
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A Phase II, Single Arm, Prospective Study of Neoadjuvant Sutent for Patients With Renal Cell Carcinoma

Conditions
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Renal Cell Carcinoma

Intervention / Treatment
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* Drug: Sunitinib Malate (Sutent)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed renal cell carcinoma with a component of clear (conventional) cell histology, which has been assessed with biopsy at screening. Locally confined tumour ≤ 7 cm Has not undergone nephrectomy and is a candidate for surgical treatment of renal cell carcinoma Male or female, 18 years of age or older ECOG performance status 0 or 1 Adequate organ function as defined by the following criteria: Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) less than or equal to 2.5 x central laboratory upper limit of normal (CL-ULN), or AST and ALT less than or equal to 5 x CL ULN if liver function abnormalities are due to underlying malignancy Total serum bilirubin less than or equal to 1.5 x CL-ULN Absolute neutrophil count (ANC) greater than or equal to 1500/mL Platelets greater than or equal to 100,000/mL Hemoglobin greater than or equal to 9.0 g/dL Serum calcium less than or equal to 12.0 mg/dL Serum creatinine less than or equal to 1.5 x CL-ULN Prothrombin time (PT) less than or equal to 1.5 x CL-ULN Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures Exclusion Criteria: Prior therapy of any kind for RCC (including nephrectomy, immunotherapy, chemotherapy, radiation, hormonal, or investigational therapy) Abnormal ECG- including long QT/QTc interval, AV block or arrythmia Tumour associated with local extension into adjacent tissues Tumour associated with renal/vena caval thrombus Tumour associated with lymphadenopathy (lymph node > 1 cm) Evidence of rapidly progressive disease or other factors requiring surgery to take place before the 12 weeks scheduled for neoadjuvant treatment Major surgery within 4 weeks of commencing study treatment Any toxicity with a NCI CTCAE grade 3 or 4 Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell carcinoma, squamous cell skin cancer, or in situ cervical cancer Evidence of metastatic renal cell carcinoma Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness Current treatment on another clinical trial Pregnancy or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sunitinib Malate (Sutent)<br>Sutent will be given at 50 mg once daily for 4 consecutive weeks followed by a 2 week rest period to comprise a complete cycle of 6 weeks. Patients will then continue on Sutent for another cycle of 4 consecutive weeks | Drug: Sunitinib Malate (Sutent)<br>* Sutent will be given at 50 mg once daily for 4 consecutive weeks followed by a 1 week washout period. The dosage may change during the cycle due to possible drug toxicities. The nephrectomy will then take place following a one-week washout period.<br>* Other names: Sutent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the radiologic response rate associated with 1 cycle of Sutent for neoadjuvant treatment of patients with renal cell carcinoma |  | 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the change in tumour vascularity in response to 1 cycle of neoadjuvant treatment of patients with renal cell carcinoma |  | 5 weeks | 
| To assess the change in expression of the following tissue markers; PDGF-alpha, PDGF-Beta, Flt-3, VEGFR and c-KIT, as compared to pre-treatment biopsy tissue as well as to stage, gender and age-matched controls |  | 5 weeks | 
| To evaluate the safety and tolerability of Sutent given preoperatively |  | 5 weeks | 
| To assess late toxicities, time to progression, progression free survival, and survival |  | 5 weeks - 3 years | 
| A DNA microarray will be used for gene expression profiling of the tissue harvested at biopsy and surgery to investigate differential expression profiles and their association with Sutent sensitivity or resistance |  | 5 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Localized, Renal Cell Carcinoma, Neoadjuvant, Sunitinib Malate (Sutent)