Magnetic Resonance Imaging (MRI) in Predicting Response to Sunitinib Malate in Patients With Locally Advanced or Metastatic Kidney Cancer

An Imaging and Histopathologic Study to Predict Response to Sunitinib Therapy in Patients With Metastatic or Locally Advanced Renal Cell Carcinoma

Rationale: Diagnostic procedures, such as MRI, may help doctors predict a patient's response to treatment and help plan the best treatment.

Purpose: This clinical trial is studying MRI in predicting response to sunitinib malate in patients with locally advanced or metastatic kidney cancer.

Study Overview

• Status: Completed
• Conditions: Renal Cell Carcinoma; Stage III Renal Cell Cancer; Stage IV Renal Cell Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Procedure: dynamic contrast-enhanced magnetic resonance imaging; Drug: sunitinib malate; Other: immunohistochemistry staining method; Genetic: mutation analysis

Detailed Description

Primary Objectives:

I. To correlate tumor vascular permeability by DCE-MRI with clinical outcome for patients treated with sunitinib (PFS).

II. To correlate genetic and histologic characteristics of the primary tumor with vascular permeability by DCE-MRI.

Secondary Objectives:

I. To correlate genetic and histologic characteristics of the primary tumor with clinical outcome for patients treated with sunitinib.

II. Samples will be collected for potential future exploratory analyses of pharmacokinetic and pharmacogenomic parameters.

Outline: Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 42 days in the absence of disease progression or unacceptable toxicity.

Patients undergo dynamic contrast-enhanced MRI at baseline and after the first 4 weeks of sunitinib malate.

• Study Type: Observational
• Enrollment (Actual): 43

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of the University of Pennsylvania

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

• AJCC stage IV or locally advanced (or inoperable) renal cell carcinoma for which archival tissue is available
• No prior anti-angiogenic therapy
• Prior radiation therapy to a symptomatic site of disease is allowed
• ECOG performance status of 0, 1 or 2
• White Blood Count >= 3,000/mm^3
• Absolute Granulocyte Count >= 1,500/mm^3
• Platelet Count >= 100,000/mm^3
• Serum creatinine =< 2.0 x upper limit of normal (ULN) OR serum creatinine clearance (CrCl) >= 40 ml/min
• Total Bilirubin =< 1.5 x ULN (< 3.0 x ULN in the presence of Gilbert's disease)
• AST/ALT =< 2.5 x ULN (=< 5.0 ULN in the presence of liver metastases)
• INR =< 1.5 and a PTT within normal limits; patients who are taking warfarin must have documentation of an INR =< 1.5 and a PTT within normal limits prior to the initiation of anticoagulation to rule out a baseline coagulopathy
• Patient must not have pre-existing thyroid abnormality with thyroid stimulating hormone that cannot be maintained in the normal range with medication
• Patient must not have hypertension that cannot be controlled by medications (diastolic blood pressure >= 100 mm Hg despite optimal medical therapy)
• Patient must not have ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade >= 2
• Patients must not receive any other investigational agents during the period on study
• Patients must not have a history or clinical evidence of brain metastasis; however, patients with resected or radiated brain metastases are eligible
• Patients must not have a serious intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, clinically significant cardiovascular disease (e.g., uncontrolled hypertension, myocardial infarction, unstable angina), New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication
• Patients must not have a serious intercurrent illness including, but not limited to, grade II or greater peripheral vascular disease within 1 year prior to study entry, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients must not be taking cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or phenobarbital), rifampin or St. John's wort
• Women must not be pregnant or breast-feeding
• All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal, barrier method of birth control, or abstinence) prior to study entry and for the duration of study participation

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Arm I; Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 42 days in the absence of disease progression or unacceptable toxicity. Patients undergo dynamic contrast-enhanced MRI at baseline and after the first 4 weeks of sunitinib malate.

Other: laboratory biomarker analysis; Correlative study; Other: pharmacological study; Correlative study; Other Names: pharmacological studies; Procedure: dynamic contrast-enhanced magnetic resonance imaging; Undergo DCE-MRI; Other Names: DCE-MRI; Drug: sunitinib malate; Given orally; Other Names: Sutent; SU011248; SU11248; sunitinib; Other: immunohistochemistry staining method; Correlative study; Other Names: immunohistochemistry; Genetic: mutation analysis; Correlative study

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Progression-free survival
Correlation of tumor vascular permeability as measured by dynamic contrast-enhanced MRI with clinical outcome and with tumor angiogenesis as measured by immunohistochemistry (IHC)

Secondary Outcome Measures

Outcome Measure
Tumor regression as measured by Response Evaluation Criteria In Solid Tumors (RECIST) criteria

Collaborators and Investigators

• Sponsor: Abramson Cancer Center of the University of Pennsylvania
• Investigators: Principal Investigator: Stephen Keefe, Abramson Cancer Center of the University of Pennsylvania

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): November 1, 2018

Study Registration Dates

• First Submitted: December 2, 2009
• First Submitted That Met QC Criteria: December 2, 2009
• First Posted (Estimate): December 4, 2009

Study Record Updates

• Last Update Posted (Actual): June 25, 2019
• Last Update Submitted That Met QC Criteria: June 21, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: recurrent renal cell cancer
• 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: UPCC 03809; NCI-2009-01414

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No