Sunitinib Malate in Treating Patients With Previously Untreated Metastatic Kidney Cancer

A Phase II Study of Intermittent Sunitinib in Previously Untreated Patients With Metastatic Renal Cell Carcinoma

RATIONALE: Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well sunitinib malate it works in treating patients with previously untreated metastatic kidney cancer.

Study Overview

• Status: Completed
• Conditions: Clear Cell Renal Cell Carcinoma; Stage IV Renal Cell Cancer
• Intervention / Treatment: Drug: sunitinib malate

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the feasibility of intermittent sunitinib therapy in patients with metastatic renal cell carcinoma (RCC).

SECONDARY OBJECTIVES:

I. To determine the clinical outcome (response rate and overall progression-free survival) in metastatic renal cell carcinoma patients treated with intermittent sunitinib therapy.

II. To evaluate the toxicity of intermittent sunitinib therapy in patients with metastatic renal cell carcinoma.

III. To assess the feasibility of detecting circulating tumor cells (CTCs) in RCC patients and investigate the association between the VEGF -634 genotype and the occurrence of hypertension in sunitinib-treated RCC patients.

OUTLINE:

Patients receive oral sunitinib malate once daily on days 1-28. Sunitinib dosing schedule may be changed to 14 days on followed by 7 days off, and repeated for a 6-week cycle, at the discretion of the treating physician for toxicity purposes. Cycles will be defined as 6 week intervals regardless of dosing interruptions. All patients will be treated for 4 cycles in the absence of unacceptable toxicity or RECIST-defined progressive disease.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

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:

• Histologically or cytologically-proven advanced RCC with a component of clear cell histology
• Measurable disease per RECIST criteria
• ECOG performance status 0-1
• Prior nephrectomy is NOT required
• Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 x laboratory upper limit of normal (ULN)
• Total serum bilirubin ≤ 2.0 x ULN
• Absolute neutrophil count (ANC) ≥ 1500/uL
• Platelets ≥ 100,000/uL
• Hemoglobin ≥ 8.0 g/dL (transfusion permitted)
• Serum calcium ≤ 12.0 mg/dL
• Serum creatinine ≤ 2.5 mg/dL
• Patients with history of brain metastases can be enrolled at a minimum of 2 weeks following the completion of surgery, gamma knife or whole brain radiotherapy; repeat brain MRI not required for eligibility
• 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

Exclusion Criteria:

• Prior systemic treatment for advanced RCC. Prior adjuvant therapy (any drug) is allowed if end of adjuvant therapy was more than 1 year prior to start of sunitinib on this protocol.
• Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, severe peripheral vascular disease (claudication) or procedure on peripheral vasculature, coronary/peripheral artery bypass graft, New York Heart Association grade II or greater congestive heart failure, cerebrovascular accident or transient ischemic attack, clinically significant bleeding or pulmonary embolism
• Hypertension that cannot be controlled by medications to < 160/90 mmHg
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness
• Pregnancy or breastfeeding
• Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 42 days for at least 4 courses in the absence of disease progression or unacceptable toxicity.	Drug: sunitinib malate; Given orally; Other Names: Sutent; SU011248; SU11248; sunitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility as Assessed by Proportion of Patients Eligible for Intermittent Therapy Who Actually Receive it	Treatment repeats every 42 days for at least 4 courses in the absence of disease progression or unacceptable toxicity.	after 6 months of treatment (4 cycles)

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Circulating Tumor Cells	Pre-treatment, day 1, and day 28 of every cycle
Relationship Between Hypertension and Germline VEGF Single Nucleotide Polymorphism (SNP) -634 Genotype	Day 28 of each cycle

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Investigators: Principal Investigator: Brian Rini, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2010
• Primary Completion (Actual): June 20, 2013
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: July 6, 2010
• First Submitted That Met QC Criteria: July 6, 2010
• First Posted (Estimate): July 8, 2010

Study Record Updates

• Last Update Posted (Actual): September 14, 2018
• Last Update Submitted That Met QC Criteria: August 17, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• 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: CASE8809; NCI-2010-01391 (Other Identifier: NCI/CTRP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No