Sorafenib in Treating Patients With Metastatic Kidney Cancer That Has Not Responded to Sunitinib or Bevacizumab

A Phase II Study of Sorafenib in Patients With Metastatic Renal Cell Carcinoma (RCC) Refractory to SU11248 or Bevacizumab Therapy

RATIONALE: Sorafenib 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.

PURPOSE: This phase II trial is studying how well sorafenib works in treating patients with metastatic kidney cancer that has not responded to sunitinib or bevacizumab.

Study Overview

• Status: Completed
• Conditions: Kidney Cancer
• Intervention / Treatment: Drug: sorafenib tosylate

Detailed Description

OBJECTIVES:

Primary

• To determine the tumor burden reduction rate in patients with sunitinib malate- or bevacizumab-refractory, metastatic clear cell renal cell carcinoma treated with sorafenib tosylate.

Secondary

• To determine the safety of sorafenib tosylate in these patients.
• To record the duration of tumor reduction, time to disease progression, and overall survival of patients treated with sorafenib tosylate.

OUTLINE: Patients receive oral sorafenib tosylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Sammons 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

DISEASE CHARACTERISTICS:

• Histologically confirmed renal cell carcinoma with a component of clear cell histology

  • Metastatic disease

• Disease progression, as defined by RECIST criteria, after prior treatment with sunitinib malate or bevacizumab

  • Patients must have received ≥ 1 course (4 weeks) of sunitinib malate or ≥ 2 doses of bevacizumab AND have RECIST-defined objective progression during or within 4 months after completing treatment with sunitinib malate or bevacizumab
• Measurable disease by RECIST criteria
• CNS metastases allowed provided patient has undergone prior surgery and/or radiotherapy AND has no evidence of further CNS disease progression by CT scan or MRI ≥ 2 weeks after treatment of CNS metastases

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%
• WBC ≥ 3,000/μL
• Absolute neutrophil count ≥ 1,500/μL
• Platelet count ≥ 75,000/μL
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST/ALT ≤ 2.5 times ULN
• Creatinine ≤ 2.0 times ULN
• Negative pregnancy test

• No significant cardiovascular disease, including any of the following:

  • Congestive heart failure (New York Heart Association class III-IV heart disease)
  • Active angina pectoris requiring nitrate therapy
  • Uncontrolled dysrhythmias
  • Cardiovascular event within the past 6 months (e.g., transient ischemic attack/cerebrovascular accident, myocardial infarction, or vascular surgery)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 2 weeks since prior systemic therapy, radiotherapy, or major surgery and recovered
• No prior sorafenib tosylate
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• No concurrent prophylactic growth factors

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: Sorafenib; Chemotherapy single agent systemic. Sorafenib given up to 600mg orally every 12 hours for up to 10 months (40 weeks).	Drug: sorafenib tosylate; Sorafenib (BAY 43-9006) is an oral multi-kinase inhibitor targeting both tumor cells and the tumor vasculature. Patients with metastatic RCC meeting eligibility criteria will receive 400 mg BID of sorafenib in a single-arm phase II study. Treatment will be administered on an outpatient basis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Burden Reduction Rate (TBRR)	The primary endpoint of the study is defined as the percentage of patients who experience larger than or equal to 5% reduction in tumor burden as measured by RECIST-defined target lesions without progression of non-target lesions or the appearance of any new lesions, confirmed at least 4 weeks after first documentation. RECIST criteria will be used for the purpose of designating target lesions, calculating total tumor burden (the sum of the unidimensional measurement of target lesions) and defining disease progression.Additional RECIST-defined partial or complete responses will be recorded.	at 8 weeks (2cycles of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival measured in months and summarized using the Kaplan-Meier method. This will be calculated from the date of registration on-study to the dates of documented evidence of progression and death, respectively.	followed until progression or death for approximately 3 years
Time to Progression	Time to objective progression will be measured from the start of treatment until the criteria for RECIST-defined progression are met, taking as reference the smallest measurements recorded since the treatment started, including baseline. Progression-free survival measured in months and summarized using the Kaplan-Meier method.	followed to progression for approximately 3 years
Duration of Overall Response (Tumor Burden Reduction)	Measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented.	followed for overall response for approximately 3 years

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Brian I. Rini, MD, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: March 19, 2009
• First Submitted That Met QC Criteria: March 19, 2009
• First Posted (Estimate): March 20, 2009

Study Record Updates

• Last Update Posted (Estimate): July 23, 2014
• Last Update Submitted That Met QC Criteria: July 14, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: stage IV renal cell cancer; recurrent renal cell cancer; clear cell renal cell carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: CASE11805 (Other Identifier: Case Comprehensive Cancer Center); P30CA043703 (U.S. NIH Grant/Contract); 05-167 (Other Identifier: Cleveland Clinic IRB)