Sorafenib in Treating Patients at Risk of Relapse After Undergoing Surgery to Remove Kidney Cancer

• ClinicalTrials.gov Identifier: NCT00492258
• Recruitment Status: Completed
• First Posted: June 27, 2007
• Last Update Posted: August 12, 2013
• Sponsor: Medical Research Council
• Information provided by: National Cancer Institute (NCI)

Tracking Information

• First Submitted Date: June 25, 2007
• First Posted Date: June 27, 2007
• Last Update Posted Date: August 12, 2013
• Study Start Date: June 2007
• Actual Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 25, 2007): Disease-free survival
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 25, 2007)

• Metastasis-free survival
• Disease-specific survival time
• Overall survival
• Cost effectiveness
• Toxicity

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Sorafenib in Treating Patients at Risk of Relapse After Undergoing Surgery to Remove Kidney Cancer
• Official Title: SORCE: A Phase III Randomised Double-Blind Study Comparing Sorafenib With Placebo in Patients With Resected Primary Renal Cell Carcinoma at High or Intermediate Risk of Relapse

Brief Summary

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. Giving sorafenib after surgery may kill any tumor cells that remain after surgery. It is not yet known whether sorafenib is more effective than a placebo in treating kidney cancer.

PURPOSE: This randomized phase III trial is studying sorafenib to see how well it works compared with a placebo in treating patients at risk of relapse after undergoing surgery to remove kidney cancer.

Detailed Description

OBJECTIVES:

• Compare disease-free survival of patients with resected primary renal cell carcinoma at high- or intermediate-risk of relapse treated with a placebo for 3 years vs a placebo for 2 years and sorafenib tosylate for 1 year vs sorafenib tosylate for 3 years.

OUTLINE: This is a randomized, placebo-controlled, double-blind, open-label, multicenter study. Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive oral placebo twice daily for 3 years in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive oral sorafenib tosylate twice daily for 1 year and oral placebo twice daily for 2 years in the absence of disease progression or unacceptable toxicity.
• Arm III: Patients receive oral sorafenib tosylate twice daily for 3 years in the absence of disease progression or unacceptable toxicity.

Patients in arms I and II with progressive disease may cross over and receive treatment in arm III.

After completion of study treatment, patients are followed periodically.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Kidney Cancer

Intervention

• Drug: sorafenib tosylate
• Procedure: adjuvant therapy

• Study Arms: Not Provided

Publications *

• Blinman PL, Davis ID, Martin A, Troon S, Sengupta S, Hovey E, Coskinas X, Kaplan R, Ritchie A, Meade A, Eisen T, Stockler MR. Patients' preferences for adjuvant sorafenib after resection of renal cell carcinoma in the SORCE trial: what makes it worthwhile? Ann Oncol. 2018 Feb 1;29(2):370-376. doi: 10.1093/annonc/mdx715.
• Fairfax BP, Pratap S, Roberts IS, Collier J, Kaplan R, Meade AM, Ritchie AW, Eisen T, Macaulay VM, Protheroe A. Fatal case of sorafenib-associated idiosyncratic hepatotoxicity in the adjuvant treatment of a patient with renal cell carcinoma. BMC Cancer. 2012 Dec 11;12:590. doi: 10.1186/1471-2407-12-590.

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: June 25, 2007): 1656
• Original Enrollment: Same as current
• Actual Study Completion Date: December 2012
• Actual Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed renal cell carcinoma (RCC)

  • Clear cell or non-clear cell tumors allowed
  • Intermediate- or high-risk disease (Leibovich score 3 to 11)

• Must have undergone surgery for RCC at least 4 weeks but no more than 3 months prior to study entry

  • No evidence of residual macroscopic disease on post-operative CT scan after resection of RCC

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• WBC > 3,400/mm³
• Platelet count > 99,000/mm³
• Creatinine < 2.5 times upper limit of normal (ULN)
• Liver function tests < 1.5 times ULN
• Serum amylase < 1.5 times ULN
• PT/INR < 1.5 times ULN
• PTT < 1.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 9 months after completion of study treatment

• No cardiovascular conditions, including any of the following:

  • Cardiac arrhythmias requiring anti-arrhythmic medication

    • Beta-blockers and digoxin allowed
  • Symptomatic coronary artery disease or ischemia
  • Myocardial infarction within the past 6 months
  • NYHA class II-IV congestive heart failure
• No active clinically serious bacterial or fungal infection
• No known history of HIV infection
• No chronic hepatitis B or C
• No other prior malignancy except carcinoma in situ of the cervix or adequately treated basal cell carcinoma
• No uncontrolled hypertension

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior treatment for RCC other than nephrectomy
• More than 30 days since prior and no other concurrent investigational therapy

• No concurrent medications that have adverse interactions with sorafenib tosylate including, but not limited to, any of the following:

  • Rifampin
  • Grapefruit juice
  • Ritonavir
  • Ketoconazole
  • Itraconazole
  • Hypericum perforatum (St John's wort)
• No concurrent bone marrow transplant or stem cell rescue
• No other concurrent drug that targets angiogenesis, especially VEGF or VEGF receptors (e.g., bevacizumab)
• No other concurrent drug that targets Ras-pathway or EGFR
• No other concurrent anticancer therapy (chemotherapy, immunotherapy, signal transduction inhibition, or hormonal therapy)
• Concurrent non-conventional therapies (e.g., herbs or acupuncture) and vitamin or mineral supplements allowed
• Concurrent bisphosphonates for prophylaxis of osteoporosis allowed

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT00492258
• Other Study ID Numbers: MRC-RE05-SORCE; CDR0000553251 ( Registry Identifier: PDQ (Physician Data Query) ); EUDRACT ID 2006-006079-19; EU-20734; ISRCTN38934710
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Not Provided
• Study Sponsor: Medical Research Council
• Collaborators: Not Provided

Investigators

• Principal Investigator: Timothy Eisen; Cancer Research UK

• PRS Account: National Cancer Institute (NCI)
• Verification Date: April 2008