Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients With Metastatic Kidney Cancer (SURTIME)

• ClinicalTrials.gov Identifier: NCT01099423
• Recruitment Status: Unknown
• First Posted: April 7, 2010
• Last Update Posted: February 8, 2017
• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Collaborators: Wales Cancer Trials Unit; Canadian Urologic Oncology Group; Institute of Cancer Research, United Kingdom
• Information provided by (Responsible Party): European Organisation for Research and Treatment of Cancer - EORTC

Tracking Information

• First Submitted Date: April 6, 2010
• First Posted Date: April 7, 2010
• Last Update Posted Date: February 8, 2017
• Actual Study Start Date: April 2010
• Actual Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 6, 2010): Overall progression-free survival
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 6, 2010)

• Overall survival
• Morbidity
• Overall response to treatment in the deferred nephrectomy arm including the proportion of patients who become unresectable
• Effect of nephrectomy on early progression in both arms

• 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: Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients With Metastatic Kidney Cancer
• Official Title: Randomized Phase III Trial Comparing Immediate Versus Deferred Nephrectomy in Patients With Synchronous Metastatic Renal Cell Carcinoma

Brief Summary

RATIONALE: Sunitinib malate 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 sunitinib malate before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving sunitinib malate after surgery may kill any tumor cells that remain after surgery. It is not yet known whether undergoing immediate surgery or surgery after sunitinib malate is more effective in treating patients with metastatic kidney cancer.

PURPOSE: This randomized phase III trial is studying immediate surgery to see how well it works compared with surgery after sunitinib malate in treating patients with metastatic kidney cancer.

Detailed Description

OBJECTIVES:

• To determine if immediate versus deferred nephrectomy has an effect on disease control in patients with resectable, synchronous, metastatic renal cell carcinoma treated with sunitinib malate.
• To identify potential response criteria based on histopathology and molecular research on tumor tissue.

OUTLINE: This is a multicenter study. Patients are stratified according to WHO performance status (0 vs 1), number of metastatic sites (1 vs 2 or more), and institution. Patients are randomized to 1 of 2 treatment arms.

• Arm I (immediate nephrectomy): Patients undergo cytoreductive nephrectomy. Beginning 4 weeks after surgery, patients receive oral sunitinib malate once daily on days 1-28. Treatment with sunitinib malate repeats every 6 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
• Arm II (deferred nephrectomy): Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. About 1 day after completion of sunitinib malate, patients undergo cytoreductive nephrectomy. Patients then receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.

Some patients undergo tumor tissue collection at baseline and at time of surgery to assess possible differences in gene expression. Patients also undergo blood sample collection periodically to evaluate the potential impact of serum proteins on the clinical outcome. Samples are then stored for future studies.

After completion of study treatment, patients are followed periodically.

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

Intervention

• Procedure: timing of surgery
• Genetic: gene expression analysis
• Other: biologic sample preservation procedure
• Other: laboratory biomarker analysis
• Procedure: therapeutic conventional surgery

Study Arms

• Active Comparator: Immediate nephrectomy
  Surgery followed by Sunitinib
  Interventions:

  • Genetic: gene expression analysis
  • Other: biologic sample preservation procedure
  • Other: laboratory biomarker analysis
  • Procedure: therapeutic conventional surgery
• Experimental: Deferred nephrectomy
  Sunitinib (3 cycles) followed by surgery followed by Sunitinib
  Interventions:

  • Procedure: timing of surgery
  • Genetic: gene expression analysis
  • Other: biologic sample preservation procedure
  • Other: laboratory biomarker analysis

Publications *

• Bex A, Mulders P, Jewett M, Wagstaff J, van Thienen JV, Blank CU, van Velthoven R, Del Pilar Laguna M, Wood L, van Melick HHE, Aarts MJ, Lattouf JB, Powles T, de Jong Md PhD IJ, Rottey S, Tombal B, Marreaud S, Collette S, Collette L, Haanen J. Comparison of Immediate vs Deferred Cytoreductive Nephrectomy in Patients With Synchronous Metastatic Renal Cell Carcinoma Receiving Sunitinib: The SURTIME Randomized Clinical Trial. JAMA Oncol. 2019 Feb 1;5(2):164-170. doi: 10.1001/jamaoncol.2018.5543. Erratum in: JAMA Oncol. 2019 Feb 1;5(2):271.
• León L, García-Figueiras R, Suárez C, Arjonilla A, Puente J, Vargas B, Méndez Vidal MJ, Sebastiá C. Recommendations for the clinical and radiological evaluation of response to treatment in metastatic renal cell cancer. Target Oncol. 2014 Mar;9(1):9-24. doi: 10.1007/s11523-013-0304-7. Epub 2013 Dec 12. Review. Erratum in: Target Oncol. 2014 Jun;9(2):181. García-Figueras, Roberto [corrected to García-Figueiras, Roberto].
• Winquist E, Rodrigues G. Open clinical uro-oncology trials in Canada. Can J Urol. 2012 Dec;19(6):6587-91.

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: July 11, 2016): 99
• Original Estimated Enrollment (submitted: April 6, 2010): 458
• Estimated Study Completion Date: May 2017
• Actual Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed renal cell cancer (RCC)

  • Clear-cell subtype with a resectable asymptomatic in situ primary

    • Asymptomatic primary is defined as the absence of symptoms* which can be exclusively assigned to the primary tumor such as flank pain and/or gross hematuria necessitating blood transfusion NOTE: *Para-neoplastic symptoms cannot be assigned to the primary tumor alone in metastatic disease, they are not included in this definition.
    • No symptomatic primary tumor necessitating nephrectomy

• Resectable primary tumor

  • Bulky locoregional lymph node metastases larger than the primary tumor allowed provided resectability of the lymph nodes is surgically feasible

• Metastatic RCC

  • Distant metastases are not completely resectable at the time of surgery or during an additional intervention
  • No multiple distant lesions at one site
  • No bone-only metastases
• Measurable disease, both primary and metastatic, according to RECIST 1.1 criteria
• Planning to receive sunitinib malate as background therapy

• Patients with > 3 of the following surgical risk factors are not eligible:

  • Serum albumin CTCAE v 4.0 grade 2 or worse
  • Serum LDH > 1.5 times upper limit of normal
  • Liver metastases
  • Symptoms at presentation due to metastases
  • Retroperitoneal lymph node involvement
  • Supra-diaphragmatic lymph node involvement
  • Clinical stage T3 or T4 disease
• No clinical signs of CNS involvement

PATIENT CHARACTERISTICS:

• See Disease Characteristics
• WHO performance status 0-1
• Life expectancy > 3 months
• WBC > 3.0 x 10^9/L
• Platelet count > 100 x 10^9/L
• Hemoglobin > 10.0 g/dL
• PT/PTT or INR ≤ 1.2 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• ALT ≤ 2.5 times ULN (≤ 5 times ULN if liver lesions)
• Serum calcium < 10.0 mg/dL
• Calculated or measured creatinine clearance > 30 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception 2 weeks before and during study treatment
• LVEF normal by MUGA scan or ECHO
• 12-lead ECG normal
• No serious cardiac illness (myocardial infarction and/or treatable or untreatable angina pectoris not responding to treatment) within the past 12 months
• No uncontrolled, high BP (≥ 150/100 mm Hg) despite optimal medical therapy
• No current pulmonary disease
• No active or uncontrolled infections, serious illnesses, malabsorption syndrome, or medical conditions, including patients with a history of chronic alcohol abuse, hepatitis, HIV, and/or cirrhosis
• No malignancies within the past 5 years except renal cell carcinoma, basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, resected incidental prostate cancer staged pT2 with Gleason Score ≤ 6 and postoperative PSA < 0.5 ng/mL, or patients with any history of malignancies who are disease-free for more than 5 years
• No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

PRIOR CONCURRENT THERAPY:

• Prior local radiotherapy for bone lesions allowed
• No prior systemic therapy for metastatic RCC
• No prior partial or total nephrectomy
• No concurrent systemic corticosteroid and/or other immunosuppressive systemic therapies
• No concurrent radiotherapy, except palliative radiotherapy
• No concurrent participation in another clinical trial testing treatments for any disease including renal cell carcinoma
• No other concurrent investigational or systemic therapy for metastatic RCC

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 120 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, Italy, Netherlands, United Kingdom

Administrative Information

• NCT Number: NCT01099423
• Other Study ID Numbers: EORTC-30073; EU-21022; PFIZER-EORTC-30073
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
• Study Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

Collaborators

• Wales Cancer Trials Unit
• Canadian Urologic Oncology Group
• Institute of Cancer Research, United Kingdom

Investigators

• Study Chair: Axel Bex; The Netherlands Cancer Institute
• Study Chair: John B.A.G. Haanen; The Netherlands Cancer Institute

• PRS Account: European Organisation for Research and Treatment of Cancer - EORTC
• Verification Date: February 2017