Sunitinib Malate Before and After Surgery in Treating Patients With Previously Untreated Metastatic Kidney Cancer

Upfront Sunitinib (SU011248) Therapy Followed by Surgery in Patients With Metastatic Renal Cancer: A Pilot Phase II Study [SuMR]

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.

PURPOSE: This phase II trial is studying how well giving sunitinib malate before and after surgery works in treating patients with metastatic kidney cancer.

Study Overview

• Status: Completed
• Conditions: Kidney Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Procedure: therapeutic conventional surgery; Procedure: adjuvant therapy; Procedure: neoadjuvant therapy; Drug: sunitinib malate

Detailed Description

OBJECTIVES:

Primary

• Determine if neoadjuvant sunitinib malate can achieve a clinical benefit of 70% or more to the primary renal tumor prior to surgery and adjuvant sunitinib malate in patients with metastatic renal cancer.

Secondary

• Determine the time to radiological progression in these patients.
• Determine the overall survival of these patients.
• Determine the proportion of patients suitable for nephrectomy after neoadjuvant sunitinib malate.
• Determine the translational endpoints.

OUTLINE: Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 6 weeks for 3 courses. Approximately 2 weeks later, patients undergo a standard radical nephrectomy with lymph node dissection. Beginning at least 2 weeks after surgery, patients receive oral sunitinib malate on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Blood and tissue samples may be collected periodically for laboratory studies.

After completion of study treatment, patients are followed every 2 months.

• Study Type: Interventional
• Enrollment (Anticipated): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • London, England, United Kingdom, EC1M 6BQ
      • Orchid Clinical Trials Group at Barts and the London School of Medicine and Dentistry

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

  • Measurable metastatic disease on CT/MRI imaging
  • Patients with suspicion of renal cancer on radiology must have a biopsy to confirm diagnosis of clear cell disease
• No prior therapy for renal cancer
• Judged by the treating physician to have the potential to derive clinical benefit from this treatment

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Absolute neutrophil count ≥ 1 x 10^9/L (without growth factor support)
• Platelet count ≥ 75 x 10^9/L
• Total bilirubin ≤ 2 times upper limit of normal (ULN) (except for patients with Gilbert disease)
• Serum creatinine ≤ 2 times ULN
• Serum transaminases < 5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 28 days after completion of study therapy
• Willing and able to comply with scheduled visits, treatment plan, and laboratory tests and other study procedures
• No congestive heart failure, myocardial infarction, or coronary artery bypass graft within the past 6 months, or ongoing severe or unstable arrhythmia requiring medication
• No other severe acute or chronic medical or psychiatric condition, or abnormal laboratory results that would impart, in the judgement of the investigator, excess risk associated with study participation or study drug administration or would make the patient inappropriate for entry into this study

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 7 days since prior and no concurrent potent CYP3A inhibitors, including any of the following:

  • Ketoconazole
  • Itraconazole
  • Clarithromycin
  • Erythromycin
  • Diltiazem
  • Verapamil
  • Delavirdine
  • Indinavir
  • Saquinavir
  • Ritonavir
  • Atazanavir
  • Nelfinavir

• At least 12 days since prior and no concurrent potent CYP3A inducers, including any of the following:

  • Rifampin
  • Rifabutin
  • Carbamazepine
  • Phenobarbital
  • Phenytoin
  • St. John's wort
  • Efavirenz
  • Tipranavir
• Concurrent radiotherapy allowed provided sunitinib malate is stopped one day before and resumed one day after radiotherapy
• Concurrent coumarin-derivative anticoagulants (e.g., warfarin) allowed (≤ 2 mg/day) for prophylaxis of thrombosis
• No concurrent treatment with a drug having proarrhythmic potential (i.e., terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, or flecainide)
• No other concurrent investigational drug or participation in another clinical trial (unless approved by the sponsor)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Neoadjuvant sunitinib malate achieving a clinical benefit of ≥ 70%

Secondary Outcome Measures

Outcome Measure
Overall survival
Time to radiological progression
Proportion of patients suitable for nephrectomy after neoadjuvant sunitinib malate

Collaborators and Investigators

• Sponsor: Barts and the London School of Medicine and Dentistry
• Investigators: Principal Investigator: Thomas Powles, MD, MRCP, Barts and The London School of Medicine and Dentistry

Publications and helpful links

General Publications

• Powles T, Chowdhury S, Bower M, Saunders N, Lim L, Shamash J, Sarwar N, Sadev A, Peters J, Green J, Boleti K, Augwal S. The effect of sunitinib on immune subsets in metastatic clear cell renal cancer. Urol Int. 2011;86(1):53-9. doi: 10.1159/000319498. Epub 2010 Oct 26.
• Stewart GD, Powles T, Van Neste C, Meynert A, O'Mahony F, Laird A, Deforce D, Van Nieuwerburgh F, Trooskens G, Van Criekinge W, De Meyer T, Harrison DJ. Dynamic epigenetic changes to VHL occur with sunitinib in metastatic clear cell renal cancer. Oncotarget. 2016 May 3;7(18):25241-50. doi: 10.18632/oncotarget.8308.
• Stewart GD, O'Mahony FC, Laird A, Rashid S, Martin SA, Eory L, Lubbock AL, Nanda J, O'Donnell M, Mackay A, Mullen P, McNeill SA, Riddick AC, Aitchison M, Berney D, Bex A, Overton IM, Harrison DJ, Powles T. Carbonic anhydrase 9 expression increases with vascular endothelial growth factor-targeted therapy and is predictive of outcome in metastatic clear cell renal cancer. Eur Urol. 2014 Nov;66(5):956-63. doi: 10.1016/j.eururo.2014.04.007. Epub 2014 May 10.
• Shaw GL, Hussain M, Nair R, Bycroft J, Beltran L, Green JS, Powles T, Peters JL. Performing cytoreductive nephrectomy following targeted sunitinib therapy for metastatic renal cell carcinoma: a surgical perspective. Urol Int. 2012;89(1):83-8. doi: 10.1159/000338057. Epub 2012 May 16.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: December 1, 2009
• First Submitted That Met QC Criteria: December 1, 2009
• First Posted (Estimate): December 2, 2009

Study Record Updates

• Last Update Posted (Estimate): August 12, 2013
• Last Update Submitted That Met QC Criteria: August 9, 2013
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: stage IV 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; 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: OCTG-SuMR; CDR0000660317 (Registry Identifier: PDQ (Physician Data Query)); EUDRACT-2006-004511-21; REDA-4911; MREC-07/Q0603/58; PFIZER-OCTG-SuMR