Pre-Operative Administration of Sorafenib in Patients With Metastatic Renal Cell Carcinoma Undergoing Kidney Removal - Full Text View

Sponsors and Collaborators:	University Health Network, Toronto Bayer
Information provided by:	University Health Network, Toronto
ClinicalTrials.gov Identifier:	NCT00480389

Purpose

The purpose of this study is to see if preoperative administration of Sorafenib reduces the size of the primary kidney tumour in patients with metastatic disease undergoing cytoreductive surgery.

The study will also assess the safety of preoperative Sorafenib.

The study drug, Sorafenib, will be given to patients preoperatively for 12 weeks. After a 1 week washout period the patient will then have their nephrectomy (kidney removed). Approximately 6 weeks following their nephrectomy, patients will resume on study drug until disease progression.

Condition	Intervention	Phase
Renal Cell Carcinoma Metastatic Disease	Drug: Sorafenib tosylate	Phase II

MedlinePlus related topics: Cancer

Drug Information available for: Sorafenib Sorafenib tosylate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Pre-Operative Administration of Sorafenib in Patients With Metastatic Renal Cell Carcinoma Undergoing Cytoreductive Nephrectomy

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:

To measure primary pathological response data and determine if it relates with time to progression [ Time Frame: 12 weeks- 2 years ] [ Designated as safety issue: No ]
Safety of preoperative Sorafenib will be assessed. [ Time Frame: 13 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Tumour vascularity. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Immunohistochemistry will be used to assess the effects of Sorafenib on angiogenic and tumorigenic promoters. Signals from VEGFR2, PDGF-alpha, c-KIT, Flt-3, CAIX and Raf-1 will be assessed. [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]
A DNA microarray will be used for gene expression profiling of the tissue harvested at biopsy and surgery. [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	May 2007
Estimated Study Completion Date:	May 2010
Estimated Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: Sorafenib tosylate Starting dose: 400 mg (2x200mg tablets) BID (total= 800mg/day) taken orally. The dose can be adjusted as per investigator if required due to toxicity (ex. 200mg BID, 200mg QD). Study drug is taken for 12 weeks preoperatively. Patients restart on study drug 6 weeks postoperatively and continue until progression or unacceptable toxicity occurs.

Detailed Description:

This is a single centre, non-randomized, open label one arm pilot study of Sorafenib 400 mg twice daily given for 12 weeks preoperatively in patients with advanced metastatic kidney cancer scheduled for cytoreductive surgery. Patients will be fully staged for disease progression with Brain MRI, CT, whole body Bone Scans, Kidney ultrasound and biopsy. Additionally, patients' cardiac status will be evaluated pre-enrolment with an ECG and MUGA Scan. Once enrolled into the study, patients will have clinic visits on weeks 2, 8 and 12 for monitoring visits with vital signs and adverse event recording plus blood evaluations for hematology and chemistry. Patients will be called on weeks 3,5,6,7,9,10 and 11 to determine any changes in health status. Surgery will occur at week 13, after a one week washout from study drug. Patients will resume on study drug 6 weeks post operatively (or later, if wound is not completely healed). Patients will continue on study drug and will be monitored every 4 weeks until disease progression, as determined by bone imaging and CT.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Biopsy proven RCC with a component of clear cell type histology
Patients must have confirmed metastatic disease
Candidate for cytoreductive nephrectomy
Adequate organ function as defined by:
- AST or ALT less than or equal to 2.5 times the upper limit of normal
- Bilirubin less than or equal to 1.5 times the upper limit of normal
- Absolute neutrophil count (ANC) greater than or equal to 1500/mL
- Platelets greater than or equal to 100,000/mL
- Hemoglobin greater than or equal to 9.0 g/dL
- Serum calcium less than or equal to 12.0 mg/dL
- Serum creatinine less than or equal to 1.5 x CL-ULN
Male or female, 18 years of age or older
Women of childbearing potential must NOT be pregnant (as confirmed by a negative pregnancy test)
ECOG performance status 0 or 1 (see appendix 1 for ECOG performance status)
Signed informed consent form indicating that the patient or acceptable representative has been informed of all parts of the trial prior to enrollment
Willingness and ability to comply with study procedures

Exclusion Criteria:

Presence of brain metastases during screening period
Known hypersensitivity to Sorafenib
Women who are breast-feeding
Severe psychiatric or medical illness that may interfere with compliance with the study protocol or follow-up as deemed by the investigator
History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension.
HIV-positive patients

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00480389

Contacts

Contact: Keri L Durrant, BSc. CCRP	416-946-4501 ext 3431	Keri.Durrant@uhn.on.ca
Contact: Karen Hersey, RN	416-946-2155	Karen.Hersey@uhn.on.ca

Locations

Canada, Ontario
Princess Margaret Hospital, University Health Network	Recruiting
Toronto, Ontario, Canada, M5G 2M9

Sponsors and Collaborators

University Health Network, Toronto

Bayer

Investigators

Principal Investigator:

Antonio Finelli, MD,MSc,FRCSC

University Health Network, Toronto

More Information

Publications:

Flanigan RC. Debulking nephrectomy in metastatic renal cancer. Clin Cancer Res. 2004 Sep 15;10(18 Pt 2):6335S-41S. Review.

Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol. 1999 Aug;17(8):2530-40.

Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, Caton JR Jr, Munshi N, Crawford ED. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001 Dec 6;345(23):1655-9.

Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R; European Organisation for Research and Treatment of Cancer (EORTC) Genitourinary Group. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet. 2001 Sep 22;358(9286):966-70.

Eisen et al. Randomized phase III trial of sorafenib in advanced RCC: Impact of crossover on survival. ASCO Atlanta June 2006. Abs 4524

Responsible Party:	University Health Network ( Dr. Antonio Finelli/Urologic Oncologist )
Study ID Numbers:	06-0655-C
Study First Received:	May 28, 2007
Last Updated:	November 7, 2008
ClinicalTrials.gov Identifier:	NCT00480389
Health Authority:	Canada: Health Canada

Keywords provided by University Health Network, Toronto:

Clear cell Renal cell carcinoma
Metastatic
Sorafenib tosylate
Preoperative treatment

Study placed in the following topic categories:

Urogenital Neoplasms
Renal cancer
Urologic Neoplasms
Kidney cancer
Carcinoma
Urologic Diseases
Kidney Neoplasms
Neoplasm Metastasis

Carcinoma, Renal Cell
Kidney Diseases
Adenocarcinoma
Clear cell renal cell carcinoma
Sorafenib
Urinary tract neoplasm
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplastic Processes
Neoplasms
Pathologic Processes
Neoplasms by Site
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action

Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 13, 2009