Pre-operative Administration of Sorafenib in Patients With Metastatic Renal Cell Carcinoma Undergoing Kidney Removal

NCT ID: NCT00480389

Last Updated: 2015-12-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2013-03-31

Brief Summary

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.

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.

Conditions

Renal Cell Carcinoma; Metastatic Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sorafenib

All patients on study will be accrued to this arm. Sorafenib (200 mg tablets x 2) will be administered orally twice a day for 12 weeks (full daily dose of 800 mg). Patient visits for safety will be conducted at least every 4 weeks. Sorafenib dose reductions for drug-related toxicity will be applied based on considerable prior clinical experience. Surgery will be performed at the completion of the 13th week, allowing for a one-week "washout" period. Sorafenib will be continued post operatively (around 6 weeks post surgery or when complete wound healing has occurred) until patient progresses or unacceptable toxicity occurs.

Group Type: EXPERIMENTAL

Sorafenib

Intervention Type: DRUG

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.

Interventions

Sorafenib

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.

Intervention Type: DRUG

Other Intervention Names

Nexavar

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antonio Finelli, MD,MSc,FRCSC

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

Princess Margaret Hospital, University Health Network

Toronto, Ontario, Canada

Countries

Canada

References

Flanigan RC. Debulking nephrectomy in metastatic renal cancer. Clin Cancer Res. 2004 Sep 15;10(18 Pt 2):6335S-41S. doi: 10.1158/1078-0432.CCR-sup-040026.

Reference Type: BACKGROUND

PMID: 15448027 (View on PubMed)

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. doi: 10.1200/JCO.1999.17.8.2530.

Reference Type: BACKGROUND

PMID: 10561319 (View on PubMed)

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. doi: 10.1056/NEJMoa003013.

Reference Type: BACKGROUND

PMID: 11759643 (View on PubMed)

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. doi: 10.1016/s0140-6736(01)06103-7.

Reference Type: BACKGROUND

PMID: 11583750 (View on PubMed)

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

Reference Type: BACKGROUND

Other Identifiers

06-0655-C

Identifier Type: -

Identifier Source: org_study_id