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

NCT00480389 | Completed Phase 2 DMC

• 1 other identifier: 06-0655-C
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Cell Carcinoma; Metastatic Disease

Keywords

Clear cell Renal cell carcinoma; Metastatic; Sorafenib tosylate; Preoperative treatment

Outcome Measures

Primary Outcomes (2)

• To measure primary pathological response data and determine if it relates with time to progression

  12 weeks- 2 years

• Safety of preoperative Sorafenib will be assessed.

  13 weeks

Secondary Outcomes (3)

• Tumour vascularity.

  12 weeks

• 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.

  13 weeks

• A DNA microarray will be used for gene expression profiling of the tissue harvested at biopsy and surgery.

  13 weeks

Study Arms (1)

Sorafenib

EXPERIMENTAL

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.

Drug: Sorafenib

Interventions

Sorafenib 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.

Also known as: Nexavar

Sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Bayer: collaborator

Study Sites (1)

Princess Margaret Hospital, University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (5)

• 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.

  PMID: 15448027 BACKGROUND

• 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.

  PMID: 10561319 BACKGROUND

• 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.

  PMID: 11759643 BACKGROUND

• 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.

  PMID: 11583750 BACKGROUND

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

  BACKGROUND

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasm Metastasis

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Antonio Finelli, MD,MSc,FRCSC

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2007
• First Posted: May 30, 2007
• Study Start: May 1, 2007
• Primary Completion: October 1, 2012
• Study Completion: March 1, 2013
• Last Updated: December 9, 2015

Record last verified: 2015-12

Locations

CA (1)