Clinical trial NCT00480389: Pre-operative Administration of Sorafenib in Patients With Metastatic Renal Cell Carcinoma Undergoing Kidney Removal
Official title: Pre-operative Administration of Sorafenib in Patients With Metastatic Renal Cell Carcinoma Undergoing Cytoreductive Nephrectomy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Renal Cell Carcinoma
Metastatic Disease
Keywords: Clear cell Renal cell carcinoma
Metastatic
Sorafenib tosylate
Preoperative treatment
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2007-05-30
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: To measure primary pathological response data and determine if it relates with time to progression
timeFrame: 12 weeks- 2 years
measure: Safety of preoperative Sorafenib will be assessed.
timeFrame: 13 weeks
Secondary outcomes:
measure: Tumour vascularity.
timeFrame: 12 weeks
measure: 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.
timeFrame: 13 weeks
measure: A DNA microarray will be used for gene expression profiling of the tissue harvested at biopsy and surgery.
timeFrame: 13 weeks
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Hospital, University Health Network
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Antonio Finelli, MD,MSc,FRCSC
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Eisen et al. Randomized phase III trial of sorafenib in advanced RCC: Impact of crossover on survival. ASCO Atlanta June 2006. Abs 4524