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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2011 by University Health Network, Toronto.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Bayer
Information provided by:
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT00480389
First received: May 28, 2007
Last updated: May 12, 2011
Last verified: May 2011
  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 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pre-operative Administration of Sorafenib in Patients With Metastatic Renal Cell Carcinoma Undergoing Cytoreductive Nephrectomy

Resource links provided by NLM:


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: January 2012
Estimated Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sorafenib
All patients on study will be accrued to this arm.
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.
Other Name: Nexavar

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

Locations
Canada, Ontario
Princess Margaret Hospital, University Health Network
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:
Responsible Party: Dr. Antonio Finelli/Urologic Oncologist, University Health Network
ClinicalTrials.gov Identifier: NCT00480389     History of Changes
Other Study ID Numbers: 06-0655-C
Study First Received: May 28, 2007
Last Updated: May 12, 2011
Health Authority: Canada: Health Canada

Keywords provided by University Health Network, Toronto:
Clear cell Renal cell carcinoma
Metastatic
Sorafenib tosylate
Preoperative treatment

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasm Metastasis
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Neoplastic Processes
Pathologic Processes
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 21, 2013