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

December 7, 2015 updated by: University Health Network, Toronto

Pre-operative Administration of Sorafenib in Patients With Metastatic Renal Cell Carcinoma Undergoing Cytoreductive Nephrectomy

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: 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.
Other Names:
  • Nexavar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To measure primary pathological response data and determine if it relates with time to progression
Time Frame: 12 weeks- 2 years
12 weeks- 2 years
Safety of preoperative Sorafenib will be assessed.
Time Frame: 13 weeks
13 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Tumour vascularity.
Time Frame: 12 weeks
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.
Time Frame: 13 weeks
13 weeks
A DNA microarray will be used for gene expression profiling of the tissue harvested at biopsy and surgery.
Time Frame: 13 weeks
13 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Collaborators

Bayer

Investigators

  • Principal Investigator: Antonio Finelli, MD,MSc,FRCSC, University Health Network, Toronto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2007

Primary Completion (Actual)

October 1, 2012

Study Completion (Actual)

March 1, 2013

Study Registration Dates

First Submitted

May 28, 2007

First Submitted That Met QC Criteria

May 29, 2007

First Posted (Estimate)

May 30, 2007

Study Record Updates

Last Update Posted (Estimate)

December 9, 2015

Last Update Submitted That Met QC Criteria

December 7, 2015

Last Verified

December 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06-0655-C

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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