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

Primary Purpose

Renal Cell Carcinoma, Metastatic Disease

Status

Completed

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Sorafenib

About this trial

This is an interventional treatment trial for Renal Cell Carcinoma focused on measuring Clear cell Renal cell carcinoma, Metastatic, Sorafenib tosylate, Preoperative treatment

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Princess Margaret Hospital, University Health Network

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sorafenib

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Safety of preoperative Sorafenib will be assessed.

Secondary Outcome Measures

Tumour vascularity.

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.

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

Full Information

NCT ID

NCT00480389

First Posted

May 28, 2007

Last Updated

December 7, 2015

Sponsor

University Health Network, Toronto

Collaborators

Bayer

1. Study Identification

Unique Protocol Identification Number

NCT00480389

Brief Title

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

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Completed

Study Start Date

May 2007 (undefined)

Primary Completion Date

October 2012 (Actual)

Study Completion Date

March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Health Network, Toronto

Collaborators

Bayer

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Renal Cell Carcinoma, Metastatic Disease

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

19 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sorafenib

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Sorafenib

Other Intervention Name(s)

Nexavar

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Time Frame

12 weeks- 2 years

Title

Safety of preoperative Sorafenib will be assessed.

Time Frame

13 weeks

Secondary Outcome Measure Information:

Title

Tumour vascularity.

Time Frame

12 weeks

Title

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

Title

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

Time Frame

13 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Antonio Finelli, MD,MSc,FRCSC

Organizational Affiliation

University Health Network, Toronto

Official's Role

Principal Investigator

Facility Information:

Facility Name

Princess Margaret Hospital, University Health Network

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 2M9

Country

Canada

12. IPD Sharing Statement

Citations:

PubMed Identifier

15448027

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.

Results Reference

background

PubMed Identifier

10561319

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.

Results Reference

background

PubMed Identifier

11759643

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.

Results Reference

background

PubMed Identifier

11583750

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.

Results Reference

background

Citation

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

Results Reference

background

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

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