Study of BAY43-9006 in Patients With Unresectable and/or Metastatic Renal Cell Cancer

Carcinoma, Renal Cell Clinical Trial

Official title:

A Phase III Randomized Study of BAY43-9006 in Patients With Unresectable and/or Metastatic Renal Cell Cancer.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00073307
• Other study ID #: 11213
• Status: Completed
• Phase: Phase 3
• First received: November 19, 2003
• Last updated: January 8, 2014
• Start date: November 2003
• Est. completion date: April 2010

Study information

• Verified date: January 2014
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate safety, efficacy (including quality of life), and pharmacokinetics of BAY43-9006 when added to Best Supportive Care in patients with unresectable and/or metastatic renal cell cancer, who have received one prior systemic regimen for advanced disease.

Description:

Overall Survival (OS), Patient-reported outcome (PRO)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 903
• Est. completion date: April 2010
• Est. primary completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with unresectable and/or metastatic, measurable renal cell carcinoma histologically or cytologically documented

• Patients must have had one prior systemic therapy for advanced disease, which was completed at least 30 days but no longer than 8 months prior to randomization

• Patients who have at least one uni-dimensional measurable lesion by CT-scan or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST)

• Patients who have an Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1

• Patients who have adequate coagulation, liver and kidney functions

Exclusion Criteria:

• Patients with rare subtypes of renal cell carcinoma (RCC) such as pure papillary cell tumors, mixed tumor containing predominantly sarcomatoid cells, Bellini carcinoma, medullary carcinoma, or chromophobe oncocytic tumors

• Previous malignancy (except for cervical carcinoma in situ, adequately treated basal cell carcinoma,or superficial bladder tumors, or other malignancies curatively treated > 2 years prior to entry

• Cardiac arrhythmias requiring anti-arrhythmics, symptomatic coronary artery disease or ischemia or congestive heart failure

• Patients with a history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C

• Patients with a history or presence of metastatic brain or meningeal tumors

• Patients with seizure disorder requiring medication (such as anti-epileptics)

• History of organ allograft or bone marrow transplant of stem cell rescue

• Patients who are pregnant or breast-feeding Women of childbearing potential must have a negative pregnancy test prior to drug administration. Both men and women enrolled in this trial must use adequate birth control

• Patients who have three or more of the following:

• ECOG performance status greater than or equal to 2,

• Abnormally high lactate dehydrogenase,

• Abnormally high serum hemoglobin,

• Abnormally high corrected serum calcium,

• Absence of prior nephrectomy

• Excluded therapies and medications, previous and concomitant:

• Concurrent anti-cancer chemotherapy, immunotherapy or hormonal therapy except biphosphonates

• Significant surgery with 4 weeks of start of study

• Investigational drug therapy during or within 30 days

• Concomitant treatment with rifampin or St. John's Wort

• Prior use of Raf-kinase inhibitors (RKI), MEK or Farnesyl transferase inhibitors

• Prior use of Bevacizumab, and all other drugs (investigational or licensed) that target VEGF/VEGF receptors

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Renal Cell

Intervention

Drug:
• Sorafenib (Nexavar, BAY43-9006)
Multi Kinase Inhibitor
• Placebo
Placebo

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Bayer	Onyx Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Chile,  France,  Germany,  Hungary,  Israel,  Italy,  Netherlands,  Poland,  Russian Federation,  South Africa,  Spain,  Ukraine,  United Kingdom, 

References & Publications (11)

Antoun S, Birdsell L, Sawyer MB, Venner P, Escudier B, Baracos VE. Association of skeletal muscle wasting with treatment with sorafenib in patients with advanced renal cell carcinoma: results from a placebo-controlled study. J Clin Oncol. 2010 Feb 20;28(6 — View Citation

Bellmunt J, Eisen T, Fishman M, Quinn D. Experience with sorafenib and adverse event management. Crit Rev Oncol Hematol. 2011 Apr;78(1):24-32. doi: 10.1016/j.critrevonc.2010.03.006. Epub 2010 Apr 18. Review. — View Citation

Bukowski R, Cella D, Gondek K, Escudier B; Sorafenib TARGETs Clinical Trial Group. Effects of sorafenib on symptoms and quality of life: results from a large randomized placebo-controlled study in renal cancer. Am J Clin Oncol. 2007 Jun;30(3):220-7. — View Citation

Eisen T, Oudard S, Szczylik C, Gravis G, Heinzer H, Middleton R, Cihon F, Anderson S, Shah S, Bukowski R, Escudier B; TARGET Study Group. Sorafenib for older patients with renal cell carcinoma: subset analysis from a randomized trial. J Natl Cancer Inst. — View Citation

Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM; TARGET Study Group. Sorafenib in advanced clear-ce — View Citation

Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Staehler M, Negrier S, Chevreau C, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Anderson S, Hofilena G, Shan M, Pena C, Lathia C, Bukowski RM. Sorafenib for treatment of renal cell carcinoma: Fin — View Citation

Kane RC, Farrell AT, Saber H, Tang S, Williams G, Jee JM, Liang C, Booth B, Chidambaram N, Morse D, Sridhara R, Garvey P, Justice R, Pazdur R. Sorafenib for the treatment of advanced renal cell carcinoma. Clin Cancer Res. 2006 Dec 15;12(24):7271-8. Review — View Citation

Lamuraglia M, Escudier B, Chami L, Schwartz B, Leclère J, Roche A, Lassau N. To predict progression-free survival and overall survival in metastatic renal cancer treated with sorafenib: pilot study using dynamic contrast-enhanced Doppler ultrasound. Eur J — View Citation

Massard C, Zonierek J, Gross-Goupil M, Fizazi K, Szczylik C, Escudier B. Incidence of brain metastases in renal cell carcinoma treated with sorafenib. Ann Oncol. 2010 May;21(5):1027-31. doi: 10.1093/annonc/mdp411. Epub 2009 Oct 22. — View Citation

Negrier S, Jäger E, Porta C, McDermott D, Moore M, Bellmunt J, Anderson S, Cihon F, Lewis J, Escudier B, Bukowski R. Efficacy and safety of sorafenib in patients with advanced renal cell carcinoma with and without prior cytokine therapy, a subanalysis of — View Citation

Peña C, Lathia C, Shan M, Escudier B, Bukowski RM. Biomarkers predicting outcome in patients with advanced renal cell carcinoma: Results from sorafenib phase III Treatment Approaches in Renal Cancer Global Evaluation Trial. Clin Cancer Res. 2010 Oct 1;16( — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Final Overall Survival (OS) - Primary Analysis in the ITT (Intent To Treat) Population	Overall survival determined as the time (days) from the date of randomization at start of study to the date of death, due to any cause. Outcome measure was assessed regularly, i.e. every 3 weeks for the first 24 weeks during treatment and every 4 weeks thereafter and approximately every 3 months during post-treatment.	From start of randomization of the first subject (1Dec2003) until the data cut-off (8Sep2006) for the final OS analysis, approximately 33 months later	No
Primary	Final Overall Survival - Secondary Analysis (Placebo Data Censored at 30June2005) in the ITT Population	Overall survival determined as the time (days) from the date of randomization at start of study to the date of death, due to any cause. Outcome measure was assessed regularly, i.e. every 3 weeks for the first 24 weeks during treatment and every 4 weeks thereafter and approximately every 3 months during post-treatment.	From start of randomization of the first subject (1Dec2003) until the data cut-off (8Sep2006) for the final OS analysis, approximately 33 months later	No
Secondary	Final Progression-Free Survival (PFS) - Independent Radiological Review	PFS determined as the time (days) from the date of randomization at start of study to the actual date of disease progression (PD) (radiological or clinical) or death due to any cause, if death occurred before PD. Outcome measure was assessed approximately every 8 weeks using RECIST v1.0 criteria by independent radiologic review. Radiological PD defined as at least 20% increase in sum of longest diameter (LD) of measured lesions taking as reference smallest sum LD recorded since treatment started or appearance of new lesions.	From start of randomization of the first subject (1Dec2003) until the data cut-off (28Jan2005), approximately 14 months later, tumors assessed every 8 weeks.	No
Secondary	Best Overall Response - Independent Radiological Review	Best overall response was determined according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 by independent radiologic review. Categories: complete response (CR, tumor disappears), partial response (PR, sum of lesion sizes decreased), stable disease (SD, steady state of disease), progressive disease (PD, sum of lesion sizes increased) and not evaluated.	From start of randomization of the first subject (1Dec2003) until the data cut-off (28Jan2005), approximately 14 months later, tumors assessed every 8 weeks.	No
Secondary	Health-related Quality of Life (HRQOL) by FKSI-10 (Functional Assessment of General Therapy Kidney Symptom Index 10) Assessment	Primary Analysis for FKSI-10 patient-reported outcome (PRO) measure defined as longitudinal analysis of mean score over the first 5 treatment cycles. FKSI-10 patient responses for each question range from "0=not at all" to "4=very much" and after reverse coding the range of values for FKSI-10 total score is from 0 to 40; higher score represents better HRQOL.	From start of randomization of the first subject (1Dec2003) until the data cut-off (31May2005), approximately 18 months later, PRO data collected at Day 1 of each cycle and end of treatment.	No
Secondary	Health-related Quality of Life (HRQOL) by Physical Well-Being (PWB) Score of the FACT-G (Functional Assessment of Cancer Therapy-General Version) Assessment	Primary Analysis for FACT-G (using PWB score) patient-reported outcome (PRO) measure defined as longitudinal analysis of mean score over the first 5 treatment cycles. FACT-G (PWB score) patient responses for each question range from "0=not at all" to "4=very much" and after reverse coding the total FACT-G (PWB score) range of values is from 0 to 28; higher score represents better HRQOL.	From start of randomization of the first subject (1Dec2003) until the data cut-off (31May2005), approximately 18 months later, PRO data collected at Day 1 of each cycle and end of treatment.	No

External Links

•   Click here and search for drug information provided by the FDA.
•   Click here and search for information on any recalls, market or product safety alerts by the FDA which might have occurred with this product.