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

Study Overview
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Brief Summary
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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.

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

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

Conditions
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Carcinoma, Renal Cell

Intervention / Treatment
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* Drug: Sorafenib (Nexavar, BAY43-9006)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sorafenib (Nexavar, BAY43-9006)<br>Sorafenib was to be orally administered as 2 x 200 mg tablets bid (twice daily). Dose modification due to toxicity was permitted. | Drug: Sorafenib (Nexavar, BAY43-9006)<br>* Multi Kinase Inhibitor<br>|
| Placebo Comparator: Placebo<br>Placebo tablets matching in appearance were to be orally administered twice a day. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| 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. | 
| 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. | 
| 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal Cell Cancer (RCC), Cancer