Back to resultsPhase III Study of Sorafenib in Patients With Renal Cell Carcinoma (RCC)
Primary Purpose
Carcinoma, Renal Cell
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Sorafenib (Nexavar, BAY43-9006)
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Renal Cell focused on measuring Sorafenib, Nexavar, Metastatic RCC, Renal Cell Carcinoma, Unresectable RCC
Eligibility Criteria
Inclusion Criteria:
- Patients who have a life expectancy of at least 12 weeks
- Patients, who suffer from unresectable and/or metastatic, measurable RCC histologically or cytologically documented. Patients with rare subtypes of RCC such as pure papillary cell tumor, mixed tumor containing predominantly sarcomatoid cells, Bellini carcinoma, medullary carcinoma, or chromophobe oncocytic tumors are excluded from study participation.
- Patients who have received not more than one prior systemic therapy for advanced disease which was completed at least 30 days prior to the first dose of study medication.
- Patients who have at least one uni-dimensional measurable lesion by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI) according to Response Evaluation Criteria in Solid Tumours (RECIST)
- Patients with "Intermediate" or "low" risk per the Motzer score
- Patients who have an Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1
- Adequate bone marrow, liver and renal function at screening as assessed by the following:
- Total bilirubin < 1.5 x the upper limit of normal.
- Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer).
Amylase and lipase < 1.5 x the upper limit of normal.
- Serum creatinine < 2.0 x the upper limit of normal.
- Prothrombin Time (PT) or International Normalized Ratio (INR) and Partial Thromboplastin Time (PTT) < 1.5 x upper limit of normal
Exclusion Criteria:
- Previous or concurrent cancer that is distinct in primary sit or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, adequately treated basal cell carcinoma, superficial bladder tumors [Ta (Noninvasive papillary carcinoma), Tis (Carcinoma in situ: "flat tumor") and T1 (Tumor invades subepithelial connective tissue)] or any cancer curatively treated > 3 years prior to study entry)
- Patients who completed their prior systemic treatment regimen less than 30 days
- Cardiac arrhythmias requiring anti-arrhythmic (excluding beta blockers or digoxin), symptomatic coronary artery disease or ischemia
- Active clinically serious bacterial or fungal infections
- Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C requiring current interferon treatment
- Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, has a negative imaging studies within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry.
- Patients with evidence or history of bleeding diathesis.
- Patients with seizure disorder requiring medication
- History of organ allograft
- Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
- Pregnant or breast-feeding patients.
Excluded concomitant medications:
- Concurrent anti-cancer chemotherapy, immunotherapy, or hormonal therapy except Bisphosphonates
- Radiotherapy during study or within 3 weeks of start of study drug.
- Biological response modifiers, such as Granulocyte-Colony Stimulating Factor (G-CFS) or Granulocyte macrophage colony-stimulating factor (GM-CFS), within 3 weeks prior to study entry or during study
- Significant surgery within 4 weeks prior to start of study drug
- Autologous bone marrow transplant or stem cell rescue within 4 months of study
- Investigational drug therapy during or within 4 weeks prior to first drug administration and during the study
- St John's Wort
- Xiao Chai Hu Tang
- Prior and concomitant use of Bevacizumab, and all other drugs (investigational or licensed) that target Vascular Endothelial Growth Factor (VEGF)/VEGF-Receptors, Raf-kinase inhibitors (RKI), Methyl Ethyl Ketone (MEK) or Farnesyl transferase inhibitors
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Sorafenib (Nexavar, BAY43-9006)
Arm Description
400 mg (2 tablets of 200 mg) of sorafenib per oral (PO) twice daily (BID)
Outcomes
Primary Outcome Measures
Pharmacokinetics Measured as Area Under Curve (AUC[0-12h])
The AUC(0-12h) was the observed AUC, calculated using a combination of linear and log trapezoidal rules, from pre-dose to 12 hours post-dose. The normalized AUC (AUC norm) is AUC (0-12h) divided by (dose [mg]/weight [kg]).
Pharmacokinetics Measured as Concentration (Cmax at Tmax and Cmin at Tmin)
Cmax (maximum concentration) was measured at the time point at which the maximum concentration (Tmax) was observed. Cmin (minimum concentration) was measured at the time point at which the minimum concentration (Tmin) was observed.
Pharmacokinetics Measured as Concentration (Cmax Normalized at Tmax and Cmin Normalized at Tmin)
Cmax (maximum concentration) was measured at the time point at which the maximum concentration (Tmax) was observed. Cmin (minimum concentration) was measured at the time point at which the minimum concentration (Tmin) was observed. The normalized variables (Cmax norm and Cmin norm) are the variables (Cmax and Cmin, see Primary Outcome Measure 2) divided by [dose (mg)/weight (kg)].
Secondary Outcome Measures
Progression Free Survival (PFS)
Progression-free survival (PFS) was defined as the time from the date of receipt of first dose of study drug to disease progression, radiological or clinical, or death, whichever was earlier. Subjects still alive without tumor progression at the time of analysis were censored at their date of last tumor evaluation.
Overall Survival (OS)
Overall survival (OS) was measured from the date of first dose of study drug until the date of death due to any cause. Survival time for subjects still alive at the time of analysis was censored at the date of last contact.
Time to Progression (TTP)
Time to progression (TTP) was defined as the time from date of receipt of first dose of study drug to disease progression, radiological or clinical. Subjects without tumor progression at the time of analysis were censored at their last date of tumor evaluation.
Disease Control (DC)
The DC was defined as subjects who had a best response rating of complete response (CR), partial response (PR), or stable disease (SD) according to Response Evaluation Criteria in Solid Tumors (RECIST) that was maintained for at least 28 days from the first demonstration of that rating. CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target). PR: at least a 30% decrease in the sum of longest diameters (LD) of target lesions taking as reference the baseline sum LD. SD: steady state of disease; do not qualify for PR or progressive disease (PD).
Overall Best Response
The best overall response was defined as the number of subjects with a confirmed CR, PR, SD, or PD. Tumor response was evaluated using RECIST. PD: at least a 20% increase in the sum of LD of measured lesions taking as ref. the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Appearance of new lesions will also constitute PD. In exceptional circumstances, unequivocal progression of a non-measured lesion may be accepted as evidence of disease progression.
Overall Response Duration
Overall response duration was to be calculated for subjects who had a confirmed PR or CR, defined as the time from first assessment showing a PR or CR to progression or death.
Time to Objective Response
Time to objective response was defined as the time from the date of receipt of first dose of study drug to first assessment showing a confirmed PR or CR.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00586105
Brief Title
Phase III Study of Sorafenib in Patients With Renal Cell Carcinoma (RCC)
Official Title
A Multicenter Uncontrolled Study of Sorafenib in Patients With Unresectable and/or Metastatic Renal Cell Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
December 2005 (undefined)
Primary Completion Date
May 2008 (Actual)
Study Completion Date
May 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
A multicenter uncontrolled study of sorafenib in patients with unresectable and/or metastatic renal cell carcinoma (RCC) to assess the pharmacokinetic profile, safety and tolerability, and efficacy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Renal Cell
Keywords
Sorafenib, Nexavar, Metastatic RCC, Renal Cell Carcinoma, Unresectable RCC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
39 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sorafenib (Nexavar, BAY43-9006)
Arm Type
Experimental
Arm Description
400 mg (2 tablets of 200 mg) of sorafenib per oral (PO) twice daily (BID)
Intervention Type
Drug
Intervention Name(s)
Sorafenib (Nexavar, BAY43-9006)
Intervention Description
400 mg (2 tablets of 200 mg) of sorafenib per oral (PO) twice daily (BID)
Primary Outcome Measure Information:
Title
Pharmacokinetics Measured as Area Under Curve (AUC[0-12h])
Description
The AUC(0-12h) was the observed AUC, calculated using a combination of linear and log trapezoidal rules, from pre-dose to 12 hours post-dose. The normalized AUC (AUC norm) is AUC (0-12h) divided by (dose [mg]/weight [kg]).
Time Frame
12 hours after at least 21 days of uninterrupted dosing
Title
Pharmacokinetics Measured as Concentration (Cmax at Tmax and Cmin at Tmin)
Description
Cmax (maximum concentration) was measured at the time point at which the maximum concentration (Tmax) was observed. Cmin (minimum concentration) was measured at the time point at which the minimum concentration (Tmin) was observed.
Time Frame
12 hours after at least 21 days of uninterrupted dosing
Title
Pharmacokinetics Measured as Concentration (Cmax Normalized at Tmax and Cmin Normalized at Tmin)
Description
Cmax (maximum concentration) was measured at the time point at which the maximum concentration (Tmax) was observed. Cmin (minimum concentration) was measured at the time point at which the minimum concentration (Tmin) was observed. The normalized variables (Cmax norm and Cmin norm) are the variables (Cmax and Cmin, see Primary Outcome Measure 2) divided by [dose (mg)/weight (kg)].
Time Frame
12 hours after at least 21 days of uninterrupted dosing
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
Progression-free survival (PFS) was defined as the time from the date of receipt of first dose of study drug to disease progression, radiological or clinical, or death, whichever was earlier. Subjects still alive without tumor progression at the time of analysis were censored at their date of last tumor evaluation.
Time Frame
Number of days from date of first dose of study drug to date first observed disease progression or death (whichever was earlier) was documented up to 17.25 months
Title
Overall Survival (OS)
Description
Overall survival (OS) was measured from the date of first dose of study drug until the date of death due to any cause. Survival time for subjects still alive at the time of analysis was censored at the date of last contact.
Time Frame
Time from start of therapy to death up to 17.25 months
Title
Time to Progression (TTP)
Description
Time to progression (TTP) was defined as the time from date of receipt of first dose of study drug to disease progression, radiological or clinical. Subjects without tumor progression at the time of analysis were censored at their last date of tumor evaluation.
Time Frame
Time from start of study medication to clinical or radiological disease progression which ever occurs first up to 17.25 months
Title
Disease Control (DC)
Description
The DC was defined as subjects who had a best response rating of complete response (CR), partial response (PR), or stable disease (SD) according to Response Evaluation Criteria in Solid Tumors (RECIST) that was maintained for at least 28 days from the first demonstration of that rating. CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target). PR: at least a 30% decrease in the sum of longest diameters (LD) of target lesions taking as reference the baseline sum LD. SD: steady state of disease; do not qualify for PR or progressive disease (PD).
Time Frame
From start to end of study medication up to 17.25 months
Title
Overall Best Response
Description
The best overall response was defined as the number of subjects with a confirmed CR, PR, SD, or PD. Tumor response was evaluated using RECIST. PD: at least a 20% increase in the sum of LD of measured lesions taking as ref. the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Appearance of new lesions will also constitute PD. In exceptional circumstances, unequivocal progression of a non-measured lesion may be accepted as evidence of disease progression.
Time Frame
Best response observed from start to end of study medication up to 17.25 months
Title
Overall Response Duration
Description
Overall response duration was to be calculated for subjects who had a confirmed PR or CR, defined as the time from first assessment showing a PR or CR to progression or death.
Time Frame
From PR or CR to progression or death up to 17.25 months
Title
Time to Objective Response
Description
Time to objective response was defined as the time from the date of receipt of first dose of study drug to first assessment showing a confirmed PR or CR.
Time Frame
Time from start of study medication to first documented PR or CR up to 17.25 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients who have a life expectancy of at least 12 weeks
Patients, who suffer from unresectable and/or metastatic, measurable RCC histologically or cytologically documented. Patients with rare subtypes of RCC such as pure papillary cell tumor, mixed tumor containing predominantly sarcomatoid cells, Bellini carcinoma, medullary carcinoma, or chromophobe oncocytic tumors are excluded from study participation.
Patients who have received not more than one prior systemic therapy for advanced disease which was completed at least 30 days prior to the first dose of study medication.
Patients who have at least one uni-dimensional measurable lesion by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI) according to Response Evaluation Criteria in Solid Tumours (RECIST)
Patients with "Intermediate" or "low" risk per the Motzer score
Patients who have an Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1
Adequate bone marrow, liver and renal function at screening as assessed by the following:
Total bilirubin < 1.5 x the upper limit of normal.
Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer).
Amylase and lipase < 1.5 x the upper limit of normal.
Serum creatinine < 2.0 x the upper limit of normal.
Prothrombin Time (PT) or International Normalized Ratio (INR) and Partial Thromboplastin Time (PTT) < 1.5 x upper limit of normal
Exclusion Criteria:
Previous or concurrent cancer that is distinct in primary sit or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, adequately treated basal cell carcinoma, superficial bladder tumors [Ta (Noninvasive papillary carcinoma), Tis (Carcinoma in situ: "flat tumor") and T1 (Tumor invades subepithelial connective tissue)] or any cancer curatively treated > 3 years prior to study entry)
Patients who completed their prior systemic treatment regimen less than 30 days
Cardiac arrhythmias requiring anti-arrhythmic (excluding beta blockers or digoxin), symptomatic coronary artery disease or ischemia
Active clinically serious bacterial or fungal infections
Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C requiring current interferon treatment
Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, has a negative imaging studies within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry.
Patients with evidence or history of bleeding diathesis.
Patients with seizure disorder requiring medication
History of organ allograft
Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
Pregnant or breast-feeding patients.
Excluded concomitant medications:
Concurrent anti-cancer chemotherapy, immunotherapy, or hormonal therapy except Bisphosphonates
Radiotherapy during study or within 3 weeks of start of study drug.
Biological response modifiers, such as Granulocyte-Colony Stimulating Factor (G-CFS) or Granulocyte macrophage colony-stimulating factor (GM-CFS), within 3 weeks prior to study entry or during study
Significant surgery within 4 weeks prior to start of study drug
Autologous bone marrow transplant or stem cell rescue within 4 months of study
Investigational drug therapy during or within 4 weeks prior to first drug administration and during the study
St John's Wort
Xiao Chai Hu Tang
Prior and concomitant use of Bevacizumab, and all other drugs (investigational or licensed) that target Vascular Endothelial Growth Factor (VEGF)/VEGF-Receptors, Raf-kinase inhibitors (RKI), Methyl Ethyl Ketone (MEK) or Farnesyl transferase inhibitors
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210003
Country
China
City
Beijing
ZIP/Postal Code
100021
Country
China
City
Shanghai
ZIP/Postal Code
200032
Country
China
City
Shanghai
ZIP/Postal Code
200127
Country
China
City
Tainan
ZIP/Postal Code
70428
Country
Taiwan
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
City
Taipei
ZIP/Postal Code
112
Country
Taiwan
City
Taoyuan
ZIP/Postal Code
333
Country
Taiwan
12. IPD Sharing Statement
Learn more about this trial
Phase III Study of Sorafenib in Patients With Renal Cell Carcinoma (RCC)
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