Back to resultsSorafenib Dose Escalation in Renal Cell Carcinoma
Primary Purpose
Carcinoma, Renal Cell
Status
Completed
Phase
Phase 2
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 Kidney cancer,, Sorafenib,, Dose escalation,, No previous treatment
Eligibility Criteria
Inclusion Criteria:
- Age > 18 years.
- Metastatic clear cell RCC (renal cell carcinoma)
- Subjects with at least one uni-dimensional measurable lesion.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Memorial Sloan Kettering Cancer Center (MSKCC) good or intermediate category
- Life expectancy of at least 12 weeks.
- Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to treatment
- Signed informed consent must be obtained prior to any study specific procedures.
- Subjects must have received no prior systemic anticancer therapy for the treatment of their renal cell carcinoma
- Prior total nephrectomy
Exclusion Criteria:
- History of cardiac disease
- History of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
- Active clinically serious infections (> grade 2 National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 3.0)
- Symptomatic metastatic brain or meningeal tumors unless the subject is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry.
- Subjects with evidence or history of bleeding diathesis
- Deep vein thrombosis and/or pulmonary embolus within 12 months of the start of treatment.
- Delayed healing of wounds, ulcers or bone fractures
- Subjects with pre-existing thyroid abnormality whose thyroid function cannot be maintained within the normal range by medication
- Subjects undergoing renal dialysis
- Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and three months after the completion of trial.
- Prior adjuvant sorafenib is excluded.
- Radiotherapy during study or within 3 weeks of start of study drug
- Major surgery within 4 weeks of start of study
- Investigational drug therapy outside of this trial during or within 4 weeks of study entry
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Sorafenib (Nexavar, BAY43-9006)
Arm Description
Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle, 600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed.
Outcomes
Primary Outcome Measures
Best Response - mITT (Modified Intent-to-treat) Population
Best Response (Response Rate) of a subject was defined as the proportion of patients with confirmed Complete Response (CR) or Partial Response (PR) as their best response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed CR was defined as disappearance of tumor and PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes.
Tumor Response - ITT (Intent to Treat) Population
Tumor Response of a subject was defined as the best tumor response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed Complete Response (CR) was defined as disappearance of tumor, Partial Response (PR) was defined as a decrease of at least 30% in the sum of target lesions, Stable Disease (SD) was defined as steady state of disease, and Progressive Disease (PD) was defined as at least a 20% increase in the sum of measured lesions or appearance of new lesions.
Secondary Outcome Measures
Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 10 Hours Postdose (AUC(0-10),ss)
AUC(0-10),ss was defined as an area under the plasma concentration versus time curve from time zero to 10 hours post-dose. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.
Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 12 Hours Postdose (AUC(0-12),ss)
AUC(0-12),ss was defined as an area under the plasma concentration versus time curve from time zero to 12 hours post-dose. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.
Pharmacokinetics (PK) Analysis - Maximum Observed Concentration in Plasma (Cmax)
Cmax was defined as a maximum plasma concentration at steady-state. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.
Pharmacokinetics (PK) Analysis - Time to Maximum Concentration (Tmax)
Tmax was defined as a time to maximum concentration at steady-state. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.
Progression-free Survival (PFS)
Progression-free survival (PFS) was defined as the time from start of study medication to the first documented disease progression per RECIST (by independent radiological assessment) or clinical progression as per investigator assessment or death due to any cause whichever occurred first. For patients who had not recurred or died at the time of analysis, PFS was censored at their last date of evaluable scan.
Time to Progression (TTP)
Time to progression (TTP) was defined as the time from start of study medication to the first documented disease progression per RECIST (by independent radiological assessment) or clinical progression as per investigator assessment whichever occurred first. For patients who had not progressed at the time of analysis or died before progression, TTP was censored at their last date of evaluable scan.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00618982
Brief Title
Sorafenib Dose Escalation in Renal Cell Carcinoma
Official Title
A Phase II, Multi-centre, Open-label Study to Assess the Efficacy, Safety, Tolerability and Pharmacokinetics of Intrapatient Dose Escalation of Sorafenib as First Line Treatment for Metastatic Renal Cell Carcinoma.
Study Type
Interventional
2. Study Status
Record Verification Date
November 2015
Overall Recruitment Status
Completed
Study Start Date
February 2008 (undefined)
Primary Completion Date
April 2009 (Actual)
Study Completion Date
January 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Sorafenib is a new drug, which is approved under the brand name Nexavar for the treatment of advanced kidney cancer. It is also currently being tested in various other cancers. Sorafenib works by stopping the development of new cancer cells and new blood vessels. By stopping the growth of new blood vessels around a tumor, it is believed that sorafenib prevents the growth of kidney cancer tumors.
This is an "open-label" study which means that the patient, the doctor and Bayer Healthcare will know what tablets the patient is taking. All patients in this study will receive sorafenib tablets. Sorafenib is taken orally as a tablet (two tablets are taken twice a day). Treatment with sorafenib will continue until the patient's tumor grows larger or spreads further or if the patient has intolerable side effects. The dose of sorafenib that the patient will receive in the study will increase at certain points during the patient's treatment, as long as the patient is not experiencing side effects and the patient's tumor has not grown.
Detailed Description
Issues on Outcome Measure "Safety and tolerability" will be addressed in the Adverse Events section.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Renal Cell
Keywords
Kidney cancer,, Sorafenib,, Dose escalation,, No previous 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
83 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sorafenib (Nexavar, BAY43-9006)
Arm Type
Experimental
Arm Description
Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle, 600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed.
Intervention Type
Drug
Intervention Name(s)
Sorafenib (Nexavar, BAY43-9006)
Intervention Description
The initial dose of sorafenib will be 400 mg bid administered orally, on a continuous basis. A treatment cycle is considered to be 28 days. Intrapatient dose escalation will occur according to the following schedule, providing no grade 3 or 4 toxicities are observed (except for alopecia, nausea and vomiting); Day 1-28 400 mg bid, Day 29-56 600 mg bid, Day 57 onwards 800 mg bid. Subjects will continue on treatment until progression, unacceptable toxicity, subject withdraws consent or the decision is taken to stop the study following the analysis of response rates.
Primary Outcome Measure Information:
Title
Best Response - mITT (Modified Intent-to-treat) Population
Description
Best Response (Response Rate) of a subject was defined as the proportion of patients with confirmed Complete Response (CR) or Partial Response (PR) as their best response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed CR was defined as disappearance of tumor and PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes.
Time Frame
Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
Title
Tumor Response - ITT (Intent to Treat) Population
Description
Tumor Response of a subject was defined as the best tumor response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed Complete Response (CR) was defined as disappearance of tumor, Partial Response (PR) was defined as a decrease of at least 30% in the sum of target lesions, Stable Disease (SD) was defined as steady state of disease, and Progressive Disease (PD) was defined as at least a 20% increase in the sum of measured lesions or appearance of new lesions.
Time Frame
Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 10 Hours Postdose (AUC(0-10),ss)
Description
AUC(0-10),ss was defined as an area under the plasma concentration versus time curve from time zero to 10 hours post-dose. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.
Time Frame
Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8 and 10 hours post-dose.
Title
Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 12 Hours Postdose (AUC(0-12),ss)
Description
AUC(0-12),ss was defined as an area under the plasma concentration versus time curve from time zero to 12 hours post-dose. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.
Time Frame
Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8, 10 and 12 hours post-dose.
Title
Pharmacokinetics (PK) Analysis - Maximum Observed Concentration in Plasma (Cmax)
Description
Cmax was defined as a maximum plasma concentration at steady-state. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.
Time Frame
Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8, 10 and 12 hours post-dose.
Title
Pharmacokinetics (PK) Analysis - Time to Maximum Concentration (Tmax)
Description
Tmax was defined as a time to maximum concentration at steady-state. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.
Time Frame
Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8, 10 and 12 hours post-dose.
Title
Progression-free Survival (PFS)
Description
Progression-free survival (PFS) was defined as the time from start of study medication to the first documented disease progression per RECIST (by independent radiological assessment) or clinical progression as per investigator assessment or death due to any cause whichever occurred first. For patients who had not recurred or died at the time of analysis, PFS was censored at their last date of evaluable scan.
Time Frame
Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
Title
Time to Progression (TTP)
Description
Time to progression (TTP) was defined as the time from start of study medication to the first documented disease progression per RECIST (by independent radiological assessment) or clinical progression as per investigator assessment whichever occurred first. For patients who had not progressed at the time of analysis or died before progression, TTP was censored at their last date of evaluable scan.
Time Frame
Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
Other Pre-specified Outcome Measures:
Title
Tumor Response - mITT Population
Description
Tumor Response of a subject was defined as the best tumor response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed Complete Response (CR) was defined as disappearance of tumor, Partial Response (PR) was defined as a decrease of at least 30% in the sum of target lesions, Stable Disease (SD) was defined as steady state of disease, and Progressive Disease (PD) was defined as at least a 20% increase in the sum of measured lesions or appearance of new lesions.
Time Frame
Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
Title
Disease Control - mITT Population
Description
Disease Control (DC) of a subject was defined as the proportion of patients with confirmed Complete Response (CR), Partial Response (PR) or Stable Disease (SD) as their best response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed CR was defined as disappearance of tumor, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, and SD was defined as steady state of disease.
Time Frame
Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age > 18 years.
Metastatic clear cell RCC (renal cell carcinoma)
Subjects with at least one uni-dimensional measurable lesion.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Memorial Sloan Kettering Cancer Center (MSKCC) good or intermediate category
Life expectancy of at least 12 weeks.
Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to treatment
Signed informed consent must be obtained prior to any study specific procedures.
Subjects must have received no prior systemic anticancer therapy for the treatment of their renal cell carcinoma
Prior total nephrectomy
Exclusion Criteria:
History of cardiac disease
History of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
Active clinically serious infections (> grade 2 National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 3.0)
Symptomatic metastatic brain or meningeal tumors unless the subject is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry.
Subjects with evidence or history of bleeding diathesis
Deep vein thrombosis and/or pulmonary embolus within 12 months of the start of treatment.
Delayed healing of wounds, ulcers or bone fractures
Subjects with pre-existing thyroid abnormality whose thyroid function cannot be maintained within the normal range by medication
Subjects undergoing renal dialysis
Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and three months after the completion of trial.
Prior adjuvant sorafenib is excluded.
Radiotherapy during study or within 3 weeks of start of study drug
Major surgery within 4 weeks of start of study
Investigational drug therapy outside of this trial during or within 4 weeks of study entry
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
Bordeaux
ZIP/Postal Code
33000
Country
France
City
La Roche Sur Yon
ZIP/Postal Code
85925
Country
France
City
Marseille
ZIP/Postal Code
13385
Country
France
City
Nantes
ZIP/Postal Code
44805
Country
France
City
Paris Cedex 10
ZIP/Postal Code
75475
Country
France
City
Tours
ZIP/Postal Code
37044
Country
France
City
Tübingen
State/Province
Baden-Württemberg
ZIP/Postal Code
72076
Country
Germany
City
Marburg
State/Province
Hessen
ZIP/Postal Code
35043
Country
Germany
City
Hannover
State/Province
Niedersachsen
ZIP/Postal Code
30625
Country
Germany
City
Mainz
State/Province
Rheinland-Pfalz
ZIP/Postal Code
55131
Country
Germany
City
Jena
State/Province
Thüringen
ZIP/Postal Code
07740
Country
Germany
City
Aviano
State/Province
Pordenone
ZIP/Postal Code
33081
Country
Italy
City
Milano
ZIP/Postal Code
20133
Country
Italy
City
Pavia
ZIP/Postal Code
27100
Country
Italy
City
Olsztyn
ZIP/Postal Code
10-226
Country
Poland
City
Warszawa
ZIP/Postal Code
02-781
Country
Poland
City
Warszawa
ZIP/Postal Code
04-141
Country
Poland
City
Wroclaw
ZIP/Postal Code
50 - 556
Country
Poland
City
Greater Manchester
State/Province
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
City
Cardiff
State/Province
South Glamorgan
ZIP/Postal Code
CF14 7TB
Country
United Kingdom
City
Glasgow
ZIP/Postal Code
G12 0YN
Country
United Kingdom
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
12. IPD Sharing Statement
Links:
URL
http://www.clinicaltrialsregister.eu
Description
Click here and search for Bayer product information provided by EMA
Learn more about this trial
Sorafenib Dose Escalation in Renal Cell Carcinoma
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