Back to resultsA Phase II, Multi-Center, Open-Label, Uncontrolled Study to Evaluate the Efficacy and Safety of Sorafenib Given Daily in Combination With Repeated 21-Day Cycles of Dacarbazine (DTIC) Chemotherapy in Subjects With Advanced Metastatic Melanoma
Primary Purpose
Melanoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Sorafenib (Nexavar, BAY43-9006) + Dacarbazine (DTIC)
Sponsored by
About this trial
This is an interventional treatment trial for Melanoma
Eligibility Criteria
Inclusion Criteria:
- Subjects with advanced, metastatic, histologically confirmed melanoma, for whom treatment with dacarbazine is considered medically acceptable
- Age >= 18 years
- Subject has measurable and evaluable disease defined as at least one metastatic lesion that can be accurately and serially measured by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan as per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Cutaneous lesions measuring at least 20mm in longest diameter can be considered measurable (and therefore target lesions) via color photography including a ruler
- Subject has biopsiable disease at baseline and is willing to provide biopsy samples, or does not have biopsiable disease at baseline
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Exclusion Criteria:
- Primary ocular or mucosal melanoma (cutaneous vulval melanoma is permitted)
- Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry
- (Active coronary artery disease or ischemia (myocardial infarction more than 6 months prior to study entry is allowed)
- Uncontrolled hypertension (> grade 2 National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0)
- Active, clinically serious infections (> grade 2 NCI-CTCAE version 3.0)
- Subjects with seizure disorder requiring medication are excluded
- History of or suspected Human Immunodeficiency Virus (HIV) infection, or chronic hepatitis B or C
- Symptomatic metastatic brain or meningeal tumors unless the subject is > 6 months from definitive therapy, has a negative imaging study within 4 weeks prior to study entry and is clinically stable with respect to the tumor at the time of study entry. Also the subject must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies)
- Pregnant or breast-feeding subjects
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Sorafenib + Dacarbazine
Arm Description
Dacarbazine 1000 mg/m^2 on day one of repeated 21 day cycles, in combination with daily continuous oral sorafenib (Nexavar, BAY 43-9006), 400 mg twice a day (bid)
Outcomes
Primary Outcome Measures
Overall Best Response
Best Overall Response (BOR): Best tumor response achieved during or within 30 days after active therapy confirmed according to the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR): The disappearance of all target and non-target lesions. Partial response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. SD was defined as steady state of disease, PD was defined as an increase of at least 20% increase in the sum of the LD of target lesions or appearance of new lesions.
Secondary Outcome Measures
Progression-free Survival
Progression-free Survival (PFS) was the time from the first dose of combination therapy to disease progression (radiological or clinical, whichever is earlier) or death (if death occurs before progression is documented). PFS for subjects without tumor progression or death at the time of analysis were censored at the date of last tumor evaluation.
Percentage of Subjects With Progression-free Survival at Specific Time-points
Progression-free Survival (PFS) was the time from the first dose of combination therapy to disease progression (radiological or clinical, whichever is earlier) or death (if death occurs before progression is documented). PFS for subjects without tumor progression or death at the time of analysis were censored at the date of last tumor evaluation.
Overall Survival
Overall Survival was the number of days from the date that combination treatment started until the date of death.
Duration of Response
Duration of Response was assessed in subjects who showed a Partial Response (PR) or Complete Response (CR). It was defined as the time from the first documented objective response to Progressive Disease (PD), or death if before documented progression. Duration of response for subjects who have not progressed or died at the time of analysis was censored at the date of last tumor assessment.
Duration of Complete Response
Duration of complete response was the number of days from the date that a complete response was first documented to the date that recurrent or progressive disease was first objectively documented (if patient progressed then censored=no) or to last observation (if patient did not progress then censored=yes).
Duration of Partial Response
Duration of partial response was the number of days from the date that a partial response was first documented to the date that recurrent or progressive disease was first objectively documented (if patient progressed then censored=no) or to last observation (if patient did not progress then censored=yes).
Disease Control (DC)
DC was defined as the total number of subjects whose best response was not progressive disease (PD) (total number of CRs + total number of PRs + total number of Stable Diseases (SD)). The DC at specific time points could also be calculated as the total number of subjects whose response was not PD at that time point.
Duration of Stable Disease
Duration of Stable Disease (DSD), defined as the time from the first documented objective evidence of Stable Disease (SD) to disease progression (DP) or death if death occurred before DP, was assessed in subjects who showed SD as best response. DSD for subjects who had not progressed or died was censored at the date of last tumor assessment.
Time to Response
Time to Response in subjects who achieved an objective response (PR or CR with confirmation) was measured from the date of starting study combination treatment until the earliest date that the response was first documented.
Time to Progression
Time to Progression was the number of days from the start of therapy to progression (if patient progressed then censored=no) or to the last observation at which the patient was known to have not progressed, that is, the last observation with a best response of CR, PR, or SD.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00492297
Brief Title
A Phase II, Multi-Center, Open-Label, Uncontrolled Study to Evaluate the Efficacy and Safety of Sorafenib Given Daily in Combination With Repeated 21-Day Cycles of Dacarbazine (DTIC) Chemotherapy in Subjects With Advanced Metastatic Melanoma
Official Title
A Phase II, Multi-center, Open-label, Uncontrolled Study to Evaluate the Efficacy and Safety of BAY 43-9006 Given Daily in Combination With Repeated 21-Day Cycles of Dacarbazine (DTIC) Chemotherapy in Subjects With Advanced Metastatic Melanoma.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
April 2005 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
July 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
The purpose of this study is to see whether a new type of anti-cancer drug, known as BAY 43-9006, can be given safely and with good effect in combination with dacarbazine (DTIC). DTIC is the current standard chemotherapy drug given for melanoma that has spread through the body. Although this drug can be effective on its own and is generally well tolerated, not all patients will benefit, so there is a need to test new drugs and drug combinations for treating melanoma.
Detailed Description
Issues on "Safety" outcomes are addressed in the Adverse Event section.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
83 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sorafenib + Dacarbazine
Arm Type
Experimental
Arm Description
Dacarbazine 1000 mg/m^2 on day one of repeated 21 day cycles, in combination with daily continuous oral sorafenib (Nexavar, BAY 43-9006), 400 mg twice a day (bid)
Intervention Type
Drug
Intervention Name(s)
Sorafenib (Nexavar, BAY43-9006) + Dacarbazine (DTIC)
Intervention Description
Dacarbazine 1000 mg/m^2 on day one of repeated 21 day cycles, in combination with daily continuous oral sorafenib (Nexavar, BAY 43-9006), 400 mg twice a day (bid)
Primary Outcome Measure Information:
Title
Overall Best Response
Description
Best Overall Response (BOR): Best tumor response achieved during or within 30 days after active therapy confirmed according to the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR): The disappearance of all target and non-target lesions. Partial response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. SD was defined as steady state of disease, PD was defined as an increase of at least 20% increase in the sum of the LD of target lesions or appearance of new lesions.
Time Frame
during or within 30 days after active therapy
Secondary Outcome Measure Information:
Title
Progression-free Survival
Description
Progression-free Survival (PFS) was the time from the first dose of combination therapy to disease progression (radiological or clinical, whichever is earlier) or death (if death occurs before progression is documented). PFS for subjects without tumor progression or death at the time of analysis were censored at the date of last tumor evaluation.
Time Frame
from start of treatment until progression or death before progression (median 259 days)
Title
Percentage of Subjects With Progression-free Survival at Specific Time-points
Description
Progression-free Survival (PFS) was the time from the first dose of combination therapy to disease progression (radiological or clinical, whichever is earlier) or death (if death occurs before progression is documented). PFS for subjects without tumor progression or death at the time of analysis were censored at the date of last tumor evaluation.
Time Frame
from start of treatment until progression or death before progression after 3, 6 and 12 months
Title
Overall Survival
Description
Overall Survival was the number of days from the date that combination treatment started until the date of death.
Time Frame
from start of treatment until death (median 259 days)
Title
Duration of Response
Description
Duration of Response was assessed in subjects who showed a Partial Response (PR) or Complete Response (CR). It was defined as the time from the first documented objective response to Progressive Disease (PD), or death if before documented progression. Duration of response for subjects who have not progressed or died at the time of analysis was censored at the date of last tumor assessment.
Time Frame
from confirmed Complete Response (CR) or Partial Response (PR) until Progressive Disease (PD) (median 259 days)
Title
Duration of Complete Response
Description
Duration of complete response was the number of days from the date that a complete response was first documented to the date that recurrent or progressive disease was first objectively documented (if patient progressed then censored=no) or to last observation (if patient did not progress then censored=yes).
Time Frame
from confirmed CR until PD (median 259 days)
Title
Duration of Partial Response
Description
Duration of partial response was the number of days from the date that a partial response was first documented to the date that recurrent or progressive disease was first objectively documented (if patient progressed then censored=no) or to last observation (if patient did not progress then censored=yes).
Time Frame
from confirmed PR until PD (median 259 days)
Title
Disease Control (DC)
Description
DC was defined as the total number of subjects whose best response was not progressive disease (PD) (total number of CRs + total number of PRs + total number of Stable Diseases (SD)). The DC at specific time points could also be calculated as the total number of subjects whose response was not PD at that time point.
Time Frame
after start of treatment, at 6 months and 12 months
Title
Duration of Stable Disease
Description
Duration of Stable Disease (DSD), defined as the time from the first documented objective evidence of Stable Disease (SD) to disease progression (DP) or death if death occurred before DP, was assessed in subjects who showed SD as best response. DSD for subjects who had not progressed or died was censored at the date of last tumor assessment.
Time Frame
from start of therapy to PD, only in non-responders (median 259 days)
Title
Time to Response
Description
Time to Response in subjects who achieved an objective response (PR or CR with confirmation) was measured from the date of starting study combination treatment until the earliest date that the response was first documented.
Time Frame
start of therapy to confirmed CR or PR (median 259 days)
Title
Time to Progression
Description
Time to Progression was the number of days from the start of therapy to progression (if patient progressed then censored=no) or to the last observation at which the patient was known to have not progressed, that is, the last observation with a best response of CR, PR, or SD.
Time Frame
From start of treatment until progression (median 259 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects with advanced, metastatic, histologically confirmed melanoma, for whom treatment with dacarbazine is considered medically acceptable
Age >= 18 years
Subject has measurable and evaluable disease defined as at least one metastatic lesion that can be accurately and serially measured by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan as per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Cutaneous lesions measuring at least 20mm in longest diameter can be considered measurable (and therefore target lesions) via color photography including a ruler
Subject has biopsiable disease at baseline and is willing to provide biopsy samples, or does not have biopsiable disease at baseline
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Exclusion Criteria:
Primary ocular or mucosal melanoma (cutaneous vulval melanoma is permitted)
Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry
(Active coronary artery disease or ischemia (myocardial infarction more than 6 months prior to study entry is allowed)
Uncontrolled hypertension (> grade 2 National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0)
Active, clinically serious infections (> grade 2 NCI-CTCAE version 3.0)
Subjects with seizure disorder requiring medication are excluded
History of or suspected Human Immunodeficiency Virus (HIV) infection, or chronic hepatitis B or C
Symptomatic metastatic brain or meningeal tumors unless the subject is > 6 months from definitive therapy, has a negative imaging study within 4 weeks prior to study entry and is clinically stable with respect to the tumor at the time of study entry. Also the subject must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies)
Pregnant or breast-feeding subjects
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
Lyon Cedex
ZIP/Postal Code
39373
Country
France
City
Toulouse
ZIP/Postal Code
31052
Country
France
City
Villejuif
ZIP/Postal Code
94805
Country
France
City
Cambridge
State/Province
Cambridgeshire
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
City
Southampton
State/Province
Hampshire
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
City
Northwood
State/Province
Middlesex
ZIP/Postal Code
HA6 2RN
Country
United Kingdom
City
Sutton
State/Province
Surrey
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
City
London
ZIP/Postal Code
SE1 7EH
Country
United Kingdom
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
21750549
Citation
Eisen T, Marais R, Affolter A, Lorigan P, Robert C, Corrie P, Ottensmeier C, Chevreau C, Chao D, Nathan PD, Jouary T, Harries M, Negrier S, Montegriffo E, Ahmad T, Gibbens I, James MG, Strauss UP, Prendergast S, Gore ME. Sorafenib and dacarbazine as first-line therapy for advanced melanoma: phase I and open-label phase II studies. Br J Cancer. 2011 Jul 26;105(3):353-9. doi: 10.1038/bjc.2011.257. Epub 2011 Jul 12.
Results Reference
result
Links:
URL
http://www.clinicaltrialsregister.eu
Description
Click here and search for information of Bayer products for Europe
Learn more about this trial
A Phase II, Multi-Center, Open-Label, Uncontrolled Study to Evaluate the Efficacy and Safety of Sorafenib Given Daily in Combination With Repeated 21-Day Cycles of Dacarbazine (DTIC) Chemotherapy in Subjects With Advanced Metastatic Melanoma
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