Back to resultsComparison of AZD6244 in Combination With Dacarbazine Versus (vs) Dacarbazine Alone in BRAF Mutation Positive Melanoma Patients
Primary Purpose
Melanoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AZD6244
Dacarbazine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Melanoma focused on measuring BRAF mutation positive, advanced melanoma, Advanced cutaneous melanoma, Unknown primary melanoma
Eligibility Criteria
Inclusion Criteria:
- Histological or cytological confirmation of advanced (inoperable stage III and stage IV) cutaneous or unknown primary melanoma
- Tumor sample confirmed as BRAF mutation positive
Exclusion Criteria:
- Diagnosis of uveal or mucosal melanoma
- Any prior Investigational therapy comprising inhibitors of Ras, Raf or MEK
- Having received an investigational drug within 30 days of starting treatment, or have not recovered from side effects of an investigational drug
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
1
2
Arm Description
AZD6244 in combination with dacarbazine
Placebo in combination with dacarbazine
Outcomes
Primary Outcome Measures
Overall Survival
Following progression survival data was collected until documentation of death, withdrawal of consent, loss to follow-up or the final data cut-off, whichever occurred first.
Secondary Outcome Measures
Progression Free Survival
PFS is the time from randomisation until the date of objective disease progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) or death (by any cause in the absence of progression). Progression is defined using RECIST (v1.1), as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm.
Objective Response Rate
ORR rate is defined as the number (%) of subjects with at least one visit response of Complete Response (CR) or Partial Response (PR) , as defined by Response Evaluation Criteria in Solid Tumours (RECIST v1.1) for target lesions and assessed by CT or MRI. CR, Disappearance of all target lesions; PR, ≥30% decrease in the sum of the longest diameter of target lesions. Data obtained up until progression, or last evaluable assessment in the absence of progression, was included in the assessment of ORR
Change in Target Lesion Tumour Size at Week 12
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00936221
Brief Title
Comparison of AZD6244 in Combination With Dacarbazine Versus (vs) Dacarbazine Alone in BRAF Mutation Positive Melanoma Patients
Official Title
A Phase II, Double-blind, Randomised Study to Assess the Efficacy of AZD6244 in Combination With Dacarbazine Compared With Dacarbazine Alone in First Line Patients With BRAF Mutation Positive Advanced Cutaneous or Unknown Primary Melanoma
Study Type
Interventional
2. Study Status
Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
November 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
5. Study Description
Brief Summary
To assess the efficacy in terms of overall survival of AZD6244 in combination with dacarbazine, compared with dacarbazine alone, in first line patients with BRAF mutation positive advanced cutaneous or unknown primary melanoma
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
BRAF mutation positive, advanced melanoma, Advanced cutaneous melanoma, Unknown primary melanoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
385 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
AZD6244 in combination with dacarbazine
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Placebo in combination with dacarbazine
Intervention Type
Drug
Intervention Name(s)
AZD6244
Other Intervention Name(s)
selumetinib
Intervention Description
oral capsules, 75mg twice daily
Intervention Type
Drug
Intervention Name(s)
Dacarbazine
Other Intervention Name(s)
DTIC
Intervention Description
1000 mg/m2 iv infusion over at least 60 min. on day 1 of each 21 cycle
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Overall Survival
Description
Following progression survival data was collected until documentation of death, withdrawal of consent, loss to follow-up or the final data cut-off, whichever occurred first.
Time Frame
From date of randomization until death, withdrawal of consent or the end of the study. The end of the study was defined as the date all AZD6244 patients had been followed for a minimum of 12 months, or the date of final analysis, whichever was later
Secondary Outcome Measure Information:
Title
Progression Free Survival
Description
PFS is the time from randomisation until the date of objective disease progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) or death (by any cause in the absence of progression). Progression is defined using RECIST (v1.1), as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm.
Time Frame
From randomization until evidence of RECIST-defined objective disease progression or data cut off, for a minimum of 12 months since start of treatment
Title
Objective Response Rate
Description
ORR rate is defined as the number (%) of subjects with at least one visit response of Complete Response (CR) or Partial Response (PR) , as defined by Response Evaluation Criteria in Solid Tumours (RECIST v1.1) for target lesions and assessed by CT or MRI. CR, Disappearance of all target lesions; PR, ≥30% decrease in the sum of the longest diameter of target lesions. Data obtained up until progression, or last evaluable assessment in the absence of progression, was included in the assessment of ORR
Time Frame
From randomization until evidence of RECIST-defined objective disease progression or data cut off, for a minimum of 12 months since start of treatment
Title
Change in Target Lesion Tumour Size at Week 12
Time Frame
randomization to week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
130 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histological or cytological confirmation of advanced (inoperable stage III and stage IV) cutaneous or unknown primary melanoma
Tumor sample confirmed as BRAF mutation positive
Exclusion Criteria:
Diagnosis of uveal or mucosal melanoma
Any prior Investigational therapy comprising inhibitors of Ras, Raf or MEK
Having received an investigational drug within 30 days of starting treatment, or have not recovered from side effects of an investigational drug
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Middleton, Dr
Organizational Affiliation
Churchil Hospital, Oxford, UK
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Caroline Robert, Dr
Organizational Affiliation
Institute Gustave Roussy, France
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ian Smith, Dr
Organizational Affiliation
AstraZeneca, Alderley Park, UK
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Aurora
State/Province
Colorado
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
Research Site
City
Belo Horizonte
Country
Brazil
Facility Name
Research Site
City
Ijuí
Country
Brazil
Facility Name
Research Site
City
Porto Alegre
Country
Brazil
Facility Name
Research Site
City
Sao Paulo
Country
Brazil
Facility Name
Research Site
City
Brno
Country
Czech Republic
Facility Name
Research Site
City
Novy Jicin
Country
Czech Republic
Facility Name
Research Site
City
Praha 2
Country
Czech Republic
Facility Name
Research Site
City
Lille Cedex
Country
France
Facility Name
Research Site
City
Marseille
Country
France
Facility Name
Research Site
City
Villejuif Cedex
Country
France
Facility Name
Research Site
City
Berlin
Country
Germany
Facility Name
Research Site
City
Essen
Country
Germany
Facility Name
Research Site
City
Hannover
Country
Germany
Facility Name
Research Site
City
Kiel
Country
Germany
Facility Name
Research Site
City
Tübingen
Country
Germany
Facility Name
Research Site
City
Budapest
Country
Hungary
Facility Name
Research Site
City
Györ
Country
Hungary
Facility Name
Research Site
City
Székesfehérvár
Country
Hungary
Facility Name
Research Site
City
Amsterdam
Country
Netherlands
Facility Name
Research Site
City
Nijmegen
Country
Netherlands
Facility Name
Research Site
City
Oslo
Country
Norway
Facility Name
Research Site
City
Barcelona
Country
Spain
Facility Name
Research Site
City
Houston
Country
Spain
Facility Name
Research Site
City
Málaga
Country
Spain
Facility Name
Research Site
City
Palma de Mallorca
Country
Spain
Facility Name
Research Site
City
Göteborg
Country
Sweden
Facility Name
Research Site
City
Malmö
Country
Sweden
Facility Name
Research Site
City
Stockholm
Country
Sweden
Facility Name
Research Site
City
Zürich
Country
Switzerland
Facility Name
Research Site
City
Cambridge
Country
United Kingdom
Facility Name
Research Site
City
Chelmsford
Country
United Kingdom
Facility Name
Research Site
City
London
Country
United Kingdom
Facility Name
Research Site
City
Manchester
Country
United Kingdom
Facility Name
Research Site
City
Newcastle upon Tyne
Country
United Kingdom
Facility Name
Research Site
City
Oxford
Country
United Kingdom
Facility Name
Research Site
City
Sutton
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
23735514
Citation
Robert C, Dummer R, Gutzmer R, Lorigan P, Kim KB, Nyakas M, Arance A, Liszkay G, Schadendorf D, Cantarini M, Spencer S, Middleton MR. Selumetinib plus dacarbazine versus placebo plus dacarbazine as first-line treatment for BRAF-mutant metastatic melanoma: a phase 2 double-blind randomised study. Lancet Oncol. 2013 Jul;14(8):733-40. doi: 10.1016/S1470-2045(13)70237-7. Epub 2013 Jun 2.
Results Reference
derived
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=195&filename=CSP-D1532C00006.pdf
Description
Related Info
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=195&filename=D1532C00006.pdf
Description
D1532C00006.pdf
Learn more about this trial
Comparison of AZD6244 in Combination With Dacarbazine Versus (vs) Dacarbazine Alone in BRAF Mutation Positive Melanoma Patients
We'll reach out to this number within 24 hrs