Comparison of AZD6244 in Combination With Dacarbazine Versus (vs) Dacarbazine Alone in BRAF Mutation Positive Melanoma Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00936221
First received: July 8, 2009
Last updated: February 11, 2016
Last verified: February 2016
  Purpose
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

Condition Intervention Phase
Melanoma
Drug: AZD6244
Drug: Dacarbazine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Overall Survival [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: randomization to week 12 ] [ Designated as safety issue: No ]

Enrollment: 385
Study Start Date: July 2009
Study Completion Date: November 2014
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
AZD6244 in combination with dacarbazine
Drug: AZD6244
oral capsules, 75mg twice daily
Other Name: selumetinib
Drug: Dacarbazine
1000 mg/m2 iv infusion over at least 60 min. on day 1 of each 21 cycle
Other Name: DTIC
Placebo Comparator: 2
Placebo in combination with dacarbazine
Drug: Dacarbazine
1000 mg/m2 iv infusion over at least 60 min. on day 1 of each 21 cycle
Other Name: DTIC
Drug: Placebo
Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 130 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00936221

  Show 38 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Mark Middleton, Dr Churchil Hospital, Oxford, UK
Principal Investigator: Caroline Robert, Dr Institute Gustave Roussy, France
Study Director: Ian Smith, Dr AstraZeneca, Alderley Park, UK
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00936221     History of Changes
Other Study ID Numbers: D1532C00006 
Study First Received: July 8, 2009
Results First Received: November 4, 2015
Last Updated: February 11, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
BRAF mutation positive
advanced melanoma
Advanced cutaneous melanoma
Unknown primary melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on August 24, 2016