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

July 8, 2009
February 11, 2016
July 2009
November 2011   (final data collection date for primary outcome measure)
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.
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 [ Time Frame: Overall survival calculated as the interval from date of randomisation to date of patient death (any cause). Patients who have not died at final analysis, or who withdraw consent, will be censored at last date they were known to be alive. ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00936221 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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-Alive and Progression Free at 6 months (APF6)- Pr [ Time Frame: APF6, PFS, ORR, DoR, and change in tumour size at 12 weeks will be assessed using RECIST measurements. RECIST assessments to be carried out at baseline, week 12 and every 12 weeks thereafter relative to randomisation ] [ Designated as safety issue: No ]
  • To assess the safety and tolerability profile of AZD6244 in combination with dacarbazine [ Time Frame: At every visit (ie weekly for the first 6 weeks and then every 3 weeks) ] [ Designated as safety issue: Yes ]
  • To investigate the pharmacokinetics of AZD6244 [ Time Frame: At Day 1 and Day 22 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Comparison of AZD6244 in Combination With Dacarbazine Versus (vs) Dacarbazine Alone in BRAF Mutation Positive Melanoma Patients
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
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
Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Melanoma
  • 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
  • Drug: Placebo
    Placebo
  • Active Comparator: 1
    AZD6244 in combination with dacarbazine
    Interventions:
    • Drug: AZD6244
    • Drug: Dacarbazine
  • Placebo Comparator: 2
    Placebo in combination with dacarbazine
    Interventions:
    • Drug: Dacarbazine
    • Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
385
November 2014
November 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 130 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Brazil,   Czech Republic,   France,   Germany,   Hungary,   Netherlands,   Norway,   Spain,   Sweden,   Switzerland,   United Kingdom
Australia
 
NCT00936221
D1532C00006
Not Provided
Not Provided
Not Provided
AstraZeneca
AstraZeneca
Not Provided
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
AstraZeneca
February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP