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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Melanoma

Intervention / Treatment
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* Drug: AZD6244
* Drug: Dacarbazine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>AZD6244 in combination with dacarbazine | Drug: AZD6244<br>* oral capsules, 75mg twice daily<br>* Other names: selumetinib;Drug: Dacarbazine<br>* 1000 mg/m2 iv infusion over at least 60 min. on day 1 of each 21 cycle<br>* Other names: DTIC;|
| Placebo Comparator: 2<br>Placebo in combination with dacarbazine | Drug: Dacarbazine<br>* 1000 mg/m2 iv infusion over at least 60 min. on day 1 of each 21 cycle<br>* Other names: DTIC;Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From randomization until evidence of RECIST-defined objective disease progression or data cut off, for a minimum of 12 months since start of treatment | 
| 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 | From randomization until evidence of RECIST-defined objective disease progression or data cut off, for a minimum of 12 months since start of treatment | 
| Change in Target Lesion Tumour Size at Week 12 |  | randomization to week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BRAF mutation positive, advanced melanoma, Advanced cutaneous melanoma, Unknown primary melanoma