A Phase II, Double-Blind, Randomised Study to Assess the Efficacy of AZD6244 (Hyd-Sulfate) in Combination with Dacarbazine Compared with Dacarbazine Alone in First Line Patients with BRAF Mutation Positive Advanced Cutaneous or Unknown Primary Melanoma

Phase 1

Conditions: BRAF mutation positive advanced cutaneous and unknown primary melanoma
MedDRA version: 9.1Level: LLTClassification code 10025654Term: Malignant melanoma of sites other than skin
MedDRA version: 9.1Level: LLTClassification code 10025670Term: Malignant melanoma stage III
MedDRA version: 9.1Level: LLTClassification code 10025671Term: Malignant melanoma stage IV
MedDRA version: 9.1Level: LLTClassification code 10027152Term: Melanoma of skin (malignant)
MedDRA version: 9.1Level: LLTClassification code 10027480Term: Metastatic malignant melanoma

Registration Number: EUCTR2008-006344-19-FR

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 91

Inclusion Criteria

Provision of signed, written and dated informed consent prior to any study specific procedures
Male or female, aged 18 years or older
Histological or cytological confirmation of advanced cutaneous or unknown primary melanoma
WHO performance status 0 1
At least one lesion, not previously irradiated, that can be accurately measured at baseline as =10 mm in the longest diameter (LD; except lymph nodes which must have a short axis =15 mm) with CT or MRI, and which is suitable for accurate repeated measurements.
Tumour sample confirmed as BRAF mutation positive (Note: sample must be available upon enrolment to ship to the AstraZeneca appointed central laboratory, or mutation status confirmed locally at an AstraZeneca agreed local laboratory using agreed methodology.
Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients. Post menopausal status is defined as:
-natural menopause with menses >1 year ago
-radiation induced oophorectomy with last menses >1 year ago
-chemotherapy-induced menopause with 1 year interval since last menses
-serum FSH and LH and plasma oestradiol levels in the postmenopausal range for the institution
-bilateral oophorectomy or hysterectomy
Serum creatinine clearance >50 ml/min, by either Cockcroft-Gault formula or 24 hour urine collection analysis
Patients should be able to swallow AZD6244/placebo capsules.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
Previous randomization of treatment in the present study
Having received an investigational drug within the 30 days prior to entry, or have not recovered from side effects of an investigational drug
Diagnosis of uveal or mucosal melanoma
Any prior Investigational therapy comprising inhibitors of Ras, Raf or MEK
Any prior cytotoxic chemotherapy or biochemotherapy for advanced melanoma
patients who previously received adjuvant biochemotherapy will be eligible, unless their treatment included temozolomide or dacarbazine
Any other investigational non-chemotherapeutic therapy for advanced melanoma, with the exception of prior monotherapy with interleukin-2, cytokines (eg, a interferon or GM-CSF) or vaccine, which are permitted- use of anti-CTLA4 monoclonal antibodies will be allowed in adjuvant settings
Any non-systemic therapy (except focal palliative radiotherapy) for advanced melanoma within 30 days of starting study treatment
Any unresolved toxicity above CTCAE grade 2 from previous anti-cancer therapy, apart from alopecia
Brain metastases or spinal cord compression unless treated and stable off treatment (eg, steroids) for at least 3 months
Laboratory values as listed below (from laboratory results at Visit 1):
-ANC <1.5x109/L (1,500 per mm3)
-Platelets <100x109/L (100,000 per mm3)
-Haemoglobin =9.0 g/dL
-Serum bilirubin >1.5xULN
-AST or ALT >2.5xULN
LDH =2xULN (from the Visit 1 laboratory result)
Cardiac conditions as follows:
-Uncontrolled hypertension (BP=150/95 despite optimal therapy)
-Heart failure NYHA Class II or above
-Prior or current cardiomyopathy
-Baseline LVEF =50%
-Atrial fibrillation with heart rate >100 bpm
-Unstable ischaemic heart disease (myocardial infarction within 6 months prior to starting treatment, or angina requiring use of nitrates more than once weekly)
Major surgery within 4 weeks prior to starting study treatment
Hypersensitivity to AZD6244, or dacarbazine or any excipient of these agents
Patients with a history of another primary malignancy within 5 years prior to starting study treatment, except adequately treated basal or squamous cell carcinoma of the skin, or carcinoma of the cervix in situ and the disease under study
Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diathesis or renal transplant, including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
Refractory nausea and vomiting, chronic gastrointestinal diseases (eg, inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
Female patients who are breast-feeding or patients of reproductive potential who are not employing an effective method of birth control
Clinical judgement by the investigator that the patient should not participate in the study.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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