Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (SUMIT) - SUMIT

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 randomisation in the present study
• -Patients cannot have previously been treated with a systemic anti-cancer therapy. Patients can have prior intra-hepatic or non-systemic therapy. -Having received any of the following within the specified timeframe:
• Any prior systemic anti-cancer therapy for the treatment of this current diagnosis, An investigational drug within 30 days of starting treatment or within five half-lives of the compound (whichever is the most appropriate is at the discretion of the Investigator), or have not recovered from side effects of an investigational drug
• Any non-systemic anti-cancer therapy which has not been cleared from the body by the time of starting study treatment
• Radiation therapy within 4 weeks prior to starting study treatment, or limited field of radiation for palliation within 7 days of the first dose of study treatment
• Major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) which would prevent administration of study treatment,
• Any prior investigational therapy comprising inhibitors of RAS, RAF or MEK at any time,
• Previous treatment with dacarbazine.
• Any unresolved toxicity >CTCAE grade 2 from previous anti-cancer therapy, excluding alopecia
• -History of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib or dacarbazine
• --Symptomatic brain metastases or spinal cord compression (patients must be treated and stable off steroids and anti-convulsants for at least 1 month prior to entry into the study)
• Cardiac conditions as follows:
• - Uncontrolled hypertension (BP ≥150/95 mmHg despite medical therapy)
• - Acute coronary syndrome within 6 months prior to starting treatment
• - Uncontrolled Angina - Canadian Cardiovascular Society grade II-IV despite medical therapy - Symptomatic heart failure (New York Heart Association [NYHA] Class II-IV,- Prior or current cardiomyopathy
• - Baseline LVEF <55% measured by echocardiography or MUGA. Appropriate correction to be used if a MUGA is performed
• - Severe valvular heart disease
• - Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest
• - QTcF >450 ms or other factors that increase the risk of QTc prolongation
• -Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses 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
• -History of another primary malignancy within 5 years prior to starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study
• -Ophthalmologic conditions:
• - Current or past history of central serous retinopathy
• - Current or past history of retinal vein occlusion
• - IOP >21 mmHg or uncontrolled glaucoma (irrespective of IOP)
• -Female patients who are breast-feeding a child
• and
• male or female 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.
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