A Phase II, Multi-centre, Open-Label, Parallel Group, Randomised Study To Compare the Efficacy of AZD6244 vs Temozolomide in Patients with Unresectable AJCC Stage 3 or 4 Malignant Melanoma

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 182

Inclusion Criteria

1.Provision of informed consent
2.Female or male aged 18 years and over
3.Histological or cytological confirmation of unresectable AJCC stage 3 or 4 malignant melanoma
4.At least one measurable site of disease (using CT/MRI) as defined by RECIST
5.WHO performance status 0-2 (patients performance status 2 must have been stable with no deterioration over the previous 2 weeks)
6.Willing to provide a fresh, or archival tumour biopsy for determination of BRAF and NRAS mutational status
7.Evidence of post-menopausal status, or negative urinary pregnancy test for female pre-menopausal patients

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

1.Laboratory values as listed below:
-Absolute Neutrophil Count (ANC) <1500 per cubic mm
-Platelets <100,000 per cubic mm
-Haemoglobin (Hgb) =9.0 g/dL
-Serum bilirubin =1.5 times the upper limit of normal (ULN)
-Aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) =2.5 times ULN
-Serum creatinine =1.5 mg/dL
2.Calculated serum creatinine clearance =30 mL/min (using Cockcroft-Gault formula)
3.Prior cancer treatment as follows:
-Any systemic chemotherapy for AJCC stage 3 or 4 melanoma
-Prior radiotherapy within the 5 years before starting study treatment excluding palliative radiotherapy at focal sites. Radiotherapy to treat primary uveal melanoma is permitted
-Prior chemotherapy within the 5 years prior to starting study treatment
Prior treatment with immunomodulatory agent, vaccine therapy or gene therapy alone is acceptable (combination biochemotherapy is not permitted)
4.Have received an investigational drug within the 30 days prior to entry or who have not recovered from side effects of an investigational study drug
5.Recent major surgery within 4 weeks prior to informed consent
6.Brain metastases or spinal cord compression unless treated and stable (for at least 3 months) off steroids
7.Patients with a history of another primary malignancy within 5 years prior to starting study treatment except for adequately treated basal or squamous cell carcinoma or carcinoma of the cervix in situ
8.Any evidence of severe or uncontrolled systemic disease (eg, severe hepatic impairment, severe renal impairment, uncontrolled diabetes, acute uncontrolled infection) or current unstable or uncompensated respiratory or cardiac conditions or peripheral vascular disease including diabetic vasculopathy
9.Evidence of active infection or active bleeding diatheses
10.Documented cases of human immunodeficiency virus (HIV) or hepatitis B or C
11.Refractory nausea and vomiting, chronic gastrointestinal diseases (eg, inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
12.Mean QTc interval >450 ms
13.Presence of factors that may increase the risk of QT prolongation or arrhythmic events (eg, heart failure, hypokalaemia, family history, or long QT syndrome)
14.Receiving concomitant medication that may cause QT prolongation
15.Known hypersensitivity to AZD6244, Captisol®, or temozolomide
16.Female patients who are breast feeding, or patients of reproductive potential not employing an effective method of birth control
17.Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site)
18.Previous enrolment or randomisation of treatment in the present study
19. Patients diagnosed with uveal melanoma, following closure of recruitment to such patients. (Recruitment will be closed to patients with uveal melanoma when AstraZeneca is notified that 20 patients with this diagnosis have been randomised)

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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