Saracatinib in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed By Surgery

PRIMARY OBJECTIVES:

I. To determine whether the Src kinase inhibitor, AZD0530 (saracatinib), has single agent clinical activity in patients with advanced melanoma.

II. To determine whether this drug will increase progression-free survival of these patients from 3 months to 4.5 months.

SECONDARY OBJECTIVES:

I. To determine whether this drug may inhibit the activation of peripheral blood T cells analyzed ex vivo.

OUTLINE:

Patients receive saracatinib orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity.

Inclusion criteria

• Histologically or cytologically confirmed metastatic melanoma

• Stage IV or unresectable stage III disease
• Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral computed tomography (CT) scan
• No known brain metastases
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Life expectancy > 12 weeks
• White blood cell (WBC) ≥ 3,000/mcL
• Absolute neutrophil count (ANC) ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Hemoglobin ≥ 9 g/dL
• Total bilirubin normal
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times upper limit of normal
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• Proteinuria ≤ 1+ by dipstick OR 24-hour urine protein ≤ 1 g
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception prior to study until completion of study treatment
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD0530
• No QTc prolongation (defined as a QTc interval ≥ 480 msecs) or other significant electrocardiogram (ECG) abnormalities
• No poorly controlled hypertension (e.g., systolic blood pressure [BP] of ≥ 140 mm Hg or diastolic BP of ≥ 90 mm Hg)
• No condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation), prior surgical procedures affecting absorption, or active peptic ulcer disease that impairs the ability to swallow AZD0530 tablets
• No intercurrent cardiac dysfunction including, but not limited to, any of the following:

• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• No recent history of ischemic heart disease including myocardial infarction
• No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
• No other malignancy within the past 5 years, except definitively treated, localized, nonmelanoma skin cancer or low-grade cervical neoplasm
• At least 4 weeks since prior and no more than one prior treatment regimen for advanced disease
• No prior kinase inhibitor with activity against Src kinases for metastatic melanoma
• More than 4 weeks since prior luteinizing hormone-releasing hormone agonists
• No concurrent combination antiretroviral therapy for human immunodeficiency virus (HIV)-positive patients
• No concurrent prohibited cytochrome P450 3A4 (CYP3A4)-active agents or substances

• Prohibited drugs should be discontinued 7 days prior to the administration of the first dose of AZD0530 and for 7 days following discontinuation of AZD0530
• No other concurrent investigational agents or commercial therapies