Saracatinib in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed By Surgery
Saracatinib in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed By Surgery
This phase II trial is studying how well saracatinib works in treating patients with stage
 III or stage IV melanoma that cannot be removed by surgery. Saracatinib may stop the growth
 of tumor cells by blocking some of the enzymes needed for cell growth
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