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

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Stage IIB Melanoma

Stage IIC Melanoma

Recurrent Melanoma

Stage IIA Melanoma

Stage IV Melanoma

Treatments

Drug: saracatinib

Study type

Interventional

Funder types

NIH

Identifiers

NCT00669019

CDR0000594729 (Registry Identifier)

16077A

N01CM62201 (U.S. NIH Grant/Contract)

NCI-2009-00193

Details and patient eligibility

About

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

Full description

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.

Enrollment

23 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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