Recurrent Melanoma, Stage IIA Melanoma, Stage IIB Melanoma, Stage IIC Melanoma, Stage IV Melanoma
Conditions
Brief summary
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
Detailed 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.
Interventions
DRUGsaracatinib
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Up to 25 weeks | Response will be evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST). A sum of the longest diameter (LD) for all target lesions will be calculated and reported as the baseline sum LD. The baseline sum LD will be used as reference by which to characterize the objective tumor response. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum LD; Objective response = CR + PR. CT scans will be performed at baseline and every 4-8 weeks while on study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Up to 2 years | Progression will be evaluated in this study using the RECIST criteria (the appearance of new lesions and/or at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study). Progression-free survival time was calculated as the time from treatment start to date of progression or death, whichever comes first. |
Countries
United States
Participant flow
Recruitment details
Patients were enrolled at five sites in the United States between August 2008 and September 2009.
Participants by arm
| Arm | Count |
|---|---|
| Saracatinib Patients receive saracatinib 175 mg oral once daily in the absence of disease progression or unacceptable toxicity. | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | Saracatinib |
|---|---|
| Age, Continuous | 63 years |
| Performance Status 0 | 13 participants |
| Performance Status 1 | 10 participants |
| Region of Enrollment United States | 23 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 23 / 23 |
| serious Total, serious adverse events | 1 / 23 |
Outcome results
Primary
Objective Response Rate
Response will be evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST). A sum of the longest diameter (LD) for all target lesions will be calculated and reported as the baseline sum LD. The baseline sum LD will be used as reference by which to characterize the objective tumor response. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum LD; Objective response = CR + PR. CT scans will be performed at baseline and every 4-8 weeks while on study.
Time frame: Up to 25 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saracatinib | Objective Response Rate | 0 percentage of participants |
Secondary
Progression-free Survival
Progression will be evaluated in this study using the RECIST criteria (the appearance of new lesions and/or at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study). Progression-free survival time was calculated as the time from treatment start to date of progression or death, whichever comes first.
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Saracatinib | Progression-free Survival | 7.4 weeks |