Intervention: Saracatinib
Trial phase: Phase 2
SMILES: CN1CCN(CCOc2cc(OC3CCOCC3)c3c(Nc4c(Cl)ccc5c4OCO5)ncnc3c2)CC1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 21
Group description: Patients receive saracatinib PO QD in the absence of disease progression or unacceptable toxicity.

saracatinib

laboratory biomarker analysis: Correlative studies
Eligibility criteria:
Inclusion Criteria:

Histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (GEJ)

Tumors of the GEJ must be sub-specified as type I, II, or III using the Siewert classification

Metastatic or locally advanced disease

Patients with local/regional disease only, must have unresectable 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 > 3 months
Platelet count ≥ 100,000/mm³
Leukocytes ≥ 3,000/mm³
Absolute neutrophil count ≥ 1,500/mm³
Hemoglobin > 9 g/dL
Total bilirubin normal
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 times upper limit of normal
Creatinine normal OR creatinine clearance ≥ 60 mL/min
Urine protein creatinine ratio < 1.0 OR urine protein < 1,000 mg by 24-hour urine collection

Exclusion Criteria:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

No condition that potentially impairs the ability to swallow or absorb AZD0530, including any of the following:

Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
Active peptic ulcer disease
Short gut syndrome
Malabsorption syndrome of any type
Total or partial bowel obstruction
Inability to tolerate oral medications
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD0530
No QTc prolongation (defined as a QTc interval ≥ 460 msec) or other significant electrocardiogram (ECG) abnormalities
No poorly controlled hypertension (i.e., systolic blood pressure [BP] ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg)
No history of ischemic heart disease, including myocardial infarction

No concurrent cardiac dysfunction including, but not limited to, any of the following:

Symptomatic congestive heart failure
Unstable angina pectoris
Cardiac arrhythmia
No other concurrent uncontrolled illness, including ongoing or active infection or psychiatric illness/social situations, that would limit compliance with study requirements

Prior chemotherapy allowed provided it was administered as part of initial curative intent therapy (i.e., neoadjuvant therapy, adjuvant therapy and/or concurrently with radiotherapy) in combination with surgery

At least 4 weeks since prior chemotherapy
At least 4 weeks since prior and no more than 1 line of palliative chemotherapy for advanced disease
At least 4 weeks since prior radiotherapy and recovered
At least 4 weeks since prior major surgery and recovered
No cytochrome 450 3A4 (CYP3A4) active agents or substances for ≥ 7 days before, during, and for ≥ 7 days after completion of study treatment
No other concurrent investigational agents
No other concurrent anticancer therapy
No concurrent combination antiretroviral therapy for human immunodeficiency virus (HIV)-positive patients