Saracatinib in Treating Patients With Locally Advanced or Metastatic Stomach or Gastroesophageal Junction Cancer

PRIMARY OBJECTIVES:

I. To assess the objective disease control rate (i.e., partial or complete response as
defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria or stable disease
for ≥ 16 weeks) in patients with locally advanced or metastatic adenocarcinoma of the stomach
or gastroesophageal junction treated with AZD0530 (saracatinib).

SECONDARY OBJECTIVES:

I. To assess the median time to disease progression, median overall survival, and 1-year
survival rate in these patients.

II. To assess the toxicity of AZD0530 in these patients. III. To evaluate potential
predictive markers by assessing pretreatment intratumoral levels of src, Y419 phospho-src
(P-Src), and c-terminal src kinase (Csk) in archival tumor biopsies.

OUTLINE:

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

After completion of study treatment, patients are followed up at least every 2 months.

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