A Phase 2 Study of AZD0530 in Patients With Metastatic or Locally Advanced Gastric Carcinoma

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

- 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