A Multicenter, Open-Label, Phase II Study of Irinotecan, Cisplatin, and Bevacizumab in Patients With Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Inclusion Criteria:

- Histologically or cytologically confirmed gastric or gastroesophageal junction (GEJ)
adenocarcinoma

- Metastatic or unresectable disease

- Siewert's classification I, II, or III

- No ulcerated, non-healing tumors or tumors that have developed a malignant fistula

- No esophageal tumors

- No known or active brain metastases

- Performance status - Karnofsky 60-100%

- Performance status - ECOG 0-2

- Neutrophil count >= 1,500/mm^3

- Platelet count >= 75,000/mm^3

- No bleeding diathesis or coagulopathy

- Bilirubin =< 1.5 mg/dL

- AST and ALT =< 3 times upper limit of normal (ULN) (5 times ULN if liver metastases
are present)

- PT (INR) =< 1.5

- PTT =< 3 seconds above ULN

- Creatinine =< 1.5 mg/dL

- Proteinuria < 1+

- Protein < 500 mg/24-hour urine collection

- No acute ischemia or significant conduction abnormality by EKG

- No clinically significant cardiovascular disease

- No uncontrolled hypertension (blood pressure > 160/90 mm Hg on medication)

- No myocardial infarction within the past 6 months

- No unstable angina within the past 6 months

- No transient ischemic attack within the past 6 months

- No cerebrovascular accident within the past 6 months

- No other arterial thromboembolic event within the past 6 months

- No New York Heart Association class II-IV congestive heart failure

- No serious cardiac dysrhythmia requiring medication

- No peripheral vascular disease (grade II or greater)

- No history of stroke

- No CNS disease within the past 5 years (e.g., uncontrolled seizures)

- No other concurrent uncontrolled illness

- No ongoing or active infection requiring parental antibiotics on Day 0 of study

- No serious, non-healing wound

- No serious wound healing by secondary intention

- No ulcer

- No bone fracture

- No psychiatric illness or social situation that would preclude study compliance

- No significant traumatic injury within the past 28 days

- No other neoplastic disease within the past 3 years except basal cell skin cancer,
carcinoma in situ of the cervix, or nonmetastatic prostate cancer

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies

- No other medical condition that would preclude study participation

- Not pregnant or nursing

- No nursing during and for 4 months after study participation

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 4 months after study
participation

- More than 8 weeks since prior immunotherapy and recovered

- No other concurrent biologic or immunologic agents

- No other concurrent bevacizumab

- No prior chemotherapy for metastatic disease

- No prior cisplatin or irinotecan

- Prior neoadjuvant and/or adjuvant chemotherapy or chemoradiotherapy allowed

- More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
and recovered

- No other concurrent chemotherapy

- More than 3 weeks since prior radiotherapy and recovered

- No concurrent radiotherapy

- More than 28 days since prior major surgical procedure or open biopsy

- More than 7 days since prior fine needle aspirations or core biopsies

- No concurrent major surgery

- No other concurrent investigational agents

- No other concurrent anticancer therapy

- No concurrent chronic daily aspirin (> 325 mg/day)

- No concurrent nonsteroidal anti-inflammatory medications that would inhibit platelet
function at doses used to treat chronic inflammatory diseases

- Full-dose anticoagulants allowed, provided the following criteria are met:

- INR in range (i.e., 2-3) while on a stable dose of warfarin or low molecular
weight heparin

- No active bleeding or pathologic condition that would confer a high risk of
bleeding (e.g., tumor involving major blood vessels or known varices)

- No concurrent thrombolytic agents

- No concurrent vitamins, antioxidants, herbal preparations, or supplements

- Single tablet multivitamin allowed