RATIONALE: Drugs used in chemotherapy, such as irinotecan and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as bevacizumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Giving chemotherapy together with a monoclonal antibody may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving irinotecan and cisplatin together with bevacizumab works in treating patients with unresectable or metastatic gastric (stomach) or gastroesophageal junction adenocarcinoma (cancer).

Condition	Treatment or Intervention	Phase
stage III gastric cancer stage IV gastric cancer recurrent gastric cancer adenocarcinoma of the stomach	Drug: bevacizumab  Drug: cisplatin  Drug: irinotecan  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: growth factor antagonist therapy  Procedure: monoclonal antibody therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the efficacy of irinotecan, cisplatin, and bevacizumab, in terms of time to progression, in patients with unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.

Secondary

• Determine other measures of efficacy, including response rate and median and 1-year survival, in patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Correlate CT perfusion imaging results with the efficacy of this regimen, in terms of time to progression, objective response, and survival, in these patients.
• Determine the feasibility of serial serum proteomic assays in predicting response to therapy, in terms of time to progression, objective response, and survival, in patients treated with this regimen.

OUTLINE: This is an open-label, non-randomized, multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive cisplatin IV over 30 minutes followed by irinotecan IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 47 patients will be accrued for this study within 12 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed gastric or gastroesophageal junction (GEJ)* adenocarcinoma
• Metastatic or unresectable disease
• Siewert's classification I, II, or III NOTE: *The GEJ is defined as within 5 cm (proximal or distal) of the anatomical cardia. Tumors centered more than 5 cm proximal to the anatomical cardia are considered esophageal tumors.
• No ulcerated, non-healing tumors or tumors that have developed a malignant fistula
• No esophageal tumors
• No known or active brain metastases

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Karnofsky 60-100% OR
• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 75,000/mm^3
• No bleeding diathesis or coagulopathy

Hepatic

• 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

Renal

• Creatinine ≤ 1.5 mg/dL
• Proteinuria < 1+ OR
• Protein < 500 mg/24-hour urine collection

Cardiovascular

• 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

Other

• 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 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

PRIOR CONCURRENT THERAPY: Biologic therapy

• More than 8 weeks since prior immunotherapy and recovered
• No other concurrent biologic or immunologic agents
• No other concurrent bevacizumab

Chemotherapy

• 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

Endocrine therapy

• Not specified

Radiotherapy

• See Chemotherapy
• More than 3 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery

• 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

Other

• 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
• No recent or concurrent full-dose anticoagulants except as required to maintain patency of preexisting, permanent indwelling IV catheters
• No concurrent thrombolytic agents
• No concurrent vitamins, antioxidants, herbal preparations, or supplements
• Single tablet multivitamin allowed

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
Pennsylvania
      Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15232,  United States; Recruiting
Tennessee
      Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center, Nashville,  Tennessee,  37232-6307,  United States; Recruiting
Canada, Ontario
      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada; Recruiting

Study chairs or principal investigators

Manish A. Shah, MD,  Principal Investigator,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000365463; MSKCC-04021; NCI-6447; NCT00084604
Record last reviewed:  September 2004
Last Updated:  April 5, 2005
Record first received:  June 10, 2004
ClinicalTrials.gov Identifier:  NCT00084604
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08