RATIONALE: Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: Phase II trial to study the effectiveness of bortezomib in treating patients who have unresectable or metastatic gastric cancer or gastroesophageal junction adenocarcinoma.

OBJECTIVES:

Primary

• Determine the efficacy of bortezomib in patients with unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.

Secondary

• Determine the toxicity of this drug in these patients.
• Determine possible predictors of response to this drug, using pretreatment tumor immunohistochemistry, in these patients.

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

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 15-33 patients will be accrued for this study within 5-12 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma

  • Siewert's class II or III disease

• Measurable disease

  • At least 1 unidimensionally measurable lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

• No history of known or active brain metastases or primary brain tumors

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100% OR
• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• AST and ALT no greater than 3 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)

Renal

• Creatinine no greater than 1.5 mg/dL

Cardiovascular

• No prior cerebrovascular event
• No prior orthostatic hypotension
• No myocardial infarction within the past 6 months
• No peripheral vascular disease requiring surgical management
• No evidence of acute ischemia or significant conduction abnormality by EKG

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 2 months after study participation
• No evidence of peripheral neuropathy
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to bortezomib
• No other malignancy within the past 3 years except basal cell skin cancer, carcinoma in situ of the cervix, or adequately treated nonmetastatic prostate cancer
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study participation
• No other concurrent uncontrolled illness that would preclude study participation
• No other medical condition or reason that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 3 weeks since prior immunotherapy
• No concurrent biological or immunological agents

Chemotherapy

• No more than 1 prior chemotherapy regimen (including adjuvant chemotherapy)
• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• More than 3 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• Not specified

Other

• Recovered from all prior therapy
• No other concurrent investigational agents
• No other concurrent anticancer agent or therapy