RATIONALE: Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy such as irinotecan use different ways to stop tumor cells from dividing so they stop growing or die. Combining bortezomib with irinotecan may kill more tumor cells.

PURPOSE: This phase II trial is studying how well bortezomib with or without irinotecan works in treating patients with gastroesophageal junction or stomach cancer that can not be removed by surgery.

OBJECTIVES:

• Determine the response rate in patients with previously untreated adenocarcinoma of the gastroesophageal junction or stomach when treated with bortezomib and irinotecan.
• Determine the response rate in patients with previously treated (closed to accrual as of 9/19/2006) adenocarcinoma of the gastroesophageal junction or stomach when treated with bortezomib.
• Compare the toxic effects and recovery from these effects in patients treated with these regimens.

OUTLINE: Patients are stratified (stratum 2 closed to accrual as of 9/19/2006) according to prior chemotherapy for advanced disease (yes vs no).

• Stratum 1 (Previously untreated patients): Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and irinotecan IV over 90 minutes on days 1 and 8.
• Stratum 2 (Previously treated patients) (closed to accrual as of 9/19/2006): Patients receive bortezomib as in stratum 1.

In both strata, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 33-58 patients (18-33 previously untreated patients and 15-25 previously treated patients [(closed to accrual as of 9/19/2006)]) will be accrued for this study within 12 months.

• Drug: bortezomib
• Drug: irinotecan hydrochloride

• Experimental: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and irinotecan IV over 90 minutes on days 1 and 8.
• Experimental: Patients receive bortezomib as in stratum 1.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the gastroesophageal junction or stomach

  • Unresectable disease
• Unidimensionally measurable disease defined as at least 1 lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 6 weeks

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin normal
• AST/ALT no greater than 2.5 times upper limit of normal

Renal

• Creatinine normal

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior allergic reactions attributed to compounds of similar chemical or biological composition to bortezomib or other agents in study
• No other malignancy within the past 5 years except early stage squamous cell skin cancer or carcinoma of the cervix that can be treated locally
• No psychiatric illness or social situation that would preclude study compliance
• No ongoing active infection
• No other concurrent uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• Prior adjuvant chemotherapy for resected disease allowed
• No more than 1 prior systemic chemotherapy regimen for advanced disease
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery

• See Chemotherapy

Other

• More than 4 weeks since prior photodynamic therapy (except for relieving esophageal obstruction that could not be treated with laser, stent, or dilation)
• No concurrent photodynamic therapy
• No concurrent commercial or other investigational agents or therapies intended to treat the malignancy
• No concurrent combination antiretroviral therapy for HIV-positive patients