• Response rate [ Designated as safety issue: No ]
  

• Gene expression as assessed by microarray at baseline and after completion of study treatment [ Designated as safety issue: No ]
  

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.

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