Bortezomib With or Without Irinotecan in Treating Patients With Cancer of the Gastroesophageal Junction or Stomach

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. 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.

PRIMARY OBJECTIVES:

I. To determine the response rate for the combination of irinotecan and PS 341 in patients with previously untreated adenocarcinoma of the stomach or GEJ.

II. To determine the response rate for PS341 in patients with previously treated adenocarcinoma of the stomach or GEJ.

III. To determine the toxicities and recovery from toxicities for patients receiving PS 341 alone or in combination with irinotecan IV. To perform GeneChip analysis on biopsy specimens prior to and subsequent to treatment with PS341 to determine changes in patterns of gene expression

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.

Eligibility Criteria:
Inclusion Criteria:

* Patients must have histologically or cytologically confirmed adenocarcinoma of the GE junction or stomach, which is beyond the scope of surgical resection
* Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral CT scan
* Patients may have received adjuvant therapy for resected disease

  * Patients who have received no prior systemic therapy for advanced disease are eligible to receive PS341 + irinotecan
  * Patients are eligible for PS-341 as a single agent if they have received any number of prior regimens for gastric cancer
* Life expectancy of greater than 6 weeks
* ECOG performance status =\< 2 (Karnofsky \>= 60%)
* Leukocytes \>= 3,000/uL
* Absolute neutrophil count \>= 1,500/uL
* Platelets \>=100,000/uL
* Total bilirubin within normal institutional limits
* AST(SGOT)/ALT(SGPT) =\< 2.5 X institutional upper limit of normal
* Creatinine within normal institutional limits
* When possible, patients will undergo an esophagogastroduodenoscopy (EGD) with biopsy prior to therapy then at 24 hours after starting PS-341
* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
* Patients may not be receiving any other investigational agents, concurrent radiation therapy, or other chemotherapy; patients who have had photodynamic therapy either within 4 weeks of study entry or concurrently are ineligible, unless it was used to relieve esophageal obstruction that could not be treated with laser, stent or dilatation
* Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to PS 341 or other agents used in the study
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with PS341
* HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study
* Patients with a concurrent malignancy are excluded (except for early stage squamous cell carcinoma of the skin or cervix which can be treated locally); patients with an advanced malignancy within the past five years are not eligible; patients with a prior malignancy who have been disease free for five years are eligible