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: Phase II trial to study the effectiveness of bortezomib with or without irinotecan in treating patients who have unresectable cancer of the gastroesophageal junction or stomach .

Condition	Treatment or Intervention	Phase
adenocarcinoma of the stomach recurrent gastric cancer stage III gastric cancer stage IV gastric cancer	Drug: bortezomib  Drug: irinotecan  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy	Phase II

Further Study Details: 

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 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 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): 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) 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 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

New York
      Albert Einstein Cancer Center at Albert Einstein College of Medicine, Bronx,  New York,  10467,  United States; Recruiting
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States; Recruiting
      Mount Sinai Medical Center, New York,  New York,  10029,  United States; Recruiting
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States; Recruiting
      North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
      NYU Cancer Institute at New York University Medical Center, New York,  New York,  10016,  United States; Recruiting
Pennsylvania
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111-2497,  United States; Recruiting
Canada, Ontario
      Ottawa Regional Cancer Centre at Ottawa Hospital - General Campus, Ottawa,  Ontario,  K1H 1C4,  Canada; Recruiting
      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada; Recruiting

Study chairs or principal investigators

Scott Wadler, MD,  Study Chair,  Cornell University Medical College   

Study ID Numbers:  CDR0000302448; NYWCCC-0103672; NCI-5941; NCT00061932
Record last reviewed:  September 2004
Last Updated:  April 4, 2005
Record first received:  June 5, 2003
ClinicalTrials.gov Identifier:  NCT00061932
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08