Bortezomib, Fluorouracil, and Leucovorin in Treating Patients With Metastatic or Unresectable Stomach Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with fluorouracil and leucovorin may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving bortezomib together with fluorouracil and leucovorin works in treating patients with metastatic or unresectable stomach cancer.

Detailed Description
-----------------
OBJECTIVES: Primary Determine response in patients with previously treated metastatic or unresectable gastric or gastroesophageal junction adenocarcinoma treated with bortezomib, fluorouracil, and leucovorin calcium. Secondary Determine time to progression and overall survival of patients treated with this regimen. Determine the toxic effects of this regimen in these patients. OUTLINE: This is a non-randomized, multicenter study. Patients receive bortezomib IV over 3-5 seconds on days 1, 8, and 15. One hour after completion of bortezomib, patients receive leucovorin calcium IV and fluorouracil IV followed by fluorouracil IV continuously over 46 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for survival. PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study.

Official Title
-----------------
A Phase II Combination Trial of PS-341 and 5-FU/LV in Gastric and/or GE Junction Adenocarcinoma

Conditions
-----------------
Gastric Cancer

Intervention / Treatment
-----------------
* Drug: bortezomib
* Drug: fluorouracil
* Drug: leucovorin calcium


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Diagnosis of gastric or gastroesophageal junction adenocarcinoma Metastatic or unresectable disease Progressive disease after receiving 1 prior chemotherapy regimen for metastatic disease comprising 1 of the following: Fluorouracil Cisplatin and irinotecan Capecitabine Taxanes Measurable disease No esophageal cancer No brain metastases PATIENT CHARACTERISTICS: Age Over 18 Performance status ECOG 0-2 OR Karnofsky 60-100% Life expectancy At least 3 months Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin normal AST and ALT ≤ 2.5 times upper limit of normal Renal Creatinine ≤ 1.5 mg/dL Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No acute ischemia by EKG No significant conduction abnormality by EKG, including either of the following: Bifasicular block, defined as left anterior hemiblock in the presence of right bundle branch block Second or third degree atrioventricular block No history of cardiac or cerebrovascular disease due to hypotension and tachycardia Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception before, during, and for 6 months after study participation No ongoing or active infection No other uncontrolled illness No peripheral neuropathy ≥ grade 2 within the past 2 weeks No allergy to boron or mannitol PRIOR CONCURRENT THERAPY: Biologic therapy More than 4 weeks since prior immunotherapy Chemotherapy More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered Endocrine therapy Not specified Radiotherapy More than 4 weeks since prior radiotherapy and recovered Surgery More than 2 weeks since prior major surgery Other No concurrent highly active anti-retroviral therapy for HIV-positive patients No other concurrent investigational agents

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: bortezomib|nan|
|Drug: fluorouracil|nan|
|Drug: leucovorin calcium|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate as measured by RECIST every 8 weeks |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression every 8 weeks |  |  | 
| Overall survival |  |  | 
| Toxicity every 4 weeks |  |  | 
| Molecular correlates on and off study treatment |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent gastric cancer, stage IV gastric cancer, adenocarcinoma of the stomach