Bortezomib With or Without Irinotecan in Treating Patients With Cancer of the Gastroesophageal Junction or Stomach
Condition: Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer
MeSH terms: Adenocarcinoma; Stomach Neoplasms; Esophageal Neoplasms
Intervention: bortezomib; irinotecan
Intervention description: Given IV; Given IV
Intervention MeSH terms: Irinotecan; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

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