Bevacizumab and Combination Chemotherapy Before Surgery in Treating Patients With Locally Advanced Esophageal or Stomach Cancer
Condition: Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Squamous Cell Carcinoma of the Esophagus; Stage IA Esophageal Cancer; Stage IA Gastric Cancer; Stage IB Esophageal Cancer; Stage IB Gastric Cancer; Stage IIA Esophageal Cancer; Stage IIA Gastric Cancer; Stage IIB Esophageal Cancer; Stage IIB Gastric Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer
MeSH terms: Adenocarcinoma; Stomach Neoplasms; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma
Intervention: bevacizumab; oxaliplatin; leucovorin calcium; fluorouracil; therapeutic conventional surgery; laboratory biomarker analysis
Intervention description: Given IV; Given IV; Given IV; Given IV; Undergo surgical resection; Correlative studies
Intervention MeSH terms: Leucovorin; Bevacizumab; Antineoplastic Agents, Immunological; Fluorouracil; Oxaliplatin; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This pilot phase II trial studies how well giving bevacizumab and combination chemotherapy
      together before surgery works in treating patients with locally advanced esophageal or
      stomach cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in
      different ways. Some block the ability of tumor cells to grow and spread. Others find tumor
      cells and help kill them or carry tumor-killing substances to them. Drugs used in
      chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin work in different
      ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Giving bevacizumab and combination chemotherapy before surgery may make the tumor
      smaller and reduce the amount of normal tissue that needs to be removed. Giving these
      treatments after surgery may kill any tumor cells that remain after surgery.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have biopsy proven adenocarcinoma, squamous cell carcinoma or
             undifferentiated carcinoma of the esophagus, GE junction and/or gastric cardia

          -  Patients must have potentially resectable disease by the thoracic, minimally invasive
             or transhiatal approach

               -  No portion of the lesion may be within 5 cm of the cricopharyngeus

               -  Patient must be considered medically fit for surgery with average or below
                  average risk

               -  T1-3 or T4 with local invasion confined to diaphragm, pleura or pericardium

               -  No myocardial infarction within 12 months of enrollment

          -  Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  White blood cells (WBC) >= 3,500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Serum creatinine (Cr) =< 1.5 mg and/or creatinine clearance >= 60 cc/min

          -  Bilirubin must be < upper limit of normal (ULN) unless the patient has a chronic grade
             1 bilirubin elevation due to Gilbert's disease or similar syndrome due to slow
             conjugation of bilirubin

          -  Alkaline phosphatase must be < ULN

          -  Aspartate aminotransferase (AST) & alanine aminotransferase (ALT) must be < ULN

          -  Urine protein/creatinine (UPC) ratio of < 1.0 or dipstick for protein of < 2+, Common
             Terminology Criteria for Adverse Events version 4.0 (CTCAE v 4) grade < 2; patients
             with a UPC ratio >= 1.0 or dipstick of 2+ must undergo a 24-hour urine collection and
             must demonstrate < 1 gm of protein in order to participate

          -  Patients must give written informed consent and Health Insurance Portability and
             Accountability Act (HIPAA) consent

        Exclusion Criteria:

          -  Patients with prior chemotherapy for any malignant disorder, thoracic radiotherapy or
             prior surgical resection of an esophageal tumor are ineligible

          -  Patients with biopsy-proven invasion of the tracheobronchial tree or
             tracheo-esophageal fistula are ineligible

          -  Patients with a history of a curatively treated malignancy must be disease-free for at
             least two years and have a survival prognosis that is greater than five years

          -  Eligible patients of reproductive potential (both sexes) must agree to use an accepted
             and effective method of contraceptive during study therapy and for at least 6 months
             after the completion of bevacizumab; women must not be pregnant or breast-feeding
             because the study drugs administered may cause harm to an unborn fetus or
             breastfeeding child; all females of childbearing potential must have a serum pregnancy
             test to rule out pregnancy within 7 days prior to registration

          -  Patients with a history of hypertension must measure < 150/90 mmHg and be on a stable
             regimen of anti-hypertensive therapy; patients with a history of hypertension who have
             a blood pressure of 150/90 mmHg, or greater are not eligible; patients with a history
             of hypertension who have a blood pressure of < 150/90 mmHg but are not on a stable
             regimen of anti-hypertensive therapy, are not eligible

          -  Any prior history of hypertensive crisis or hypertensive encephalopathy

          -  New York Association (NYHA) grade II or greater congestive heart failure

          -  Patients must not have a serious or non-healing wound, skin ulcers or unhealed bone
             fracture, or known human immunodeficiency virus (HIV) infection

          -  Patients with >= grade 2 neuropathy are not eligible

          -  Patients must not have had significant traumatic injury within 28 days prior to
             randomization

          -  Patients with PT (INR) > 1.5 are not eligible; the patient may not be receiving
             full-dose anticoagulation; prophylactic or full dose anticoagulation are permitted
             post-resection or for treatment of an intercurrent thrombotic event

          -  Patients with non-malignant systemic disease (cardiovascular, renal, hepatic, etc.)
             that would preclude any of the study therapy drugs are not eligible; specifically
             excluded are the following conditions: current symptomatic arrhythmia, symptomatic
             peripheral vascular disease

          -  Patients with a history of the following within 12 months of study entry are not
             eligible: arterial thromboembolic events, unstable angina

          -  Any history of stroke or transient ischemic attack

          -  Significant vascular disease (i.e. aortic dissection, aortic aneurysm)

          -  Patients with psychiatric or addictive disorders or other conditions that, in the
             opinion of the investigator, would preclude them from meeting the study requirements
             are not eligible

          -  Distant metastases

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to study enrollment

          -  Known hypersensitivity to any component of bevacizumab