Bevacizumab, Capecitabine, and Oxaliplatin in Treating Advanced Small Intestinal or Ampulla of Vater Adenocarcinoma
Condition: Ampulla of Vater Adenocarcinoma; Small Intestinal Adenocarcinoma; Stage III Ampulla of Vater Cancer AJCC v8; Stage III Small Intestinal Adenocarcinoma AJCC v8; Stage IIIA Ampulla of Vater Cancer AJCC v8; Stage IIIA Small Intestinal Adenocarcinoma AJCC v8; Stage IIIB Ampulla of Vater Cancer AJCC v8; Stage IIIB Small Intestinal Adenocarcinoma AJCC v8; Stage IV Ampulla of Vater Cancer AJCC v8; Stage IV Small Intestinal Adenocarcinoma AJCC v8
MeSH terms: Adenocarcinoma
Intervention: Bevacizumab; Capecitabine; Oxaliplatin
Intervention description: Given IV; Given PO; Given CVC
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Capecitabine; Oxaliplatin; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well bevacizumab given with capecitabine and oxaliplatin work
      in treating participants with small bowel or ampulla of Vater adenocarcinoma that has spread
      to other places in the body. Monoclonal antibodies, such as bevacizumab, may interfere with
      the ability of tumor cells to grow and spread. Drugs using in chemotherapy, such as
      capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells,
      either by killing the cells, by stopping them from dividing, or by stopping them from
      spreading. Giving bevacizumab, capecitabine, and oxaliplatin may work better in treating
      participants with small intestinal or ampulla of Vater adenocarcinoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed adenocarcinoma of the small bowel or
             ampulla of Vater

          -  Prior adjuvant chemotherapy (including fluorouracil [5-FU], capecitabine, and
             oxaliplatin) for the treatment of adenocarcinoma of the small bowel or ampulla of
             Vater is allowed if completed >= 52 weeks prior to first dose of study treatment

          -  Prior capecitabine or 5-FU administered as a radio-sensitizing agent concurrently with
             external beam radiotherapy is allowed

          -  Patients must have metastatic disease

          -  A minimum of 4 weeks must have elapsed from completion of any prior chemotherapy or
             radiotherapy or surgery and the start date of study therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

          -  Absolute neutrophil count (ANC) >= 1,500/ul

          -  Platelets >= 100,000/ul

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN)

               -  In patients with known Gilbert's syndrome direct bilirubin =< 1.5 x ULN will be
                  used as organ function criteria, instead of total bilirubin

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 3 x
             ULN

          -  Calculated creatinine clearance (CrCl) > 50 cc/min (calculated using the Cockcroft and
             Gault formula)

          -  Negative serum or urine pregnancy test in women with childbearing potential (defined
             as not post-menopausal for 12 months or no previous surgical sterilization), within
             one week prior to initiation of treatment

          -  Patients must sign an Informed Consent and Authorization indicating that they are
             aware of the investigational nature of this study and the known risks involved

          -  The effects of the combination of CAPOX and bevacizumab on the developing fetus are
             unknown. For this reason, women of childbearing potential and men must agree to use
             adequate contraception (hormonal or barrier method of birth control) prior to study
             entry, for the duration of study participation, and for six months following the
             completion of therapy. Should a woman become pregnant while participating in this
             study, she should inform her treating physician immediately

          -  Because there is an unknown but potential risk for adverse events in nursing infants
             secondary to treatment of the mother with oxaliplatin or capecitabine or bevacizumab,
             breast feeding must be discontinued

        Exclusion Criteria:

          -  Patients who have received prior chemotherapy for their metastatic disease are
             excluded. Chemotherapy if given as a radiation-sensitizer is allowed

          -  Patients may not be receiving any other investigational agents nor have received any
             investigational drug 28 days prior to enrollment

          -  Known history of dihydropyrimidine (DPD) deficiency

          -  Peripheral neuropathy of grade 3 or greater by Common Terminology Criteria for Adverse
             Events (CTCAE) 4.0

          -  Gastrointestinal tract disease resulting in an inability to take oral medication or a
             requirement for IV alimentation

          -  Because of the interaction between coumadin and capecitabine, patients taking
             therapeutic doses of coumadin-derivative anticoagulants are not eligible. Low-dose
             coumadin (e.g. 1 mg PO per day) in patients with in-dwelling venous access devices is
             allowed but increased frequency of international normalized ratio (INR) monitoring is
             recommended

          -  Prior treatment with bevacizumab or known hypersensitivity to any component of
             bevacizumab

          -  Inadequately controlled hypertension (defined as systolic blood pressure >140 mmHg
             and/or diastolic blood pressure > 90 mmHg)

          -  Prior history of hypertensive crisis or hypertensive encephalopathy

          -  Evidence of bleeding diathesis or significant coagulopathy (in the absence of
             therapeutic anticoagulation)

          -  New York Heart Association (NYHA) grade II or greater congestive heart failure

          -  History of myocardial infarction or unstable angina within 6 months prior to day 1

          -  History of stroke or transient ischemic attack within 6 months prior to day 1.

          -  Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or
             recent peripheral arterial thrombosis) within 6 months prior to day 1

          -  History of hemoptysis (>= 1/2 teaspoon of bright red blood per episode) within 1 month
             prior to day 1

          -  History of abdominal fistula or gastrointestinal perforation which must have resolved
             at least 6 months prior to day 1

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to day 1 or anticipation of need for major surgical procedure during the course
             of the study

          -  Core biopsy or other minor surgical procedure excluding placement of a vascular access
             device, within 7 days prior to day 1

          -  Serious, non-healing wound, active ulcer, or untreated bone fracture

          -  Proteinuria at screening as demonstrated by either (1) urine protein:creatinine (UPC)
             ratio of >= 1.0 or (2) urine dipstick for proteinuria >= 2+ (patients discovered to
             have >/= 2+ proteinuria on dipstick urinalysis should undergo a 24 hour urine
             collection and must demonstrate =< 1g of protein in 24 hours to be eligible)

          -  Known central nervous system (CNS) disease, except for treated brain metastasis.
             Treated brain metastases are defined as having no evidence of progression or
             hemorrhage after treatment and no ongoing requirement for dexamethasone, as
             ascertained by clinical examination and brain imaging (magnetic resonance imaging
             [MRI] or computed tomography [CT]) during the screening period. Anticonvulsants
             (stable dose) are allowed. Treatment for brain metastases may include whole brain
             radiotherapy (WBRT), radiosurgery (RS; gamma knife, linear accelerator [LINAC], or
             equivalent) or a combination as deemed appropriate by the treating physician

          -  Patients with CNS metastases treated by neurosurgical resection or brain biopsy
             performed within 3 months prior to day 1 will be excluded

          -  Current, recent (within 4 weeks of the first infusion of this study), or planned
             participation in an experimental drug study other than this study

          -  Pregnancy (positive pregnancy test) or lactation

          -  Active malignancy, other than superficial basal cell and superficial squamous (skin)
             cell, or carcinoma in situ of the cervix, within last five years

          -  Inability to comply with study and/or follow-up procedures

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, or psychiatric illness/social
             situations that would limit adherence with study requirements