Capecitabine and Oxaliplatin in Adenocarcinoma of the Small Bowel and Ampulla of Vater
Condition: Gastrointestinal Cancer
MeSH terms: Adenocarcinoma; Gastrointestinal Neoplasms
Intervention: Capecitabine; Oxaliplatin
Intervention description: Oral capecitabine 750 mg/m^2 twice daily (total daily dose 1500 mg/m^2) on Days 1-14 in 21 Day Cycle.; 130 mg/m^2 by vein Day 1 over 2 hours in 21 Day Cycle
Intervention MeSH terms: Capecitabine; Oxaliplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gastrointestinal Cancer; Small Bowel Cancer; Ampulla of Vater; Capecitabine; Xeloda; Oxaliplatin; Eloxatin

Summary:

      Primary Objective:

      1. To determine the objective response rate (complete plus partial) to the combination of
      capecitabine (Xeloda) and oxaliplatin (Eloxatin) (XELOX) in patients with adenocarcinoma of
      the small bowel and ampulla of Vater.

      Secondary objectives include determining the toxicity, time-to-treatment failure, and overall
      survival rates in patients treated with this combination.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients must have histologically or cytologically confirmed adenocarcinoma of the
             small bowel or ampulla of Vater that is either unresectable or metastatic.

          2. Patients must have measurable disease as per the modified Response Evaluation Criteria
             In Solid Tumors (RECIST) criteria.

          3. Patients may be previously untreated or have received previous systemic therapy,
             limited to 5-FU/leucovorin or capecitabine, as adjuvant or neoadjuvant therapy or as a
             radiosensitizer. Patients may have received capecitabine or 5-FU administered as a
             radiosensitizing agent concurrently with external beam radiotherapy as preoperative or
             postoperative therapy. Patients may have received capecitabine or 5-FU/leucovorin as
             part of adjuvant chemotherapy.

          4. If radiation was previously received, the measurable disease must be outside the
             previous radiation field.

          5. A minimum of 4 weeks must have elapsed since completion of any prior chemotherapy or
             radiotherapy. A minimum of 4 weeks must have elapsed since any prior surgery.

          6. Eastern Cooperative Oncology Group (ECOG) Performance Status of less than or equal to
             2.

          7. Adequate bone marrow function defined as absolute peripheral granulocyte count of
             greater than or equal to 1500 mm3, platelet count greater than or equal to 1500 mm3,
             and hemoglobin greater than or equal to 10 gm/dL.

          8. Adequate renal function, defined as serum creatinine less than or equal to 1.5 * ULN
             and calculated creatinine clearance >30 mL/min.

          9. Patients must have adequate hepatic function: total bilirubin less than or equal to
             1.5 gm/dL; serum albumin greater than or equal to 2.5 gm/dL. If the patient does not
             have liver metastasis, transaminases may be up to 2 * the ULN. If the patient has
             liver metastasis, transaminases up to 5 * Upper Limit of Normal (ULN) are allowed.

         10. Negative urine or serum pregnancy test in women with childbearing potential, within
             one week prior to initiation of treatment.

         11. The effects of the combination of oxaliplatin and capecitabine 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 and for the duration of study participation. Should a woman become
             pregnant while participating in this study, she should inform her treating physician
             immediately.

         12. 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.

         13. Age greater than or equal to 18 years. Because no dosing or adverse event data are
             currently available on the use of XELOX in patients <18 years of age, children are
             excluded from this study.

         14. Patients taking therapeutic doses of coumarin-derivative anticoagulants should be
             switched to low-molecular-weight heparin (LMWH). Low-dose Coumadin (e.g. 1 mg by mouth
             (PO) per day) in patients with in-dwelling venous access devices is allowed.

        Exclusion Criteria:

          1. Patients with prior exposure to platinum therapy are excluded. Patients who have
             received prior chemotherapy for metastatic disease are excluded.

          2. Patients who have had chemotherapy 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.

          3. Patients may not be receiving any other investigational agents nor have received any
             investigational drug 30 days prior to enrollment.

          4. Patients with known brain metastases are excluded from this clinical trial because of
             their poor prognosis and their risk for progressive neurologic dysfunction that would
             confound the evaluation of neurologic and other adverse events.

          5. Gastrointestinal tract disease resulting in an inability to take oral medication or a
             requirement for IV alimentation. Prior surgical therapy affecting absorption.

          6. 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.

          7. Because patients with immune deficiency are at increased risk of lethal infections
             when treated with marrow-suppressive therapy, HIV-positive patients receiving
             combination anti-retroviral therapy are excluded from the study because of possible
             pharmacokinetic interactions with XELOX. Appropriate studies will be undertaken in
             patients receiving combination anti-retroviral therapy when indicated.

          8. Patients with extensive symptomatic fibrosis of the lungs.

          9. Peripheral neuropathy > grade 1.

         10. Known Dihydropyrimidine dehydrogenase deficiency (DPD deficiency)

         11. Patients receiving therapeutic doses of coumarin-derivative anticoagulant therapy are
             excluded since a drug interaction between capecitabine and coumarin anticoagulants has
             been reported. Patients requiring anticoagulation who may be safely switched to LMWH
             are eligible.