Oxaliplatin and Capecitabine in Patients With Unresectable Cholangiocarcinoma
Condition: Cancer of the Gallbladder; Cancer of the Biliary Tract
MeSH terms: Cholangiocarcinoma; Gallbladder Neoplasms; Biliary Tract Neoplasms
Intervention: Capecitabine; Oxaliplatin
Intervention description: 1500 mg/m^2 PO twice daily x 14 days.; 130 mg/m^2 IV over 2 hours on day 1 of 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: 44.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gastrointestinal; Capecitabine; Oxaliplatin; Carcinoma of the Gallbladder; Carcinoma of the Intrahepatic or Extrahepatic Biliary Tract; Xeloda; Eloxatin

Summary:

      This is a Phase II trial of the combination of oxaliplatin (Eloxatin) and capecitabine
      (Xeloda), known as XELOX, in participants with unresectable or recurrent cholangiocarcinoma,
      including carcinoma of the gallbladder or biliary tract, both intrahepatic and extrahepatic.
      Participants may be either previously untreated or treated with chemotherapy. Participants
      will accrue to two strata based on pre-treatment status; separate response rates and
      statistical operating characteristics will be applied to each stratum.

      The primary objective is to determine the objective response rate (complete plus partial) of
      XELOX in this population.

      Secondary objectives include determining toxicity, stable disease rates, and median and
      overall survival of participants treated with this combination.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must have histologically confirmed carcinoma of the gallbladder,
             intrahepatic or extrahepatic biliary tract, not amenable to resection with curative
             intent.

          -  Participants must have measurable disease as per the modified Response Evaluation
             Criteria In Solid Tumors (RECIST) criteria, defined as at least one lesion that can be
             accurately measured in at least one dimension, with minimum lesion size equal to or
             more than twice the slice thickness of the imaging study used.

          -  Participants who are previously untreated as well as those who have received prior
             therapy are eligible to participate in this study. Participants may have received up
             to a total of two prior chemotherapy regimens for their disease, including biologic
             therapy(ies). The same regimen may have been received at different times during the
             course of the Participant's treatment. Surgery, radiofrequency ablation, external beam
             radiotherapy, or other directed therapies do not count as prior regimens and are
             allowed.

          -  Previous treatment may include systemic chemotherapy, however, prior capecitabine
             (unless administered as a radiosensitizing agent concurrently with prior external beam
             radiotherapy) or oxaliplatin are excluded.

          -  If radiation was previously received, the measurable disease must be recurrent or
             metastatic disease outside the previous radiation field.

          -  A minimum of 4 weeks must have elapsed since completion of any prior chemotherapy or
             radiotherapy.

          -  Participants should have a life expectancy of at least 16 weeks based on the clinical
             judgment of the Investigator.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of </= 2 or Karnofsky >
             70.

          -  Adequate bone marrow function defined as absolute peripheral granulocyte count of >/=
             1500/mm3, platelet count >/= 100,000/ mm3, and hemoglobin >/= 10 gm/dL.

          -  Adequate renal function, defined as serum creatinine </= 1.5 times ULN institutional
             normal and calculated creatinine clearance >30 mL/min (using Cockcroft and Gault
             formula).

          -  Participants must have adequate hepatic function: total bilirubin </= 2.0 gm/dL; serum
             albumin >/= 2.5 gm/dL; transaminases up to 5 times the upper limit of institutional
             normal value; or prothrombin time prolonged up to 2 seconds greater than the
             institutional normal value.

          -  Negative serum pregnancy test in women with childbearing potential.

          -  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.

          -  Participants must sign an Informed Consent and Authorization indicating that they are
             aware of the investigational nature of this study and the known risks involved.

          -  Age >/=18 years.

          -  Participants taking therapeutic dose-levels of coumarin-derivate anticoagulants should
             be switched to low Low molecular weight heparin (LMWH). Low-dose coumadin (e.g. 1 mg
             po per day) in Participants with in-dwelling venous access devices, is allowed.

        Exclusion Criteria:

          -  Prior therapy with oxaliplatin or capecitabine; capecitabine administered as a
             radiosensitizing agent concurrently with prior external beam radiotherapy is
             allowable.

          -  Participants 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.

          -  Participants may not be receiving any other investigational agents nor have received
             any investigational drug </= 30 days prior to enrollment.

          -  Participants 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.

          -  Gastrointestinal tract disease resulting in an inability to take oral medication or a
             requirement for IV alimentation, prior surgical therapy affecting absorption.

          -  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.

          -  Because Participants with immune deficiency are at increased risk of lethal infections
             when treated with marrow-suppressive therapy, HIV-positive Participants receiving
             combination anti-retroviral therapy are excluded from the study because of possible
             pharmacokinetic interactions with XELOX. Appropriate studies will be undertaken in
             Participants receiving combination anti-retroviral therapy when indicated.

          -  Participants with extensive symptomatic fibrosis of the lungs.

          -  Peripheral neuropathy > grade 1.

          -  Known DPD deficiency.

          -  Participants receiving therapeutic doses of coumarin-derivative anticoagulant therapy
             are excluded since a drug interaction between capecitabine and coumarin anticoagulants
             has been reported. Participants requiring anticoagulation who may be safely switched
             to LMWH are eligible.