Low-Dose Radiation Therapy to the Whole Liver With Gemcitabine and Cisplatin in IHC
Condition: Intrahepatic Cholangiocarcinoma
MeSH terms: Cholangiocarcinoma
Intervention: Gemcitabine; Cisplatin; low dose radiotherapy
Intervention description: Whole liver and portal lymph node basin low dose radiotherapy
Intervention MeSH terms: Gemcitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: low-dose radiotherapy; gemcitabine; cisplatin; cholangiocarcinoma

Summary:

      The overall goal of this study is to determine the safety and efficacy of combination
      treatment of low-dose fractionated radiation therapy with gemcitabine-cisplatin chemotherapy
      for locally advanced mass forming intra-hepatic cholangiocarcinoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologic diagnosis of mass-forming IHC. OR

          -  Histologic diagnosis of adenocarcinoma of the liver in setting of negative
             colonoscopy, upper endoscopy, mammography (females), or cross-sectional imaging for
             primary disease.

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension as ≥10 mm (≥1 cm) with spiral CT scan,
             MRI. See Section 8 for the evaluation of measurable disease.

          -  Locally advanced disease (portal lymph node disease, multifocal intrahepatic lesions,
             or major vascular invasion) AND no evidence of omental, peritoneal, or pelvic
             metastases.

          -  Other sites of metastatic disease (e.g. lung, distant lymph nodes, bone) are allowed.

          -  No prior chemotherapy, radiotherapy, or surgical therapy.

          -  ECOG performance status ≤ 1 (Karnofsky ≥70%). See Appendix A.

          -  Life expectancy of greater than six months.

          -  Patients must have normal organ and marrow function as defined below:

          -  leukocytes≥3,000/mcL

          -  absolute neutrophil count≥1,500/mcL

          -  platelets ≥100,000/mcL

          -  hemoglobin≥9.0 g/dL

          -  total bilirubin≤2.0 mg/dL

          -  AST(SGOT)/ALT(SGPT)≤3 × institutional upper limit of normal

          -  creatinine within normal institutional limits OR

          -  creatinine clearance≥60 mL/min/1.73 m2 for patients with creatinine levels above
             institutional normal

          -  int'l normalized ratio<1.8

          -  systolic blood pressure≤160 mmHg

          -  diastolic blood pressure ≥90 mmHg

          -  For women of child-bearing potential, negative serum pregnancy test within 14 days
             prior to registration.

          -  Women of childbearing age and male participants.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Prior chemotherapy, surgical therapy, or radiotherapy for IHC.

          -  Patients who are receiving any other investigational agents or have been treated with
             any other therapeutic clinical protocols within 30 days prior to study entry or during
             participation in the study.

          -  Patients with known brain metastases will 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 gemcitabine or cisplatin.

          -  Prior invasive malignancy (except for non-melanomatous skin cancer, low grade prostate
             cancer, and in situ cervical cancer) unless disease free for ≥ two years.

          -  Periductal infiltrating, intraductal, or poorly differentiated neuroendocrine (e.g.
             high grade, small, or large cell) tumor histology.

          -  Prior abdominal radiotherapy.

          -  Cirrhosis, primary sclerosing cholangitis, hepatitis viral infection (documented by
             positive serology and antigen serologic testing), or other background liver diseases.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection; unstable angina and/or congestive heart failure within the last 6 months;
             transmural myocardial infarction within the last 6 months; New York Heart Association
             grade II or greater congestive heart failure requiring hospitalization within 12
             months prior to registration; history of stroke, cerebral vascular accident or
             transient ischemic attack within 6 months; serious and inadequately controlled cardiac
             arrhythmia; significant vascular disease (e.g.;, high risk aortic aneurysm, history of
             aortic dissection) or clinically significant peripheral vascular disease; evidence of
             bleeding diathesis or coagulopathy; serious or non-healing wound, ulcer, or bone
             fracture or history of abdominal fistula, gastrointestinal perforation or
             intra-abdominal abscess, major surgical procedure or significant traumatic injury
             within 28 days prior to registration; bacterial or fungal infection requiring
             intravenous antibiotics at the time of registration; chronic obstructive pulmonary
             disease exacerbation or other respiratory illness requiring hospitalization or
             precluding study therapy at the time of registration; active connective tissue
             disorders, such as lupus or scleroderma, that in the opinion of the treating physician
             may put the patient at high risk for radiation toxicity; any other major medical
             illnesses or psychiatric impairments that in the investigator's opinion will prevent
             administration or completion of protocol therapy; cognitive impairment that precludes
             a patient from acting as his or her own agent to provide informed consent.

          -  Pregnant or breast feeding women.

          -  Men and women of childbearing potential who are sexually active and not willing/able
             to use medically acceptable forms of contraception.

          -  Acquired immune deficiency syndrome (AIDS) based upon current CDC definition. Note,
             however, that HIV testing is not required for entry into this protocol. The need to
             exclude patients with AIDS from this protocol is necessary because the treatments
             involved in this protocol are significantly immunosuppressive.