Phase II SBRT & Chemo for Unresectable Cholangiocarcinoma Followed by Liver Transplantation
Condition: Cholangiocarcinoma; Hepatobiliary Neoplasm; Liver Cancer; Bile Duct Cancer; Cancer of Gallbladder
MeSH terms: Cholangiocarcinoma; Bile Duct Neoplasms; Gallbladder Neoplasms
Intervention: Stereotactic Body Radiotherapy; Gemcitabine; Cisplatin; Carboplatin; Capecitabine; 5FU; Liver transplantation
Intervention description: Standard of care; 100 mg/m2, IV; 25 mg/m2, IV; AUC 2, based on Calvert formula, IV; 1000 mg/m2, PO; 200 mg/m2
Intervention MeSH terms: Cisplatin; Carboplatin; Gemcitabine; Capecitabine; Fluorouracil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine progression-free survival at 12 months for
      stereotactic body radiotherapy (SBRT) and chemotherapy for unresectable hilar
      cholangiocarcinoma (CCA).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of cholangiocarcinoma by any of the below:

               -  Positive transcatheter biopsy or brush cytology

               -  CA 19-9 &#8805; 100mg/mL with a malignant-appearing stricture on cholangiography

               -  Biliary ploidy by fluorescent in situ hybridization with a malignant stricture on
                  cholangiography

          -  Liver tumors not to exceed 8 cm in greatest axial dimension (800 cc of uninvolved
             liver)

          -  Unresectable tumor above cystic duct

          -  Hepatic lesion in patients for whom surgical resection is not possible or would not
             result in an opportunity for cure by any of the below:

               -  Bilateral segmental ductal extension

               -  Encasement of the main portal vein

               -  Unilateral segmental ductal extension with contralateral vascular encasement

               -  Unilateral atrophy with either contralateral segmental ductal or vascular
                  (hepatic artery, portal vein) involvement

          -  Ascites is allowed if the Model for End-Stage Liver Disease (MELD) score is <15[1]

          -  Age > 18 years old

          -  Eastern Clinical Oncology Group performance status 0, 1 or 2 (Appendix 1)

          -  Lab values within 2 wks prior to randomization:

               -  See STUDY SCHEMA for specific blood count inclusion criteria: ANC &#8805; 500 x
                  109/L (&#8805; 1500/mm3), Platelets &#8805; 5 x 109/L (&#8805; 50,000/mm3), Hgb
                  &#8805; 9g/dL

               -  Adequate liver function: Total bilirubin &#8804;1.5 x upper limit of normal
                  (ULN); ALT and/or AST & alkaline phosphatase &#8804; 5 x ULN.

               -  Adequate biliary drainage, with no evidence of active uncontrolled infection
                  (patients on antibiotics are eligible).

               -  See STUDY SCHEMA for specific renal function inclusion criteria: Adequate renal
                  function with a calculated GFR &#8805; 40 ml/min. If the calculated GFR is below
                  40 ml/min a 24 hour urine creatinine clearance can be used.

               -  Albumin > 2.5 mg/dL

               -  INR &#8804; 1.5

          -  Life expectancy > 6 months

          -  Capable of giving written informed consent

        Exclusion Criteria:

          -  Prior radiotherapy to the upper abdomen

          -  Contraindication to receiving radiotherapy

          -  Prior chemotherapy

          -  Prior biliary resection or attempted resection

          -  Prior transperitoneal biopsy

          -  Large esophageal varices without band ligation

          -  Active GI bleed or within 2 weeks of study enrollment

          -  Ascites refractory to medical therapy or shunting

          -  Active/unresolved biliary tract obstruction

          -  Presence of multifocal, lymphatic, or extrahepatic metastases

          -  Participation in another concurrent treatment protocol

          -  If history of other primary cancer, subject eligible only if she or he has:

               -  Curatively resected non-melanomatous skin cancer

               -  Curatively treated cervical carcinoma in situ

               -  Other primary solid tumor curatively treated with no known active disease present
                  and no treatment administered for the last 3 years

          -  Any evidence of severe or uncontrolled systemic diseases or laboratory finding that in
             the view of the investigator makes it undesirable for the patient to participate in
             the trial

          -  Any psychiatric or other disorder (eg brain metastases) likely to impact on informed
             consent

          -  Pregnancy or breast-feeding

          -  While not excluded, patients with significant impaired hearing must be made aware of
             potential ototoxicity and may choose not to be included. If included, baseline
             audiograms are recommended and, in those given cisplatin, should be followed by repeat
             audiograms prior to cycle 2.