Chemoradiation +Gemcitabine +Continuous 5-FU (Fluorouracil) Followed by High Dose Brachytherapy/Stereotactic Radiation Boost in Locally Advanced Intra/Extrahepatic Cholangiocarcinoma
Condition: Cancer
MeSH terms: Cholangiocarcinoma
Intervention: Fluorouracil (5-FU); Brachytherapy or SBRT (Stereotactic body radiation therapy); Gemcitabine
Intervention description: 5-FU Injection,USP (GeneraMedix Inc.) is effective in palliative management of carcinoma (colon, rectum, breast, stomach, pancreas) FDA approved in 1962-NDA (New Drug Application)012209. This study uses 350 mg/m2/day days 1-5 each week of radiation therapy; Patients receive 45 Gy (gray) external beam radiation therapy including the primary tumor and regular lymph nodes (25 fractions over 5 weeks). Within 1 month of external beam radiation therapy, patients will have boost treatment of 20 Gy in 4 fractions, via Ir-192 brachytherapy or SBRT (Stereotactic Body Radiation Therapy).; Pancreatic:Indicated as first line treatment for patients with locally advanced (nonresectable Stage II or III) or metastatic(Stage IV) pancreatic adenocarcinoma.
Ovarian:Gemzar with carboplatin is indicated for treatment of patients with advanced ovarian cancer relapsed 6 months after plat-based therapy.
Breast:Gemzar with paclitaxel is indicated for first line treatment of patients with metastatic breast cancer after failed anthracycline-containing adjuvant chemotherapy, unless anthracyclines.
Non-small cell lung cancer(NSCLC):Gemzar is indicated with cisplatin for first line treatment of patients with inoperable, local advanced (Stage IIIA/IIIB), metastatic (Stage IV) NSCLC.
Intervention MeSH terms: Gemcitabine; Fluorouracil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: intra or extrahepatic cholangiocarcinoma; liver cancer; liver; HCC; EHCC

Summary:

      OBJECTIVES: This study proposes to evaluate the feasibility of delivery of this treatment in
      terms of toxicity. If toxicity is not acceptable, the treatment is not feasible.

      Primary Objectives

        -  To establish a preliminary assessment whether toxicity rates are acceptable in patients
           with locally advanced intra or extrahepatic cholangiocarcinoma when treated with a
           regimen of gemcitabine every two weeks and continuous fluorouracil (5-FU) given
           concurrently with external beam radiation therapy to a total dose of 45 gray(Gy),
           followed by a brachytherapy or Stereotactic Body Radiation Therapy(SBRT) boost.

      Secondary Objectives

        -  To evaluate the overall survival rate, progression free survival rate, tumor response
           rate, local control rate and the rate of distant metastases following gemcitabine and
           continuous 5-FU concurrent with radiation therapy in patients with locally advanced
           intra or extrahepatic cholangiocarcinoma.

        -  To evaluate the rate at which patients with unresectable extrahepatic cholangiocarcinoma
           become resectable following gemcitabine and radiation therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients over age 18

          2. Intra or extrahepatic cholangiocarcinoma confirmed by biopsy/brushings, biliary
             aneuploidy demonstrated by FISH, or elevated CA 19-9 greater than 100 ng/mL in the
             presence of a radiographic malignant stricture

          3. Deemed surgically unresectable by a surgical oncologist

          4. Malignant disease encompassable within a single radiation field

          5. ECOG 0-2

          6. Laboratory values: Hemoglobin ≥ 8.0 (can be transfused to attain this value),
             Granulocytes > 1,500, platelets > 100,000/ul

        Exclusion Criteria:

          1. Chemotherapy within one month of starting radiation therapy

          2. Previous abdominal radiotherapy

          3. Uncontrolled infection or severe active comorbid disease

          4. Previous malignancy in the past five years, excluding nonmelanoma skin cancers and in
             situ cervical, bladder or uterine cancer

          5. Distant metastatic disease (outside regional lymph nodes)

          6. Pregnancy or lactating women