Gemcitabine and Radiation Therapy in Treating Patients With Locally Advanced Upper Gastrointestinal Cancer
Condition: Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Pancreatic Cancer; Small Intestine Cancer
MeSH terms: Pancreatic Neoplasms; Stomach Neoplasms; Gallbladder Neoplasms; Bile Duct Neoplasms; Cholangiocarcinoma; Intestinal Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop
      the growth of tumor cells, either by killing the cells or by stopping them from dividing.
      Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy together
      with radiation therapy may kill more tumor cells.

      PURPOSE: This phase I trial is studying the side effects and best dose of gemcitabine when
      given together with radiation therapy in treating patients with locally advanced upper
      gastrointestinal cancer.
    

Detailed description: 
      OBJECTIVES:

        -  To determine the feasibility of combining preoperative or intraoperative gemcitabine
           hydrochloride with intraoperative radiotherapy.

        -  To determine the tolerance of gemcitabine hydrochloride given concurrently with
           external-beam radiotherapy.

        -  To measure biochemical parameters in tumors that may correlate with the effectiveness of
           therapy.

      OUTLINE: Patients receive gemcitabine hydrochloride IV 12-18 hours prior to planned surgery.
      All patients then undergo an exploratory laparotomy that may include tumor debulking,
      Whipple-type resection (pancreaticoduodenectomy), total pancreatectomy, gastrojejunostomy,
      total or partial gastrectomy, or cholecystectomy and en bloc resection depending on the
      extent of the disease. Patients with no metastatic disease beyond regional lymph nodes also
      undergo intraoperative radiotherapy.

      Beginning 2-6 weeks after surgery, patients undergo external-beam radiotherapy (EBRT) once a
      day 5 days a week for up to 7 weeks. Patients also receive escalating doses of gemcitabine
      hydrochloride IV at the beginning of each week of EBRT.

      Patients undergo tissue sample collection periodically for correlative studies. Samples are
      analyzed for thymidylate synthase (TS), ribonucleotide reductase (RR),
      excision-repair-cross-complementing (ERCC)-1 protein, deoxycytidine kinase mRNA. Biopsy
      tissues are also analyzed for gemcitabine triphosphate, dATP, and dCTP content. p53 status is
      assessed via immunohistochemistry and mRNA levels via quantitative polymerase chain reaction
      (PCR).

      After completion of study treatment, patients are followed every 3 months for 2 years, every
      6 months for 2 years, and then once a year thereafter.
    

Intervention name(s): gemcitabine hydrochloride; polymerase chain reaction; immunohistochemistry staining method; conventional surgery; intraoperative radiation therapy; radiation therapy
Intervention type(s): Drug; Genetic; Other; Procedure; Radiation; Radiation
Intervention MeSH terms: Gemcitabine
Primary purpose: Treatment
Keywords: adenocarcinoma of the extrahepatic bile duct; adenocarcinoma of the gallbladder; adenocarcinoma of the pancreas; adenocarcinoma of the stomach; stage I pancreatic cancer; stage II pancreatic cancer; stage III pancreatic cancer; localized extrahepatic bile duct cancer; recurrent extrahepatic bile duct cancer; unresectable extrahepatic bile duct cancer; localized gallbladder cancer; recurrent gallbladder cancer; unresectable gallbladder cancer; recurrent gastric cancer; stage II gastric cancer; stage III gastric cancer; stage IV gastric cancer; stage I gastric cancer; recurrent pancreatic cancer; small intestine adenocarcinoma; stage IV pancreatic cancer