Gemcitabine With or Without Capecitabine and/or Radiation Therapy or Gemcitabine With or Without Erlotinib in Treating Patients With Locally Advanced Pancreatic Cancer That Cannot Be Removed by Surgery
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as gemcitabine and capecitabine, work in
      different ways to stop the growth of tumor cells, either by killing the cells or by stopping
      them from dividing. Erlotinib may stop the growth of tumor cells by blocking some of the
      enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor
      cells. It is not yet known which regimen of chemotherapy with or without erlotinib and/or
      radiation therapy is most effective in treating pancreatic cancer.

      PURPOSE: This randomized phase III trial is studying giving gemcitabine together with or
      without capecitabine and/or radiation therapy to see how well it works compared with giving
      gemcitabine together with or without erlotinib in treating patients with locally advanced
      pancreatic cancer that cannot be removed by surgery.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To assess whether administrating chemoradiotherapy in patients whose tumor is controlled
           after 4 months of induction chemotherapy (CT) increases survival compared with
           continuation of the same CT in patients with unresectable, locally advanced
           adenocarcinoma of the pancreas.

      Secondary

        -  To assess whether erlotinib hydrochloride combined with gemcitabine hydrochloride and
           administered as maintenance treatment increases progression-free survival compared with
           gemcitabine hydrochloride alone and without maintenance treatment.

        -  To evaluate the response rate in the CT and chemoradiotherapy (CRT) arms.

        -  To evaluate tolerance to erlotinib hydrochloride as maintenance treatment after the end
           of CT or CRT.

        -  To study the predictive molecular factors (i.e., survivin, K-ras, EGFR, PTEN, or AKT) of
           survival.

      OUTLINE: This is a multicenter study. Patients in the first randomization are stratified
      according to center and ECOG performance status (0-1 vs 2). Patients in the second
      randomization are stratified according to center and initial treatment arm (I vs II).

        -  First randomization: Patients are randomized to 1 of 2 treatment arms.

             -  Arm I: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8,
                15, 22, 29, 36, and 43. Following the first evaluation, patients continue to
                receive gemcitabine hydrochloride on days 57, 64, 71, 85, 92, and 99 for a total of
                4 months.

             -  Arm II: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8,
                15, 22, 29, 36, and 43. Following the first evaluation, patients continue to
                receive gemcitabine hydrochloride on days 57, 64, 71, 85, 92, and 99. Patients also
                receive oral erlotinib hydrochloride once daily for 4 months.

      After completion of treatment in the first randomization proceed to the second randomization.

        -  Second randomization: Patients are randomized to 1 of 4 treatment arms.

             -  Arm I: Patients continue gemcitabine hydrochloride as in arm I in the first
                randomization on days 113, 120, and 127 and on days 141, 148, and 155 for 2 months
                in the absence of disease progression.

             -  Arm II: Patients continue gemcitabine hydrochloride as in arm II in the first
                randomization on days 113, 120, and 127 and on days 141, 148, and 155 and oral
                erlotinib hydrochloride daily for 2 months followed by erlotinib hydrochloride
                alone as maintenance therapy in the absence of disease progression.

             -  Arm III: Patients receive oral capecitabine twice daily and undergo radiotherapy
                beginning on day 127, 5 days a week, for 6 weeks, in the absence of disease
                progression.

             -  Arm IV: Patients receive oral capecitabine twice daily and undergo radiotherapy
                beginning on day 127, 5 days a week, for 6 weeks. Beginning 15 days after
                completion of CRT, patients receive a reintroduction of oral erlotinib
                hydrochloride alone once daily in the absence of disease progression or
                unacceptable toxicity.

      Tumor tissue will be analyzed for the relationship between biological markers and resistance
      to treatment.

      After completion of study treatment, patients are followed every 2 months.
    

Intervention name(s): capecitabine; erlotinib hydrochloride; gemcitabine hydrochloride; laboratory biomarker analysis; radiation therapy
Intervention type(s): Drug; Drug; Drug; Other; Radiation
Intervention MeSH terms: Gemcitabine; Capecitabine; Erlotinib Hydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adenocarcinoma of the pancreas; stage III pancreatic cancer