Gemcitabine, Cisplatin, Epirubicin, and Capecitabine in Treating Patients With Stage I-II Resectable Pancreatic Cancer
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride, cisplatin,
      epirubicin hydrochloride, and capecitabine, work in different ways to stop the growth of
      tumor cells, either by killing the cells or by stopping them from dividing. Giving
      gemcitabine hydrochloride, with or without cisplatin, epirubicin hydrochloride, and
      capecitabine before surgery may make the tumor smaller and reduce the amount of normal tissue
      that needs to be removed. Giving these drugs after surgery may kill any tumor cells that
      remain after surgery.

      PURPOSE: This randomized phase II/III trial is studying how well gemcitabine hydrochloride,
      with or without cisplatin, epirubicin hydrochloride, and capecitabine, works when given
      before and/or after surgery in treating patients with stage I or stage II pancreatic cancer
      that can be removed by surgery.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To assess the proportion of patients who are event-free (defined as disease progression,
           local recurrence, distant metastasis, new tumor, or death) at 1 year after neoadjuvant
           therapy comprising gemcitabine hydrochloride with cisplatin, epirubicin hydrochloride,
           and capecitabine (PEXG), and adjuvant chemotherapy comprising gemcitabine hydrochloride
           or PEXG regimen in patients with resectable stage I or II adenocarcinoma of the
           pancreas. (phase II)

        -  To assess whether the best experimental regimen, which will be selected on the basis of
           the phase II part of the trial, is able to improve overall survival when compared to
           standard adjuvant gemcitabine in these patients. (phase III)

      Secondary

        -  To assess radiological, biochemical, and pathological response rate (neoadjuvant arm
           only) in these patients.

        -  To assess surgical resection rate, surgical mortality and morbidity, and proportion of
           patients with negative surgical margins.

        -  To assess lymph node status in these patients.

        -  To determine tolerability of these regimens in these patients.

      OUTLINE: This is a multicenter study. Patients are stratified according to center. Patients
      are randomized to 1 of 3 treatment arms.

        -  Arm I (adjuvant gemcitabine hydrochloride) : Patients receive gemcitabine hydrochloride
           IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days for 6 months in the
           absence of disease progression or unacceptable toxicity.

        -  Arm II (adjuvant cisplatin, epirubicin hydrochloride, gemcitabine hydrochloride, and
           capecitabine [PEXG regimen]): Patients receive cisplatin IV over 1 hour on days 1-5,
           epirubicin hydrochloride IV on days 1 and 8, gemcitabine hydrochloride IV over 1 hour on
           days 1 and 8, and oral capecitabine on days 1-14. Treatment repeats every 14 days for 6
           months in the absence of disease progression or unacceptable toxicity.

        -  Arm III (neoadjuvant and adjuvant PEXG regimen): Patients receive neoadjuvant cisplatin
           IV over 1 hour on days 1-5, epirubicin hydrochloride IV on days 1 and 8, gemcitabine
           hydrochloride IV over 1 hour on days 1 and 8, and oral capecitabine on days 1-14.
           Treatment repeats every 14 days for up to 3 months. Patients then undergo surgery for
           pancreatic cancer followed by adjuvant (within 2 months of surgery) PEXG given as in
           neoadjuvant therapy. Treatment with adjuvant PEXG repeats every 14 days for 3 months in
           the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 1 year,
      every 4 months for 2 years, and then every 6 months thereafter.
    

Intervention name(s): capecitabine; cisplatin; epirubicin; gemcitabine
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 1250 mg/mq/day per os for 14 days every 14 days for 6 months; 30 mg/mq every 14 days for 6 months; 30 mg/mq every 14 days for 6 months; ARM A: 1000 mg/mq for 3 weekly infusions every 4 weeks for 6 months ARM B and C: 800 mg/mq every 14 days for 6 months
Other intervention name(s): XELODA; cisplatino TEVA; farmorubicina; GEMZAR
Intervention MeSH terms: Gemcitabine; Capecitabine; Epirubicin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adenocarcinoma of the pancreas; stage I pancreatic cancer; stage II pancreatic cancer