Phase II Study of Hypofractionated Radio-chemotherapy With Gemcitabine Plus Oxaliplatin for Unresectable Nonmetastatic Locally Advanced Pancreatic Cancer.
Condition: Unresectable Pancreatic Cancer; Nonmetastatic Pancreatic Cancer; Locally Advanced Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      Title: Phase II study of hypofractionated radio-chemotherapy with gemcitabine plus
      oxaliplatin for unresectable nonmetastatic locally advanced pancreatic cancer.

      Protocol code: IRST157.01

      Phase: II

      Study Design: monocentric, prospective, open-label not randomized trial.

      Description of Study Treatment: radio-chemotherapy schedule

        -  GEMOX: Gemcitabine (GEM) 1000 mg/m2, day 1, and Oxaliplatin (OX) 100 mg/m2, day 2, every
           2 weeks for 4 cycles.

        -  Hypofractionated radiotherapy (35 Gy in 7 fractions in 9 consecutive days, one session
           per day excluding Saturday and Sunday) administered 15 days after the 4th chemotherapy
           cycle.

        -  Further 4 cycles of GEMOX, starting 7-15 days after the end of the radiotherapy.

      Objectives:

      Step A: primary objective = to evaluate the safety of radiotherapy treatment. Secondary
      objective = the control of IM (internal margin) intra-fraction.

      Step B: primary objective = to evaluate the proportion of the resectable patients after
      radio-chemotherapy. Secondary objectives = overall Response Rate (ORR); safety profile of
      combinated treatment;overall survival (OS); local progression free survival (LPFS) and
      progression free survival (PFS).

      Statistical Considerations:

      Step A:

      Assuming that the probability to observe a toxicity involving the radiotherapy treatment
      discontinuation with the new treatment is less than 20%, 11 patients are to be evaluated for
      toxicity. If no toxicity involving the radiotherapy treatment discontinuation will be
      observed in 11 patients, the treatment can be considered safe with a probability > 90%. If 1
      toxicity involving the radiotherapy treatment discontinuation will be observed, 7 more
      patients needs to be recruited. If no further toxicity involving the radiotherapy treatment
      discontinuation occurs, the treatment could be considered safe with a probability ≥ 90%.

      If 2 or more toxicity involving the radiotherapy treatment discontinuation on 11 patients or
      2 or more toxicity involving the radiotherapy treatment discontinuation on 18 patients will
      be observed, the study will be stopped because not safe and another kind of radiotherapy
      schedule must be designed.

      Step B:

      If the radiotherapy treatment will be considered no toxic, the study will continue in Step B
      : the goal of this phase II study is to increase the proportion of resectable patients of at
      least 15% with the new radio-chemotherapeutic treatment. By using the single-stage design
      (Gehan EA, J Chron Dis 1961) a total of 40 patients is required to be recruited in 2 years,
      and a further one-year period of follow-up is requested. If at least 7 patients out of 40
      enrolled will be resectable, the hypothesis that the proportion of resectable patients will
      be less or equal to P1 (P1=the proportion of resectable patients with the new
      radio-chemotherapeutic treatment) will be refused and the treatment could be considered
      active.
    


Intervention name(s): Gemcitabine; Oxaliplatin; Hypofractionated RT
Intervention type(s): Drug; Drug; Radiation
Intervention description(s): Gemcitabine 1000 mg/m2; Oxaliplatin 100 mg/m2; Hypofractionated radiotherapy (35 Gy in 7 fractions)
Other intervention name(s): oxalipaltin
Intervention MeSH terms: Gemcitabine; Oxaliplatin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment