Trial to Investigate Intensified Neoadjuvant Chemotherapy in Locally Advanced Pancreatic Cancer
Condition: Ductal Adenocarcinoma of the Pancreas
Study type: Interventional
Phase: Phase 2

Summary: 
      The aim ot the study is to investigate the efficacy and safety of two new intensified
      chemotherapy regimens (gemcitabine (Gem)/nab- paclitaxel (PAC), FOLFIRINOX) as neoadjuvant
      chemotherapy protocol in locally advanced, non-metastatic pancreatic cancer (LAPC) and
      consecutive conversion of the tumor to resectability.
    

Detailed description: 
      This is a prospective open randomized multicenter phase II trial with two arms.

      Patients suffering from histologically confirmed LAPC (and assessed as unresectable or
      borderline resectable according to National Comprehensive Cancer Network (NCCN) Clinical
      Practice Guidelines "pancreatic adenocarcinoma" version 1.2013) without metastases will
      receive two different neoadjuvant treatment regimens:

      First all patients receive two cycles Gem/nab-PAC (duration of each cycle 28 days) as
      neoadjuvant chemotherapy in equal measure and a first restaging is performed after these two
      cycles based on imaging criteria. If there is no progression according to Response evaluation
      criteria in solid tumors (RECIST 1.1) criteria at the first restaging, the patients are
      randomized in a 1:1 relation to:

      Two further cycles Gem/nab-PAC (duration of each cycle 28 days). or Four further cycles
      FOLFIRINOX (duration of each cycle 14 days). After the neoadjuvant chemotherapy a 2nd
      restaging is performed based on imaging criteria. All patients without progression at this
      restaging or at an earlier time point undergo obligatory exploratory laparotomy irrespective
      of imaging criteria to assess resectability. If they are evaluated as converted to resectable
      during this exploratory laparotomy, pancreas resection in curative intent will be performed.
      All patients with successful R0 or R1 pancreatic resection will receive three further cycles
      adjuvant chemotherapy with Gem/nab-PAC. Adjuvant chemotherapy will start within 4 to 8 weeks
      after pancreatic resection surgery.

      Further treatment of patients with PD after 1st or 2nd restaging as well as patients with
      unresectable status based on exploratory laparotomy is under the discretion of the local
      investigators (e.g. second-line chemotherapy in case of distant relapse or local
      radiochemotherapy in case of local progression or definitive irresectability).

      All patients are followed up for local recurrence, progression and survival until death or
      for at least one year after last application of study drugs whichever is sooner.

      The translational research conducts exploratory analyses for potential biomarkers of possible
      prognostic or predictive value for efficacy of neoadjuvant chemotherapy in LAPC; including
      analyses of circulating tumor cells, molecular pathways of pancreatic adenocarcinoma
      including SPARC expression.
    

Intervention name(s): Gem/nab-Pac; FOLFIFINOX
Intervention type(s): Drug; Drug
Intervention description(s): All patient receive:
2 cycles gemcitabine/nab-paclitaxel ([Gem/nab-Pac]; duration of each cycle 28 days)
Then:
Nab-paclitaxel 125 mg/m2, IV infusion over 30 minutes, followed by gemcitabine 1000 mg/m2 as a 30-minute IV infusion on D1, D8, D15 of each 28-day cycle; All patient receive:
2 cycles gemcitabine/nab-paclitaxel ([Gem/nab-Pac]; duration of each cycle 28 days)
Then:
Oxaliplatin 85 mg/m2, given as a 2-hour intravenous infusion D1 Folinic acid 400 mg/m2, given as a 2-hour intravenous infusion D1 Irinotecan 180 mg/m2, given as a 90-minutes intravenous infusion D1 (application through a Y-connector parallel to infusion of folinic acid or 30 minutes after start of folinic acid possible) Fluorouracil 400 mg/m2, administered by intravenous bolus, followed by a continuous intravenous infusion of fluorouracil 2400 mg/m2 over a 46-hour period D1.
To be repeated on D1 of each cycle.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: unresectable; borderline resectable