S1505: Combination Chemotherapy or Gemcitabine Hydrochloride and Paclitaxel Albumin-Stabilized Nanoparticle Formulation Before Surgery in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery
Condition: Pancreatic Adenocarcinoma; Resectable Pancreatic Carcinoma
MeSH terms: Adenocarcinoma; Pancreatic Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      This randomized phase II trial studies how well fluorouracil, irinotecan hydrochloride, and
      oxaliplatin (combination chemotherapy) works and compares to gemcitabine hydrochloride and
      paclitaxel albumin-stabilized nanoparticle formulation before surgery in treating patients
      with pancreatic cancer that can be removed by surgery. Drugs used in chemotherapy, such as
      fluorouracil, irinotecan hydrochloride, oxaliplatin, gemcitabine hydrochloride, and
      paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the
      growth of tumor cells, either by killing the cells, by stopping them from dividing, or by
      stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill
      more tumor cells. It is not yet known whether combination chemotherapy is more effective than
      gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation before
      surgery in treating pancreatic cancer.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To assess 2-year overall survival in each treatment arm (fluorouracil, irinotecan
      hydrochloride, and oxaliplatin [modified (m)FOLFIRINOX] and gemcitabine [gemcitabine
      hydrochloride]/nab-paclitaxel [paclitaxel albumin-stabilized nanoparticle formulation]) in
      patients with resectable pancreatic cancer.

      II. If the stated threshold is met in one or both arms: to choose the better regimen with
      respect to 2-year overall survival.

      SECONDARY OBJECTIVES:

      I. To estimate, for all patients and within treatment arms: frequency and severity of adverse
      events associated with chemotherapy in the perioperative setting.

      II. To estimate, for all patients and within treatment arms: proportion of patients going to
      surgery for resection after preoperative chemotherapy.

      III. To estimate, for all patients and within treatment arms: proportion of patients
      achieving macroscopically complete tumor removal with negative microscopic surgical margins
      (R0) resection after preoperative chemotherapy.

      IV. To estimate, for all patients and within treatment arms: overall response rate following
      preoperative chemotherapy, including confirmed and unconfirmed, complete and partial
      response, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

      V. To estimate, for all patients and within treatment arms: pathologic response rates after
      R0 or macroscopically complete tumor removal with any positive microscopic surgical margin
      (R1) resection.

      VI. To estimate, for all patients and within treatment arms: patterns of recurrence
      (loco-regional, distant) after R0 or R1 resection.

      VII. To estimate, for all patients and within treatment arms: disease-free survival from the
      time of R0 or R1 resection.

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

      ARM I: Patients receive oxaliplatin intravenously (IV) over 2 hours and irinotecan
      hydrochloride IV over 90 minutes on days 1 and 15. Patients also receive fluorouracil IV over
      46 hours on days 1-3 and 15-17. Treatment repeats every 28 days for 3 courses in the absence
      of disease progression or unacceptable toxicity. Patients achieving stable disease or better
      undergo pancreatectomy 4-8 weeks after completion of first 3 courses of treatment. Within 4-8
      weeks following pancreatectomy, patients receive an additional 3 courses of oxaliplatin,
      irinotecan hydrochloride, and fluorouracil treatment in the absence of disease progression or
      unacceptable toxicity.

      ARM II: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30
      minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment
      repeats every 28 days for 3 courses in the absence of disease progression or unacceptable
      toxicity. Patients achieving stable disease or better undergo pancreatectomy 4-8 weeks after
      completion of first 3 courses of treatment. Within 4-8 weeks following pancreatectomy,
      patients receive an additional 3 courses of paclitaxel albumin-stabilized nanoparticle
      formulation and gemcitabine hydrochloride treatment in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 2 years and
      then every 6 months for 2 years.
    

Intervention name(s): Fluorouracil; Gemcitabine Hydrochloride; Irinotecan Hydrochloride; Oxaliplatin; Paclitaxel Albumin-Stabilized Nanoparticle Formulation; Pancreatectomy
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Procedure
Intervention description(s): Given IV; Given IV; Given IV; Given IV; Given IV; Undergo pancreatectomy
Other intervention name(s): 5-Fluoro-2,4(1H, 3H)-pyrimidinedione; 5-Fluorouracil; 5-Fluracil; 5-FU; AccuSite; Carac; Fluoro Uracil; Fluouracil; Flurablastin; Fluracedyl; Fluracil; Fluril; Fluroblastin; Ribofluor; Ro 2-9757; Ro-2-9757; dFdCyd; Difluorodeoxycytidine Hydrochloride; Gemzar; LY-188011; Campto; Camptosar; Camptothecin 11; Camptothecin-11; CPT 11; CPT-11; Irinomedac; U-101440E; 1-OHP; Ai Heng; Aiheng; Dacotin; Dacplat; Diaminocyclohexane Oxalatoplatinum; Eloxatin; Eloxatine; JM-83; Oxalatoplatin; Oxalatoplatinum; RP 54780; RP-54780; SR-96669; ABI 007; ABI-007; Abraxane; Albumin-bound Paclitaxel; Albumin-Stabilized Nanoparticle Paclitaxel; nab-paclitaxel; Nanoparticle Albumin-bound Paclitaxel; Nanoparticle Paclitaxel; protein-bound paclitaxel; Excision of the Pancreas; Pancreas Excision
Intervention MeSH terms: Paclitaxel; Camptothecin; Albumin-Bound Paclitaxel; Gemcitabine; Fluorouracil; Oxaliplatin; Irinotecan; Pancrelipase; Pancreatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment