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
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
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.
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.
Inclusion Criteria:

 -  Patients must have histologically or cytologically proven pancreatic adenocarcinoma;
 histologies other than adenocarcinoma, or any mixed histologies, will NOT be eligible

 -  Patients must have measurable disease in the pancreas; computed tomography (CT) scans
 or magnetic resonance imaging (MRIs) used to assess measurable disease must have been
 completed within 28 days prior to registration; all disease must be assessed and
 documented on the baseline tumor assessment form

 -  Patients must have resectable primary tumor based on contrast-enhanced CT or MRI (CT
 or MRI without contrast as part of positron emission tomography [PET]/CT or PET/MRI is
 NOT acceptable; CT or MRI with contrast as part of PET/CT or PET/MRI is acceptable) of
 the chest, abdomen, and pelvis, where resectable is defined as:

 -  No involvement of the celiac artery, common hepatic artery, and superior
 mesenteric artery (and, if present, replaced right hepatic artery)

 -  No involvement, or < 180° interface between tumor and vessel wall, of the portal
 vein and/or superior mesenteric vein; and patent portal vein/splenic vein
 confluence

 -  No evidence of metastatic disease

 -  Note: for tumors of the body and tail of the pancreas, involvement of the splenic
 artery and vein of any degree is considered resectable disease

 -  CT scans or MRIs used to assess disease at baseline must be submitted for central
 review

 -  Patients must have surgical consult to verify patient is a surgical candidate within
 21 days prior to registration

 -  Patients must not have received prior surgery, radiation therapy, chemotherapy,
 targeted therapy, or any investigational therapy for pancreatic cancer

 -  Patients must have a Zubrod performance status of 0-1

 -  Absolute neutrophil count (ANC) >= 1,500/mcL

 -  Platelets >= 100,000/mcL

 -  Hemoglobin >= 9 g/dL

 -  Total bilirubin =< 1.5 x institutional upper limit of normal (IULN)

 -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x IULN

 -  Serum albumin >= 3 g/dL

 -  Serum creatinine =< IULN within 14 days prior to registration

 -  Patients with uncontrolled intercurrent illness including, but not limited to ongoing
 or active infection, symptomatic congestive heart failure, unstable angina pectoris,
 cardiac arrhythmia, or psychiatric illness/social situations that would limit
 compliance with study requirements will NOT be eligible

 -  No prior malignancy is allowed except for adequately treated basal (or squamous cell)
 skin cancer, in situ cervical cancer, in situ breast (ductal or lobular) cancer, or
 other cancer for which the patient has been disease and treatment-free for two years

 -  Patients must not be pregnant or nursing; women/men of reproductive potential must
 have agreed to use an effective contraceptive method for up to 3 months after the
 final administered dose of chemotherapy; a woman is considered to be of "reproductive
 potential" if she has had menses at any time in the preceding 12 consecutive months;
 in addition to routine contraceptive methods, "effective contraception" also includes
 heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect
 of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or
 bilateral tubal ligation; however, if at any point a previously celibate patient
 chooses to become heterosexually active during the time period for use of
 contraceptive measures, he/she is responsible for beginning contraceptive measures

 -  Sites must seek additional patient consent for the future use of specimens

 -  Patients must be informed of the investigational nature of this study and must sign
 and give written informed consent in accordance with institutional and federal
 guidelines

 -  As a part of the OPEN registration process the treating institution's identity is
 provided in order to ensure that the current (within 365 days) date of institutional
 review board approval for this study has been entered in the system