Biologically Optimized Infusion Schedule of Gemcitabine and Nab-Paclitaxel for the Treatment of Metastatic Pancreatic Cancer

Inclusion Criteria:

• Participant has definitive histologically or cytologically confirmed adenocarcinomaof the pancreas. The definitive diagnosis of metastatic pancreatic adenocarcinomawill be made by integrating the histopathological data within the context of theclinical and radiographic data. Participants with islet cell neoplasms are excluded

• Patient has one or more metastatic tumors measurable by computed tomography (CT)scan (or magnetic resonance imaging [MRI], if patient is allergic to CT contrastmedia or if the tumor is difficult to delineate on CT scan) as defined by RECIST 1.1criteria

• Non-pregnant and non-lactating

• If a female patient is of child-bearing potential, as evidenced by regularmenstrual periods, she must have a negative serum pregnancy test beta-humanchorionic gonadotropin (beta-hCG) documented 72 hours prior to the firstadministration of study drug

• The patient must agree to use a method of contraception considered highlyeffective by the investigator during the period of administration of study drugand after the end of treatment for an additional 3 months. Adequate birthcontrol methods are defined below

• Women will be considered of childbearing potential unless surgicallysterilized by hysterectomy or bilateral tubal ligation/salpingectomy, orif they are post-menopausal (defined as absence of menses for at least 1year). Sexually active men and women of childbearing potential who aresexually active and not willing to use a highly effective method of birthcontrol during the trial and for at least three months after will beconsidered ineligible for the trial. A highly effective method of birthcontrol is defined as one which results in a low failure rate (i.e. lessthan 1% per year) when used consistently and correctly, such as implants,injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomized partner. In the event that localregulations require additional restrictions to the above definition, thepatient information will specify the acceptable contraceptive methods

• Patients must have received no previous chemotherapy or investigational therapy forthe treatment of metastatic pancreatic cancer. Prior adjuvant treatment is allowedas long as the last chemotherapy was > 6 months ago. Prior use of 5-fluorouracil (5-FU) or gemcitabine administered as a radiation sensitizer or in the adjuvantsetting is allowed, provided at least 2 month have elapsed since completion of thelast dose and no lingering significant toxicities are present. Prior radiation isallowed as long as the planned lesion(s) to be measured were not previously radiated

• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (obtained =< 14 days prior torandomization)

• Platelet count >= 100,000/mm^3 (100 x 10^9/L) (obtained =< 14 days prior torandomization)

• Hemoglobin (Hgb) >= 9 g/dL (obtained =< 14 days prior to randomization)

• Aspartate transaminase (AST), serum glutamic-oxaloacetic transaminase (SGOT),alanine transaminase (ALT) serum glutamic-pyruvic transaminase (SGPT) =< 2.5 x upperlimit of normal range (ULN), unless liver metastases are clearly present, then =< 5x ULN is allowed (obtained =< 14 days prior to randomization)

• Total bilirubin =< 2 x ULN (obtained =< 14 days prior to randomization)

• Patient has Karnofsky performance status (KPS) >= 60 or Eastern Cooperative OncologyGroup (ECOG) performance status of 0-2

• Patient has been informed about the nature of the study, has agreed to participatein the study, and signed the informed consent form (ICF) prior to participation inany study-related activities

Exclusion Criteria:

• Patient has known brain metastases, unless previously treated and well-controlledfor at least 3 months (defined as clinically stable, no edema, no steroids andstable in 2 scans at least 4 weeks apart)

• Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiringsystemic therapy

• Patient has known active infection with human immunodeficiency virus (HIV),hepatitis B, or hepatitis C. HIV-infected patients on effective anti-retroviraltherapy with undetectable viral load within 6 months are eligible for this trial

• Patient has a history of allergy or hypersensitivity to any of the study drugs orany of their excipients

• Patient has serious medical risk factors involving any of the major organ systems,or serious psychiatric disorders, which could compromise the patient's safety or thestudy data integrity based on the assessment of the enrolling physician

• Patient is unwilling or unable to comply with study procedures