Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Gemcitabine Hydrochloride With or Without WEE1 Inhibitor AZD1775 in Treating Patients With Previously Untreated Pancreatic Cancer That Is Metastatic or Cannot Be Removed by Surgery

Inclusion Criteria (Phase I):

• Patients must have histologically or cytologically confirmed metastatic or unresectable locally advanced adenocarcinoma of the pancreas. Prior therapy with a non-gemcitabine based regimen is permitted.
• Previous neo-adjuvant or adjuvant treatment is allowed provided that it was given >= 6 months prior to registration
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Patients must have a life expectancy of >= 12 weeks
• Patients may have had prior radiotherapy for metastatic disease as long as it was > 4 weeks prior to registration and the patient has recovered from adverse events associated with the radiotherapy
• Patients must be able to swallow capsules whole
• Patients must be able to tolerate computed tomography (CT), magnetic resonance imaging (MRI) or PET imaging including contrast agents
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal and barrier method of birth control; two barrier methods of birth control; abstinence) for the duration of study treatment and for 3 months after the last dose of study treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; should a man impregnate or suspect that he has impregnated a woman while participating in this study, he should inform his treating physician immediately
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Hemoglobin >= 9 g/dL
• Platelets >= 100,000/mcL
• Total bilirubin = = 60 mL/min for patients with creatinine levels above institutional upper limit of normal (ULN)

Exclusion Criteria (Phase I):

• Receiving any other investigational agents concurrently
• Have received any other investigational agents = grade 1 motor or sensory neuropathy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nab-paclitaxel, gemcitabine or AZD1775
• Major surgical procedures 5 years
• Pregnant or breast-feeding
• Females of childbearing potential must have a blood test or urine study within 5 days prior to registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• At least18 years of age

Inclusion Criteria (Phase II):

• Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas
• Patients must have measurable disease outside of the primary tumor (pancreas) by RECIST 1.1 criteria; baseline measurements and evaluations of all sites of disease must be obtained = 4 weeks prior to randomization and the patient has recovered from adverse events associated with the radiotherapy
• ECOG performance status of 0 or 1
• Life expectancy of >= 12 weeks
• Patients must be able to swallow capsules whole
• Patients with biliary stents are allowed
• Patients must be able to tolerate CT, MRI or PET imaging including contrast agents
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal and barrier method of birth control; two barrier methods of birth control; abstinence) for the duration of study treatment and for 3 months after the last dose of study treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; should a man impregnate or suspect that he has impregnated a woman while participating in this study, he should inform his treating physician immediately
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Hemoglobin >= 9 g/dL
• Platelets >= 100,000/mcL
• Total bilirubin = = 60 mL/min for patients wi