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

• •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 =\< 1.5 institutional upper limit of normal (ULN)
• •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 X institutional upper limit of normal (ULN) or =\< 5 X ULN if the patient has liver metastases
• •Creatinine =\< 1.5 mg/dL or creatinine clearance (Cockcroft-Gault) \>= 60 mL/min for patients with creatinine levels above institutional upper limit of normal (ULN)
• •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
• •Previous neo-adjuvant or adjuvant treatment is allowed provided that there was no evidence of recurrent disease for at least 6 months after completion of neo-adjuvant/adjuvant treatment
• •Patients may have had prior radiotherapy for metastatic disease as long as it was \> 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 =\< 1.5 institutional upper limit of normal (ULN)
• •AST (SGOT)/ALT (SGPT) =\< 3 X institutional upper limit of normal (ULN) or =\< 5 X ULN if the patient has liver metastases
• •Creatinine =\< 1.5 mg/dL or creatinine clearance (Cockcroft-Gault) \>= 60 mL/min for patients with creatinine levels above institutional upper limit of normal (ULN)
• •For participation in the imaging research studies, patients must meet the additional following criteria:
• •* The patient is participating in the trial at an institutional which has agreed to perform the imaging research studies, completed the American College of Radiation Imaging Network (ACRIN) defined scanner qualification procedures and received ACRIN approval
• •* The patient has consented in writing to participate in one of the imaging research studies
• •* The patient meets the criteria required for the imaging study in which the site is participating:
• •* NOTE: Eligibility for participating in either imaging sub-study will depend on the availability of the imaging sub-study at a particular institution
• •* For participation in the FDG-PET sub-study:
• •* Patients must have an evaluable lesion of \> 20 mm in size on standard practice imaging study as assessed by site (either primary pancreas mass or metastasis)
• •* For participation in the FLT-PET sub-study:
• •* Patients must be able to lie still for a 1.5 hour PET scan.
• •* Patients must have an evaluable lesion in the pancreas \> 20 mm in size on standard practice imaging study as assessed by site (lesion must be likely primary adenocarcinoma of the pancreas that is not primarily fibrotic or mucinous in nature)