Liposomal Irinotecan, Fluorouracil, Leucovorin Calcium, and Rucaparib in Treating Patients With Metastatic Pancreatic, Colorectal, Gastroesophageal, or Biliary Cancer

Inclusion Criteria

• •Phase I only: Histologic confirmation of pancreatic, colorectal, gastroesophageal or biliary adenocarcinoma, as follows:
• •* Patients with metastatic disease from pancreatic cancer who received no more than 2 lines of prior therapy in the metastatic setting
• •* Patients with metastatic disease from colorectal cancer who received no more than 3 lines of prior therapy in the metastatic setting
• •* Patients with metastatic disease from gastroesophageal cancer who received no more than 1 line of prior therapy in the metastatic setting
• •* Patients with metastatic disease from biliary tract cancer who received no more than 1 line of prior therapy in the metastatic setting
• •* NOTE: No prior exposure to irinotecan in the metastatic setting will be allowed except in the phase I dose escalation portion and in colon cancer patients only; in pancreas cancer, exposure to irinotecan is only allowed in the neoadjuvant setting and no progressive disease \< 3 months from last dose of irinotecan
• •Phase Ib only: Patients with metastatic adenocarcinoma of the pancreas who have who received no more than 1 line of prior therapy in the metastatic setting
• •* NOTE: Exposure to irinotecan is only allowed in the neoadjuvant setting and no progressive disease \< 3 months from last dose of irinotecan
• •Phase II only: Patients with metastatic adenocarcinoma of the pancreas with genomic markers (signature) of homologous recombination deficiency (HRD) or BRCA1 or BRCA2 or PALB2 mutation, or HRD (non-BRCA, non-PALB) who have not received any systemic therapy in the metastatic setting
• •* NOTE: Exposure to irinotecan is only allowed in the neoadjuvant setting and no progressive disease \< 3 months from last dose of irinotecan
• •Measurable disease
• •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• •Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 21 days prior to registration)
• •Platelet count \>= 100,000/mm\^3 (obtained =\< 21 days prior to registration)
• •Hemoglobin \> 9.0 g/dL (obtained =\< 21 days prior to registration)
• •Total bilirubin =\< institutional upper limit of normal (ULN) (obtained =\< 21 days prior to registration)
• •Aspartate transaminase (AST) =\< 3 x ULN, =\< 5.0 x ULN for patients with metastatic disease to the liver (obtained =\< 21 days prior to registration)
• •Aminotransferase (ALT) =\< 3.0 x ULN, =\< 5.0 x ULN for patients with metastatic disease to the liver (obtained =\< 21 days prior to registration)
• •Creatinine =\< 1.0 mg/dL or creatinine clearance \>= 45 ml/min using the Cockcroft-Gault formula (obtained =\< 21 days prior to registration)
• •Negative serum or urine pregnancy test done =\< 7 days prior to registration and repeated prior to dosing on day 1 of each cycle, for individuals of childbearing potential only; NOTE: Individuals are considered to be of childbearing potential unless one of the following applies:
• •* Is postmenopausal, defined as no menses for at least 12 months without an alternative medical cause; a high follicle-stimulating hormone (FSH) level consistently in the postmenopausal range (30 mIU/mL or higher) may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to confirm a postmenopausal state: or
• •* Considered to be permanently sterile; permanent sterilization includes hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy
• •Provide informed written consent
• •Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
• •* Note: During the active monitoring phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
• •Willing to provide tissue and blood samples for mandatory correlative research purposes
• •Individuals of reproductive potential and their partners willing to practice total abstinence or use a highly effective method of contraception (failure rate \< 1% per year) during treatment and for 6 months following the last dose of rucaparib; the following are allowable only:
• •* Ongoing use of progesterone-only injectable or implantable contraceptives (eg, Depo Provera, Implanon, Nexplanon)
• •* Placement of an intrauterine device or intrauterine system
• •* Bilateral tubal occlusion
• •* Sterilization, with appropriate post-vasectomy documentation of absence of sperm in ejaculate
• •* True, complete (as opposed to periodic) abstinence
• •Patients must discontinue prior chemotherapy \>= 28 days before registration