The PLATINUM Trial: Optimizing Chemotherapy for the Second-Line Treatment of Metastatic BRCA1/2 or PALB2-Associated Metastatic Pancreatic Cancer

Eligibility Criteria

• * Metastatic pancreatic adenocarcinoma. Adenosquamous carcinoma, squamous carcinoma, acinar cell carcinoma, and carcinoma not otherwise specified are also acceptable
• * BRCA1/2 or PALB2 mutation (somatic or germline) identified on any Clinical Laboratory Improvement Amendments (CLIA)-certified gene panel. Mutations must be considered pathogenic or likely pathogenic by a reference database such as ClinVar or OncoKb.org. (Submission of mutation report will be required)
• * Measurable disease
• * Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment
• * Clinical or radiographic progression on first-line FOLFIRINOX (or nanoliposomal irinotecan, fluorouracil, leucovorin, and oxaliplatin \[NALIRIFOX\]) for metastatic disease
• * Patients whose front-line chemotherapy was required to be simplified due to toxicity associated with any of the constituent components of FOLFIRINOX/NALIRIFOX (e.g. simplified to leucovorin calcium, fluorouracil, and oxaliplatin \[FOLFOX\], leucovorin calcium, fluorouracil, and irinotecan \[FOLFIRI\], fluorouracil \[5-FU\] \[including capecitabine\]) will be eligible
• * Patients with progressive disease while on maintenance PARP inhibitor treatment after FOLFIRINOX (or NALIRIFOX), irrespective of how long ago they received FOLFIRINOX/NALIRIFOX, will also be eligible
• * Patients who develop metastatic disease during or within 6 months after completing FOLFIRINOX/NALIRIFOX in either the locally advanced or adjuvant/neoadjuvant settings will be eligible
• * Patients may not have received prior cisplatin for their pancreatic cancer in any setting
• * Age \>= 18 years
• * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky performance status \>= 60)
• * Absolute neutrophil count \>= 1,500/mm\^3
• * Platelet count \>= 100,000/mm\^3
• * Hemoglobin \>= 8.0 g/dL
• * Creatinine =\< 1.8 x institutional upper limit of normal (ULN) or calculated creatinine clearance (Calc. CrCl) \> 40 mL/min
• * Total bilirubin =\< 2.0 x institutional ULN
• * Aspartate transaminase (AST)/alanine transaminase (ALT) =\< 3 x institutional ULN
• * Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
• * Patients with \> grade 2 peripheral sensory neuropathy are not eligible
• * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• * Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for at least 8-weeks.
• * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load anytime within 6 months prior to registration are eligible for this trial
• * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• * Concomitant chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study
• * Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment
• * N/A