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

Inclusion 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 ClinicalLaboratory Improvement Amendments (CLIA)-certified gene panel. Mutations must beconsidered pathogenic or likely pathogenic by a reference database such as ClinVaror OncoKb.org. (Submission of mutation report will be required)

• Measurable disease

• Potential trial participants should have recovered from clinically significantadverse events of their most recent therapy/intervention prior to enrollment

• Clinical or radiographic progression on first-line FOLFIRINOX (or nanoliposomalirinotecan, fluorouracil, leucovorin, and oxaliplatin [NALIRIFOX]) for metastaticdisease

• Patients whose front-line chemotherapy was required to be simplified due totoxicity associated with any of the constituent components ofFOLFIRINOX/NALIRIFOX (e.g. simplified to leucovorin calcium, fluorouracil, andoxaliplatin [FOLFOX], leucovorin calcium, fluorouracil, and irinotecan [FOLFIRI], fluorouracil [5-FU] [including capecitabine]) will be eligible

• Patients with progressive disease while on maintenance PARP inhibitor treatmentafter FOLFIRINOX (or NALIRIFOX), irrespective of how long ago they receivedFOLFIRINOX/NALIRIFOX, will also be eligible

• Patients who develop metastatic disease during or within 6 months aftercompleting FOLFIRINOX/NALIRIFOX in either the locally advanced oradjuvant/neoadjuvant settings will be eligible

• Patients may not have received prior cisplatin for their pancreatic cancer in anysetting

• Note: Patients may have previously received gemcitabine +/- nab-paclitaxel forresectable (neoadjuvant/adjuvant) or locally advanced disease if (1) treatment wascompleted > 1 year ago and (2) in the opinion of the treating provider, re-treatmentwith gemcitabine/nab-paclitaxel is appropriate

• Age >= 18 years

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofskyperformance 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 calculatedcreatinine clearance (Calc. CrCl) > 40 mL/min

• Total bilirubin =< 2.0 x institutional ULN

• Any elevated bilirubin should be asymptomatic at enrollment (except forparticipants with documented Gilbert's syndrome who may only be included if thetotal bilirubin =< 3 x ULN or direct bilirubin =< 1.5 x ULN)

• Aspartate transaminase (AST)/alanine transaminase (ALT) =< 3 x institutional ULN

• AST/ALT of =< 5 x ULN if liver metastases are present

• Not pregnant and not nursing, because this study involves an agent that has knowngenotoxic, mutagenic and teratogenic effects

• Therefore, for women of childbearing potential only, a negative pregnancy testdone =< 14 days prior to registration is required

• Patients with > grade 2 peripheral sensory neuropathy are not eligible

• Patients with a prior or concurrent malignancy whose natural history or treatmentdoes not have the potential to interfere with the safety or efficacy assessment ofthe investigational regimen are eligible for this trial

• Patients with treated brain metastases are eligible if follow-up brain imaging aftercentral nervous system (CNS)-directed therapy shows no evidence of progression forat least 8-weeks.

• Patients with known, new or progressive brain metastases (active brain metastases)or leptomeningeal disease are ineligible

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviraltherapy with undetectable viral load anytime within 6 months prior to registrationare eligible for this trial

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBVviral load must be undetectable on suppressive therapy, if indicated.

• Patients with a history of hepatitis C virus (HCV) infection must have beentreated and cured. For patients with HCV infection who are currently on treatment,they are eligible if they have an undetectable HCV viral load

• Concomitant chronic concomitant treatment with strong inhibitors of CYP3A4 is notallowed on this study. Patients on strong CYP3A4 inhibitors must discontinue thedrug for 14 days prior to registration on the study

• Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patientsmust discontinue the drug 14 days prior to the start of study treatment

Exclusion Criteria:

• N/A