Utility of ctDNA in Early Switch of First-line mFOLFIRINOX in Metastatic Pancreatic Ductal Adenocarcinoma

Inclusion criteria

• Histologically confirmed, metastatic pancreatic adenocarcinoma. Patients with adenosquamous carcinoma and mixed adenocarcinoma/neuroendocrine carcinoma (MANEC) of the pancreas are eligible, but pure neuroendocrine neoplasms are excluded.
• Treatment-naïve patients diagnosed with metastatic pancreatic adenocarcinoma.
• Must have a detectable circulating tumor deoxyribonucleic acid (DNA) at cycle 1 day 1.
• Patients must have a detectable circulating tumor deoxyribonucleic acid (ctDNA) quantity on Northstar Response assay at baseline.
• At least one tumor measurable by Computed Tomography (CT) scan or Positron Emission Tomography-Computed Tomography (PET/CT) scan. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >20 mm with conventional techniques or >10 mm with spiral CT scan.
• Adult male and female participants (≥ 18 years of age).
• Male or non-pregnant and non-lactating female. Men and women with intact reproductive potential must agree to use contraception.
• Adequate biological parameters as demonstrated by the following blood counts at Screening (obtained ≤ 21 days prior to enrollment) and at Baseline-Day 0:

• Absolute neutrophil count (ANC) ≥ 1.0 × 109 cells/L.
• Platelet count ≥ 100,000 cells/mm3 (100 × 109 cells/L). Supportive platelet transfusions are acceptable.
• Hemoglobin (Hgb) ≥ 9 g/dL. Supportive packed red blood cell transfusions are acceptable.
• Adequate blood chemistry levels at Screening (obtained ≤ 21 days prior to enrollment) and at Baseline-Day 0:

• Aspartate aminotransferase (AST) - serum glutamic-oxaloacetic transaminase (SGOT); alanine transaminase (ALT) - serum glutamic-pyruvic transaminase (SGPT) ≤ 2.5 × upper limit of normal (ULN) range, unless liver metastases are present, then ≤ 5 × ULN is allowed.
• Total bilirubin ≤ 1.5 × Upper Limit of Normal.
• Estimated creatinine clearance of > 60 mL/min (per Cockcroft-Gault formula).
• Albumin ≥ 3.0 g/dL.
• Eastern Cooperative Oncology Group (ECOG) performance status from 0 to ≤ 1.
• Must be a modified Folfirinox chemotherapy candidate.
• For participants not qualified or able to give legal consent, consent must be obtained from their legally authorized representative (LAR).

Exclusion criteria

• Patients with pure neuroendocrine neoplasms of the pancreas.
• Brain metastases.
• Uncontrolled ascites.
• Increase of ECOG to > 1 between screening and enrollment.
• Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
• History of untreated or uncontrolled HIV and/or Hepatitis B or C infection.
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:

• History of myocardial infarction, angina pectoris, symptomatic pericarditis, or coronary artery bypass graft within six months prior to study entry
• Documented cardiomyopathy
• Grade 2 or greater sensory peripheral neuropathy.
• History of chronic diarrhea.
• Pregnant or nursing.
• Concomitant serious medical or psychiatric illness that, in the opinion of the investigator, could compromise the patient's safety or integrity of the study data.
• Concurrently enrolled in any other interventional clinical protocol or investigational trial involving administration of antineoplastic compounds for the treatment of metastatic pancreatic cancer.
• Patient is unwilling or unable to comply with study procedures.
• Patients with impaired decision-making capacity.
• No other medical condition or reason that, in the opinion of the investigator, would preclude study participation.