The main objective of the clinical trial is to determine if modified FOLFIRINOX (mFFX) alternated with biweekly Gemcitabine plus Nab-Paclitaxel (mGnabP) administered as a combined, front-line therapy will result in longer time to treatment failure (TTF) compared to the current standard of care with mFFX alone in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (PDAC).

1. Primary objective:

   To determine whether mFFX and mGnabP administered as a combined, alternating, front-line therapy can provide longer first line treatment for patients with metastatic pancreatic cancer, with the primary metric of time to treatment failure (TTF), including progression of disease (PD), death or treatment discontinuation due to toxicity.

   • Primary endpoint: TTF (treatment discontinuation due to toxicity, disease progression, or death).

2. Secondary objectives:

1) To determine objective response rate (ORR) of the regimen. 2) To determine progression-free survival (PFS) rate of the regimen. 3) To determine overall survival (OS) rate of the regimen. 4) To assess biomarker response (CA-19.9) to the regimen. 5) To examine safety and tolerability of the new regimen. 6) To examine health-related quality of life in patients receiving this regimen.

• Secondary endpoints:

1. ORR as determined by the proportion of subjects with either complete response (CR) or partial response (PR), as defined by RECIST 1.1.
2. PFS as determined by the time interval from the date of first dose of study regimen to first documented PD or death from any cause, whichever occurs first.
3. Overall survival (OS) as defined as the time interval from the date of the first dose of study regimen to date of death from any cause.
4. Biomarker response, measured by serum CA 19-9 levels every 4 weeks.
5. Safety and tolerability of the mFFX alternating with mGnabP regimen; Grade 3 and 4 toxicities will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Follow up for toxicity will be recorded for the first 30 days following the last chemotherapy cycle, and any long-term toxicity will be followed for up to 2 years after completion of study therapy.

3. Exploratory objectives:

1. To determine the tumor molecular profile prior to initiation of chemotherapy and correlate with treatment response.
2. To analyze ct-DNA as a biomarker of response to therapy and early detection of disease progression.

Inclusion Criteria:

1. Histologically and/or cytologically confirmed pancreatic adenocarcinoma.
2. Stage IV disease. The definitive diagnosis of metastatic pancreatic adenocarcinoma will be made by integrating the histopathological data within the context of the clinical and radiographic data.
3. Subject must have received no prior therapy for the treatment of metastatic disease. Prior treatment with 5-FU or gemcitabine administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed. If a subject received prior neoadjuvant or adjuvant chemotherapy, tumor recurrence must have occurred more than 6 months after completing the last dose of chemotherapy.
4. ECOG performance status of 0-1.
5. At least 18 years of age.
6. Evidence of measurable or non-measurable but evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Tumors within a previously irradiated field will be designated as "nontarget" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiotherapy.
7. Female patients of childbearing potential must have a negative pregnancy test (serum or urine) prior to enrollment. Male and female patients must agree to use effective barrier contraception during the period of therapy.
8. Adequate bone marrow function:

8a. ANC ≥ 1500/uL 8b.platelet count ≥ 100,000/uL 8c. hemoglobin ≥ 9.0 g/dL 9. Adequate hepatic function: 9a. Total bilirubin ≤ 1.5 X ULN 9b. AST (SGOT) ≤ 5 X ULN 9c. ALT (SGPT) ≤ 5 X ULN Patients with biliary obstruction must have restored biliary flow by placement of an endoscopic common bile duct stent or a percutaneous drainage.

10. Adequate renal function, Creatinine < 1.5x institutional ULN or calculated creatinine clearance ≥ 50 mL/min as estimated using the Cockcroft-Gault formula.

11. Partial thromboplastin time (PTT) < 1.2 x ULN and INR ≤ 1.5 x ULN, if not receiving anticoagulation therapy. For patients receiving anticoagulants, exceptions to these coagulation parameters are allowed if they are within the intended or expected range for their therapeutic use.

12. Subject must have no clinically significant abnormalities in urinalysis results (obtained ≤ 14 days prior to starting Cycle 1 Day 1).

13. Ability to understand the nature of this study protocol and give written informed consent. 14. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

Patients who meet any one of the following criteria will be excluded from this study.

1. Ineligible histology including non-adenocarcinomas, adenosquamous carcinoma, islet cell carcinomas, cystadenomas, cystadenocarcinomas, carcinoid tumors, duodenal carcinomas, distal bile duct and ampullary carcinomas.
2. Any condition including the presence of laboratory abnormalities, which, in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study.
3. Presence of central nervous system metastases.
4. Life expectancy < 12 weeks.
5. Pregnancy (positive pregnancy test) or lactation.
6. Pre-existing sensory neuropathy > grade 1.
7. Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 6 months.
8. Major surgery without complete recovery in the past 4 weeks prior to screening.
9. Prior malignancy except for adequately treated basal cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other form of cancer from which the patient has been disease-free for 5 years.
10. Concurrent active infection.
11. Patient with uncontrolled and/ or active infection with HIV, Hepatitis B or Hepatitis C.
12. Patient who has a history of allergy or hypersensitivity to any of the study drugs.
13. Patients with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, interstitial pulmonary fibrosis, pulmonary hypersensitivity pneumonitis.
14. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.