This is a research study to evaluate how the genetic makeup of Pancreatic Ductal Adenocarcinoma (PDAC) can affect the response to FDA-approved chemotherapy treatment, FOLFIRINOX, given before surgery to remove the tumor. Certain types of PDAC tumors can be surgically resected (removed). However, not all types of PDACs are resectable, especially if they are close to important structures like blood vessels or intestines. These types of PDACs are treated with chemotherapy such as FOLFIRINOX. Research studies showed that chemotherapy after surgical resection of PDAC tumors reduced the risk of the cancer returning.
Chemotherapy is used to treat PDAC that has not spread outside of the pancreas and is not resectable. FOLFIRINOX is a chemotherapy treatment that combines multiple chemotherapeutic agents, including oxaliplatin, leucovorin, irinotecan, and 5-FU. Patients receive these agents by intravenous infusion. Of these drugs, 5-FU requires you to return home with a chemotherapy pump that will deliver chemotherapy over 46 hours. This regimen has been studied in pancreatic cancer that has been removed with surgery as a method for preventing the cancer from returning. Studies showed FOLFIRINOX chemotherapy reduced the risk of cancer returning and increased patients survival. In this study, researchers want to know if FOLFIRINOX chemotherapy given before surgery will make the cancer easier to remove with surgery and increase the chances of the cancer staying away after surgery.
Researchers have shown that pancreatic cancers are not all the same when you look at the DNA and RNA that is inside a pancreatic cancer cell.
Depending on the expression of different genes in a cancer cell, some pancreatic cancers may respond differently to chemotherapy. In this study researchers want to know if FOLFIRINOX chemotherapy can change the genetic profile of the cancer. This will be studied by obtaining a biopsy of the cancer before the start of chemotherapy, and after 8 treatments of chemotherapy. They will also study cancer cells that will be collected from blood samples.
Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
Histologically or cytologically confirmed adenocarcinoma of the pancreas with no evidence of distant metastatic disease.
Subject has no evidence of co-morbidities precluding the potential to undergo surgical resection of PDAC as determined by surgical investigator.
Subjects must be willing to undergo a mandatory pre- and post-treatment EUS guided core biopsy of the pancreatic mass.
Subject has any evidence of local recurrence or metastatic pancreatic cancer.
Other malignancies within the past 5 years except for adequately treated cervical or vulvar carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis and T1).
Subject has hypersensitivity to 5FU, oxaliplatin or other platinum agent, or irinotecan or to their excipients.
Subject has known dihydropyrimidine dehydrogenase (DPD) enzyme deficiency.
Single group
Oxaliplatin
Drug85 mg/m2 in 250 cc Dextrose solution given by IV on Day 1 of each 14-day cycle
Leucovorin
Drug400 mg/m2 in 100 cc dextrose solution given with irinotecan by IV on Day 1 of each 14-day cycle
Irinotecan Hydrochloride
Drug180 mg/m2 in 500cc dextrose solution given with leucovorin by IV on Day 1 of each 14-day cycle
5-FU
Drug400 mg/m2 bolus and then 2400 mg/m2 via continuous infusion on Day 1 of each 14-day cycle
Best disease control rate by Pancreatic ductal adenocarcinoma (PDAC) subtype
To evaluate the association between PDAC tumor subtype (particularly basal-like versus classical subtype) and best disease control rate (DCR) after administration of FOLFIRINOX in subjects with non-metastatic pancreatic cancer, DCR is defined as the proportion of patients with either Complete Response (CR), partial response (PR), or stable disease (SD) as determined by RECIST 1.1, Response Evaluation Criteria In Solid Tumors Criteria. CR is defined as disappearance of all target lesions; PR as a \>=30% decrease in the sum of the longest diameter of target lesions; and SD as no response or less response than Partial or Progressive.
Rate of resectability
The number of patients who following treatment with FOLFIRINOX were subsequently deemed to have resectable disease and underwent surgical resection
Overall survival
median overall survival (OS) of all patients receiving FOLFIRINOX on study as well as in 1) resectable, 2) borderline resectable and 3) unresectable PDAC, measured from the start of treatment until death from any cause.
Progression free survival
Median time from start of treatment until death or progression as defined by RECIST 1.1 Criteria, for all patients and with respect to each tumor and stroma subtype. Progressive Disease (PD), is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
best objective response rate (ORR; complete response (CR) + partial response (PR))
Estimation of the best ORR for all patients and with respect to each tumor and stroma subtype. ORR is defined as the proportion of patients with either Complete Response (CR) or partial response (PR) as determined by RECIST 1.1, Response Evaluation Criteria In Solid Tumors Criteria. CR is defined as disappearance of all target lesions; PR as a \>=30% decrease in the sum of the longest diameter of target lesions;
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