Phase I/II Study of Neoadjuvant mFOLFIRINOX in Combination With Peri-operative Oral Hydroxychloroquine (FHQ) in Subjects With Resectable Adenocarcinoma of the Pancreas.
West Virginia University
Summary
This will be a phase I/II trial examining the safety and tolerability of pre-operative mFOLFIRINOX in combination with peri-operative oral hydroxychloroquine (FHQ) in the treatment of subjects with adenocarcinoma of the pancreas. Subjects will be staged prior to protocol entry by contrast-enhanced helical abdominal CT scan done using a pancreas mass protocol or EUS. Eligible subjects with biopsy-proven, resectable pancreatic adenocarcinoma without evidence of venous or arterial involvement on CT scan receive HCQ orally in combination with mFOLFIRINOX prior to surgery. Hydroxychloroquine will begin with the first dose of mFOLFIRINOX and continue for 2 weeks post-operatively. Three to six weeks after the last dose of mFOLFIRINOX, patients will undergo surgical exploration and pancreatectomy if technically feasible and all toxicities have resolved. Pathologic specimens will undergo detailed histopathologic and immunohistochemical evaluations with particular attention to the six surgical margins of resection: the bile duct margin (for Whipple specimens), the margin of pancreatic transection, the retroperitoneal margin, the proximal and distal duodenal margins (for Whipple specimens), and the portal vein margin along the pancreatic head (for Whipple specimens) or medial pancreas (for distal pancreatectomies). Tissue specimens will be stored at -80C for future correlative studies of autophagy and tumor response to protocol therapy. Ten to fourteen weeks following completion of successful surgical removal of their tumor, subjects will undergo repeat staging studies per standard of care. Subjects will pursue standard of care adjuvant therapy options at the discretion of their physician.
Description
A subject is deemed evaluable if they have received at least 3 of 4 cycles of chemotherapy and at least 80% of the expected HCQ doses and undergo successful surgical extirpation their disease. Patients will receive daily oral HCQ concurrently with neoadjuvant mFOLFIRINOX, planned for 4 cycles. Each cycle of mFOLFIRINOX is 14 days, therefore 4 cycles will occur over a period of 56 days. Oral HCQ will continue after completion of neoadjuvant chemotherapy and extend 2 weeks post-operatively. Patients will undergo restaging scans after completion of 4 cycles of mFOLFIRINOX. Within 3 to 6 weeks aft…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria * Subjects with biopsy-proven adenocarcinoma of the pancreas * Pancreatic protocol helical CT scan demonstrating absence of venous or arterial involvement, consistent with NCCN guidelines for resectable disease * ECOG performance status ≤ 1 * No active second malignancy except for basal cell carcinoma of the skin * Normal renal, hepatic, and hematologic function at the time of enrollment as evidenced by: * Serum creatinine level ≤1.5 the upper limits of normal * Serum total bilirubin level ≤1.5 X ULN * White blood cell count ≥ 3.5x109/ml per ml and platelet count ≥ 100…
Interventions
- DrugHydroxychloroquine sulfate
Hydroxychloroquine, oral, dose escalated (400mg, 800mg, 1200mg) beginning concurrent with mFOLFIRINOX and extending 2 weeks post-operatively. Dose will be assigned to patients using 3+3 Algorithm to identify the Maximum Dose Tolerated.
Location
- West Virginia University Cancer Institute Mary Babb Randolph Cancer CenterMorgantown, West Virginia