The primary goal of the research study is to determine whether treating pancreatic cancer patients with hydroxychloroquine in combination with gemcitabine before surgery is safe. The secondary goal is to determine if this new treatment regimen can effectively treat pancreatic cancer. This study will test the safety and efficacy of this combination in two parts, or phases.
This is a phase I/II trial designed to assess the safety, tolerability and efficacy of neoadjuvant oral hydroxychloroquine (Plaquenil®) in combination with FDR gemcitabine in subjects with high risk IIb or III adenocarcinoma of the pancreas. Eligible subjects will be administered hydroxychloroquine orally once or twice daily (depending on dose) in combination with FDR gemcitabine (on days 1 and 15) for 31 days prior to surgical resection. Dose escalations of hydroxychloroquine will proceed using Storer's Up-and-Down algorithm D. Subjects will be monitored for side effects and tolerability of the drug. Pre- and post-treatment PET scans will be the primary means to assess response to therapy. Resected tumors will also be assessed for evidence of inhibition of autophagy as well as histopathologic response and margin negative resection and number of positive lymph nodes.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Oral dosing daily starting at 48 hours before first dose of gemcitabine (starting on Day -2) and for a total of 31 days (ending on Day 29), prior to surgical resection. Capsules are available in 200 mg strengths. Daily doses are 200, 400, 600, 800, 1000, or 1200 mg, and will be administered BID for doses above 200 mg.
Intravenous administration on Days 1 and 15, with the infusion given at the fixed dose rate of 10mg/m2/min (e.g. 150 min for a 1500 mg/m2 dose).
UPCI/UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States
Number of Participants That Experienced a Dose Limiting Toxicity (DLT)
Number of Participants at each dose level of HCQ that experienced a Dose Limiting Toxicity (DLT).
Time frame: Up to 31 days
Disease-free Survival (DFS)
Median number of months of disease-free survival for participants receiving study treatment.
Time frame: Up to 30 months
Overall Survival (OS)
Median number of months of overall survival for participants receiving study treatment.
Time frame: Up to 35 months
Disease-free Survival (DFS) by Response to HCQ Treatment
Median number of months of disease-free survival in participants who did and did not experience response to HCQ treatment. Patients who had \>51 % increase in their LC3-II staining were classified as having a response to HCQ.
Time frame: Up to 30 months
Overall Survival (OS) by Response to HCQ Treatment
Median number of months of overall survival in participants who did and did not experience response to HCQ treatment. Patients who had \>51 % increase in their LC3-II staining were classified as having a response to HCQ.
Time frame: Up to 35 months
R0 Resection Rate
Number of participants that underwent a resection with microscopically margin-negative resection in which no gross or microscopic tumor remains in the primary tumor bed (24) / number of that completed treatment (31)
Time frame: Up to 30 months
Disease-free Survival (DFS) by CA 19-9 Response
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Median number of months of disease-free survival for participants who experienced Ca 19-9 (surrogate biomarker) response (either an increase or decrease in Ca 19-9), or no Ca 19-9 response. Per participant increases in Ca 19-9 ranged from \>0 to 225%. Per participant decreases in Ca 19-9 ranged from \>0 to 100%.
Time frame: Up to 30 months
Overall Survival (OS) by CA 19-9 Response
Median number of months of overall survival for participants who experienced Ca 19-9 (surrogate biomarker) response (either an increase or decrease in Ca 19-9), or, no Ca 19-9 response. Per participant increases in Ca 19-9 ranged from \>0 to 225%. Per participant decreases in Ca 19-9 ranged from \>0 to 100%.
Time frame: Up to 35 months
Disease-free Survival by p53 Genetic Status
Time frame: Up to 35 months
Overall Survival (OS) by p53 Mutant Status
Time frame: Up to 35 months