Phase I/II Study of Preoperative Gemcitabine in Combination With Oral Hydroxychloroquine (GcHc) in Subjects With High Risk Stage IIb or III Adenocarcinoma of the Pancreas
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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To establish the safety and tolerability of a novel regimen of pre-operative oral hydroxychloroquine in combination with gemcitabine (GCHC) in patients with high risk stage IIb or III adenocarcinoma of the pancreas
The proportion of patients experiencing DLT will be calculated for each dose level, with 90% exact binomial confidence intervals. The dose-toxicity function will be estimated by means of logistic regression, with dose considered as a continuous variable, along with 90% confidence intervals. The dose with estimated probability of toxicity closest to 1/6 will be reported as the recommended Phase II dose.
During 31 days of study drug regimen
Herbert Zeh, MD
University of Pittsburgh
United States: Institutional Review Board
|UPCI/UPMC Cancer Centers||Pittsburgh, Pennsylvania 15232|