Study of Pre-surgery Gemcitabine + Hydroxychloroquine (GcHc) in Stage IIb or III Adenocarcinoma of the Pancreas

Brief summary public domain (ClinicalTrials.gov)

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.

Detailed description public domain (ClinicalTrials.gov)

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.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Number of Participants That Experienced a Dose Limiting Toxicity (DLT) [Up to 31 days]. Number, participants. Preoperative Gemcitabine (1500 mg/m^2) + HCQ (200 mg/Day) (n=1): 0; Preoperative Gemcitabine (1500 mg/m^2) + HCQ (400 mg/Day) (n=1): 0; Preoperative Gemcitabine (1500 mg/m^2) + HCQ (600 mg/Day) (n=1): 0; Preoperative Gemcitabine (1500 mg/m^2) + HCQ (800 mg/Day) (n=1): 0; Preoperative Gemcitabine (1500 mg/m^2) + HCQ (1000 mg/Day) (n=1): 0; Preoperative Gemcitabine (1500 mg/m^2) + HCQ (1200 mg/Day) (n=26): 0.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Disease-free Survival (DFS) [Up to 30 months]. Median, months (95% Confidence Interval). Preoperative Gemcitabine (1500 mg/m^2) + HCQ (1200 mg/Day) (n=31): 11.97 (7.27 to 22.43).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Survival (OS) [Up to 35 months]. Median, months (95% Confidence Interval). Preoperative Gemcitabine (1500 mg/m^2) + HCQ (≤1200 mg/Day) (n=31): 34.83 (11.57 to NA) [Upper bound of CI not reached due to too few events.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Disease-free Survival (DFS) by Response to HCQ Treatment [Up to 30 months]. Median, months (95% Confidence Interval). Response to HQC treatment: Preoperative Gemcitabine (1500 mg/m^2) + HCQ (≤1200 mg/Day) (n=17): 15.03 (6.8 to NA) [Upper bound not reached due to too few events.]. No response to HQC treatment: Preoperative Gemcitabine (1500 mg/m^2) + HCQ (≤1200 mg/Day) (n=17): 6.9 (0.2 to NA) [Upper bound not reached due to too few events.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Survival (OS) by Response to HCQ Treatment [Up to 35 months]. Median, months (95% Confidence Interval). Response to HQC treatment: Preoperative Gemcitabine (1500 mg/m^2) + HCQ (≤1200 mg/Day) (n=17): 34.83 (11.7 to NA) [Upper bound of CI not reached due to too few events.]. No response to HQC treatment: Preoperative Gemcitabine (1500 mg/m^2) + HCQ (≤1200 mg/Day) (n=17): 10.83 (0.02 to NA) [Upper bound of CI not reached due to too few events.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

R0 Resection Rate [Up to 30 months]. Number, percentage of participants. Preoperative Gemcitabine (1500 mg/m^2) + HCQ (≤1200 mg/Day) (n=31): 77.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Disease-free Survival (DFS) by CA 19-9 Response [Up to 30 months]. Median, months (95% Confidence Interval). Ca 19-9 Response: Preoperative Gemcitabine (1500 mg/m^2) + HCQ (≤1200 mg/Day) (n=26): 21.4 (9.1 to 24.2). No Ca 19-9 Response: Preoperative Gemcitabine (1500 mg/m^2) + HCQ (≤1200 mg/Day) (n=26): 6.9 (2.3 to 9.7).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Survival (OS) by CA 19-9 Response [Up to 35 months]. Median, months (95% Confidence Interval). Ca 19-9 Response (increase or decrease): Preoperative Gemcitabine (1500 mg/m^2) + HCQ (≤1200 mg/Day) (n=26): 34.8 (11.7 to NA) [Upper bound of CI not reached due to too few events.]. No Ca 19-9 Response: Preoperative Gemcitabine (1500 mg/m^2) + HCQ (≤1200 mg/Day) (n=26): 8.8 (5.6 to NA) [Upper bound of CI not reached due to too few events.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Disease-free Survival by p53 Genetic Status [Up to 35 months]. Median, months (95% Confidence Interval). p53 WT: Preoperative Gemcitabine (1500 mg/m^2) + HCQ (≤1200 mg/Day) (n=31): 21.4 (5.5 to NA) [Upper bound of CI not reached due to too few events.]. p53 Mutant: Preoperative Gemcitabine (1500 mg/m^2) + HCQ (≤1200 mg/Day) (n=31): 11.8 (6.9 to NA) [Upper bound of CI not reached due to too few events.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Survival (OS) by p53 Mutant Status [Up to 35 months]. Median, months (95% Confidence Interval). p53 WT: Preoperative Gemcitabine (1500 mg/m^2) + HCQ (≤1200 mg/Day) (n=31): NA (5.5 to NA) [Median and Upper bound of CI not reached due to too few events.]. p53 Mutant: Preoperative Gemcitabine (1500 mg/m^2) + HCQ (≤1200 mg/Day) (n=31): 26.1 (8.8 to NA) [Upper bound of CI not reached due to too few events.].