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Hydroxychloroquine orally twice daily in combination with gemcitabine for 31 days prior to surgical resection

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).

Herbert Zeh, MD

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

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

Number of Participants at each dose level of HCQ that experienced a Dose Limiting Toxicity (DLT).

Median number of months of disease-free survival for participants receiving study treatment.

Median number of months of overall survival for participants receiving study 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.

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.

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)

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%.

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%.

National Institutes of Health (NIH)

Amer Zureikat

Assistant Professor

Participants wtih pancreatic adenocarcinoma treated with two doses of fixed dose gemcitabine (1500 mg/m\^2) administered (study days 3 and 17) in combination with oral HCQ (maximum dose of 1200 mg/day) taken for 31 consecutive days until the day of surgery.

Preoperative Gemcitabine (1500 mg/m^2) + HCQ (≤1200 mg/Day)

Age, Continuous

Sex: Female, Male

Participants wtih pancreatic adenocarcinoma treated with two doses of fixed dose gemcitabine (1500 mg/m\^2) administered (study days 3 and 17) in combination with oral HCQ dose of 200 mg/day taken for 31 consecutive days until the day of surgery.

Preoperative Gemcitabine (1500 mg/m^2) + HCQ (200 mg/Day)

Participants wtih pancreatic adenocarcinoma treated with two doses of fixed dose gemcitabine (1500 mg/m\^2) administered (study days 3 and 17) in combination with oral HCQ dose of 400 mg/day taken for 31 consecutive days until the day of surgery.

Preoperative Gemcitabine (1500 mg/m^2) + HCQ (400 mg/Day)

Participants wtih pancreatic adenocarcinoma treated with two doses of fixed dose gemcitabine (1500 mg/m\^2) administered (study days 3 and 17) in combination with oral HCQ dose of 600 mg/day taken for 31 consecutive days until the day of surgery.

Preoperative Gemcitabine (1500 mg/m^2) + HCQ (600 mg/Day)

Participants wtih pancreatic adenocarcinoma treated with two doses of fixed dose gemcitabine (1500 mg/m\^2) administered (study days 3 and 17) in combination with oral HCQ dose of 800 mg/day taken for 31 consecutive days until the day of surgery.

Preoperative Gemcitabine (1500 mg/m^2) + HCQ (800 mg/Day)

Participants wtih pancreatic adenocarcinoma treated with two doses of fixed dose gemcitabine (1500 mg/m\^2) administered (study days 3 and 17) in combination with oral HCQ dose of 1000 mg/day taken for 31 consecutive days until the day of surgery.

Preoperative Gemcitabine (1500 mg/m^2) + HCQ (1000 mg/Day)

Participants wtih pancreatic adenocarcinoma treated with two doses of fixed dose gemcitabine (1500 mg/m\^2) administered (study days 3 and 17) in combination with oral HCQ dose of 1200 mg/day taken for 31 consecutive days until the day of surgery.

Preoperative Gemcitabine (1500 mg/m^2) + HCQ (1200 mg/Day)

Observed for dose-limiting toxicities or treatment delays attributed to HCQ to determine the maximum tolerated dose.

Number of Participants That Experienced a Dose Limiting Toxicity (DLT)

Participants with pancreatic adenocarcinoma treated with two doses of fixed dose gemcitabine (1500 mg/m\^2) administered (study days 3 and 17) in combination with oral HCQ (1200 mg/day) taken for 31 consecutive days until the day of surgery.

Participants that completed more than 80 % of the intended dose of HCQ.

Disease-free Survival (DFS)

Participants that completed more than 80% of the intended dose of HCQ.

Overall Survival (OS)

Response to HQC treatment

No response to HQC treatment

Subset of participants that completed more than 80% of the intended dose of HCQ treatment.

Disease-free Survival (DFS) by Response to HCQ Treatment

Subset of participants that completed more than 80 % of the intended dose of HCQ.

Overall Survival (OS) by Response to HCQ Treatment

R0 Resection Rate

Ca 19-9 Response

No Ca 19-9 Response

Analysis population included a total of 26 participants who received study treatment, who experienced either an increase or decrease in Ca 19-9, or no Ca 19-9 surrogate biomarker response.

Disease-free Survival (DFS) by CA 19-9 Response

Ca 19-9 Response (increase or decrease)

Analysis population included participants who received study treatment, who experienced either an increase or decrease in Ca 19-9, or no Ca 19-9 surrogate biomarker response

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Pre-surgery Gemcitabine + Hydroxychloroquine (GcHc) in Stage IIb or III Adenocarcinoma of the Pancreas	NCT01128296	Pancreatic Canc...	Hydroxychloroqu... Gemcitabine	19 Years -	University of Pittsburgh
Study of Pre-surgery Gemcitabine + Hydroxychloroquine (GcHc) in Stage IIb or III Adenocarcinoma of the Pancreas	NCT01128296	Pancreatic Canc...	Hydroxychloroqu... Gemcitabine	19 Years -	University of Pittsburgh

Spots Global Cancer Trial Database for high risk stage iib or iii adenocarcinoma of the pancreas