Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| PO1101944 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hydroxychloroquine + Gemcitabine (HcGc) | Experimental | Hydroxychloroquine orally twice daily in combination with gemcitabine for 31 days prior to surgical resection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hydroxychloroquine | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Up to 31 days |
| Measure | Description | Time Frame |
|---|---|---|
| Disease-free Survival (DFS) | Median number of months of disease-free survival for participants receiving study treatment. | Up to 30 months |
| Overall Survival (OS) | Median number of months of overall survival for participants receiving study treatment. |
Not provided
Inclusion Criteria:
Subjects with biopsy-proven adenocarcinoma of the pancreas
staged by IIb or greater by by EUS, or tumor greater than 2.6 cm on EUS or pancreatic protocol helical CT scan demonstrating venous involvement
Karnofsky performance status >/= 70.
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:
White blood cell count >/= 3.5x109/ml per ml and platelet count ≥ 100x109 per ml
Age >18 years.
For subjects with obstructive jaundice, the biliary tract must be drained with a temporary plastic or a short permanent metallic biliary stent.
Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Herbert Zeh, MD | University of Pittsburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UPCI/UPMC Cancer Centers | Pittsburgh | Pennsylvania | 15232 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29929491 | Derived | Boone BA, Murthy P, Miller-Ocuin J, Doerfler WR, Ellis JT, Liang X, Ross MA, Wallace CT, Sperry JL, Lotze MT, Neal MD, Zeh HJ 3rd. Chloroquine reduces hypercoagulability in pancreatic cancer through inhibition of neutrophil extracellular traps. BMC Cancer. 2018 Jun 22;18(1):678. doi: 10.1186/s12885-018-4584-2. |
Not provided
Not provided
35 enrolled
2 participants withdrew prior to treatment
1 participants removed from protocol after the first dose of gemcitabine due to cerebrovascular accident unrelated to study drug
1 patient removed from protocol due to allergic rash likely related to gemcitabine
31 participants remained to receive gemcitabine + HCQ treatment
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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 200 mg/day taken for 31 consecutive days until the day of surgery. |
| FG001 | 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 400 mg/day taken for 31 consecutive days until the day of surgery. |
| FG002 | 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 600 mg/day taken for 31 consecutive days until the day of surgery. |
| FG003 | 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 800 mg/day taken for 31 consecutive days until the day of surgery. |
| FG004 | 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 1000 mg/day taken for 31 consecutive days until the day of surgery. |
| FG005 | Preoperative Gemcitabine (1500 mg/m^2) + HCQ (1200 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Preoperative Gemcitabine (1500 mg/m^2) + HCQ (≤1200 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 (maximum dose of 1200 mg/day) taken for 31 consecutive days until the day of surgery. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Observed for dose-limiting toxicities or treatment delays attributed to HCQ to determine the maximum tolerated dose. | Posted | Number | participants | Up to 31 days |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Preoperative Gemcitabine (1500 mg/m^2) + HCQ (≤1200 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 (maximum dose of 1200 mg/day) taken for 31 consecutive days until the day of surgery. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infection with Grade 3-4 neutrophils (ANC <1.0x10^9/L), Abdomen NOS | Infections and infestations |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukocytes (total WBC) | Blood and lymphatic system disorders |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Herbert Zeh, MD | UPMC CancerCenter | 412-692-2852 | zehxhx@upmc.edu |
Not provided
| ID | Term |
|---|---|
| D010190 | Pancreatic Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| D006886 | Hydroxychloroquine |
| D000093542 | Gemcitabine |
| ID | Term |
|---|---|
| D002738 | Chloroquine |
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Gemcitabine | Drug | 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). |
|
|
| 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. | 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. | 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) | Up to 30 months |
| Disease-free Survival (DFS) by CA 19-9 Response | 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%. | 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%. | Up to 35 months |
| Disease-free Survival by p53 Genetic Status | Up to 35 months |
| Overall Survival (OS) by p53 Mutant Status | Up to 35 months |
| Withdrawal by Subject |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
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. |
| OG002 | 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 600 mg/day taken for 31 consecutive days until the day of surgery. |
| OG003 | 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 800 mg/day taken for 31 consecutive days until the day of surgery. |
| OG004 | 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 1000 mg/day taken for 31 consecutive days until the day of surgery. |
| OG005 | Preoperative Gemcitabine (1500 mg/m^2) + HCQ (1200 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. |
|
|
| Secondary | Disease-free Survival (DFS) | Median number of months of disease-free survival for participants receiving study treatment. | Participants that completed more than 80 % of the intended dose of HCQ. | Posted | Median | 95% Confidence Interval | months | Up to 30 months |
|
|
|
| Secondary | Overall Survival (OS) | Median number of months of overall survival for participants receiving study treatment. | Participants that completed more than 80% of the intended dose of HCQ. | Posted | Median | 95% Confidence Interval | months | Up to 35 months |
|
|
|
| Secondary | 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. | Subset of participants that completed more than 80% of the intended dose of HCQ treatment. | Posted | Median | 95% Confidence Interval | months | Up to 30 months |
|
|
|
| Secondary | 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. | Subset of participants that completed more than 80 % of the intended dose of HCQ. | Posted | Median | 95% Confidence Interval | months | Up to 35 months |
|
|
|
| Secondary | 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) | Participants that completed more than 80 % of the intended dose of HCQ. | Posted | Number | percentage of participants | Up to 30 months |
|
|
|
| Secondary | Disease-free Survival (DFS) by CA 19-9 Response | 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%. | 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. | Posted | Median | 95% Confidence Interval | months | Up to 30 months |
|
|
|
| Secondary | 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%. | 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 | Posted | Median | 95% Confidence Interval | months | Up to 35 months |
|
|
|
| Secondary | Disease-free Survival by p53 Genetic Status | Participants that completed more than 80 % of the intended dose of HCQ. | Posted | Median | 95% Confidence Interval | months | Up to 35 months |
|
|
|
| Secondary | Overall Survival (OS) by p53 Mutant Status | Participants that completed more than 80 % of the intended dose of HCQ. | Posted | Median | 95% Confidence Interval | months | Up to 35 months |
|
|
|
| 4 |
| 35 |
| 34 |
| 35 |
| Infection with Grade 3-4 neutrophils (ANC <1.0x10^9/L), Biliary tree | Infections and infestations |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, Urinary tract NOS | Infections and infestations |
|
| Thrombosis/thrombus/embolism | Vascular disorders |
|
| Neutrophils/granulocytes (ANC/AGC) | Blood and lymphatic system disorders |
|
| Platelets | Blood and lymphatic system disorders |
|
| Hemoglobin | Blood and lymphatic system disorders |
|
| Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) | General disorders |
|
| Weight loss | General disorders |
|
| Fatigue (asthenia, lethargy, malaise) | General disorders |
|
| Pruritus/itching | Skin and subcutaneous tissue disorders |
|
| Rash: acne/acneiform | Skin and subcutaneous tissue disorders |
|
| Rash: dermatitis associated with radiation, Chemoradiation | Skin and subcutaneous tissue disorders |
|
| Dermatology/Skin - Other (Specify, __) | Skin and subcutaneous tissue disorders |
|
| Distension/bloating, abdominal | Gastrointestinal disorders |
|
| Gastrointestinal - Other (Specify, __) | Gastrointestinal disorders |
|
| Vomiting | Gastrointestinal disorders |
|
| Anorexia | Gastrointestinal disorders |
|
| Diarrhea | Gastrointestinal disorders |
|
| Constipation | Gastrointestinal disorders |
|
| Nausea | Gastrointestinal disorders |
|
| Hepatobiliary/Pancreas - Other (Specify, __) | Hepatobiliary disorders |
|
| Calcium, serum-low (hypocalcemia) | Metabolism and nutrition disorders |
|
| Creatinine | Metabolism and nutrition disorders |
|
| Phosphate, serum-low (hypophosphatemia) | Metabolism and nutrition disorders |
|
| Potassium, serum-high (hyperkalemia) | Metabolism and nutrition disorders |
|
| Bilirubin (hyperbilirubinemia) | Metabolism and nutrition disorders |
|
| Potassium, serum-low (hypokalemia) | Metabolism and nutrition disorders |
|
| Glucose, serum-high (hyperglycemia) | Metabolism and nutrition disorders |
|
| Alkaline phosphatase | Metabolism and nutrition disorders |
|
| ALT, SGPT (serum glutamic pyruvic transaminase) | Metabolism and nutrition disorders |
|
| Sodium, serum-low (hyponatremia) | Metabolism and nutrition disorders |
|
| AST, SGOT(serum glutamic oxaloacetic transaminase) | Metabolism and nutrition disorders |
|
| Albumin, serum-low (hypoalbuminemia) | Metabolism and nutrition disorders |
|
| Mood alteration, Anxiety | Nervous system disorders |
|
| Pain - Other (Specify, __) | General disorders |
|
| Pain, Abdomen NOS | General disorders |
|
Not provided
Not provided
Not provided
| D004066 |
| Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |