- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01128296
Study of Pre-surgery Gemcitabine + Hydroxychloroquine (GcHc) in Stage IIb or III Adenocarcinoma of the Pancreas
April 16, 2019 updated by: Amer Zureikat
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
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
Enrollment (Actual)
35
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 15232
- UPCI/UPMC Cancer Centers
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
19 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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:
- Serum creatinine level ≤1.5 the upper limits of normal
- Serum total bilirubin level ≤1.5 X ULN
- 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:
- Subjects deemed surgically unresectable or subjects unwilling to undergo surgical resection.
- Subjects who have received chemotherapy within 12 months prior to study entry.
- Prior use of radiotherapy or investigational agents for pancreatic cancer.
- Any evidence of metastasis to distant organs (liver, lung, peritoneum).
- Symptomatic or endoscopic evidence of gastric outlet obstruction
- Concurrent malignancies with evidence of active or measurable disease except basal cell carcinoma of the skin
- Inability to adhere to study and/or follow-up procedures
- History of allergic reactions or hypersensitivity to the study drugs (hydroxychloroquine, gemcitabine).
- Other concurrent experimental therapy.
- The effects of HCQ, and gemcitabine on the developing human fetus are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. All females of childbearing potential must have a blood test or urine study within two weeks prior to registration to rule out pregnancy. Should a woman become pregnant while participating in this study, she should inform her treating physician immediately. If a man impregnates a woman while participating in this study, he should inform his treating physician immediately as well.
- Because patients with immune deficiency are at increased risk of lethal infections when treated with bone marrow-suppressive therapy, HIV-positive patients are excluded from the study. For patients receiving combination anti-retroviral therapy, the potential impact of pharmacokinetic interactions with HCQ and gemcitabine is unknown. Appropriate studies may be undertaken in patients with HIV and those receiving combination anti-retroviral therapy in the future.
- Due to the risk of disease exacerbation, patients with porphyria are ineligible.
- Patients with psoriasis are ineligible unless the disease is well controlled and they are under the care of a specialist who agrees to monitor the patient for exacerbations.
- Patients requiring the use of enzyme-inducing anti-epileptic medication that includes: phenytoin, carbamazepine, phenobarbital, primidone or oxcarbazepine are excluded.
- Patients with previously documented macular degeneration or diabetic retinopathy are excluded.
- Baseline EKG with QTc >470 msec (including subjects on medication). Subjects with ventricular pacemaker for whom QT interval is not measurable will be eligible on a case-by-case basis.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Hydroxychloroquine + Gemcitabine (HcGc)
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.
Other Names:
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).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants That Experienced a Dose Limiting Toxicity (DLT)
Time Frame: Up to 31 days
|
Number of Participants at each dose level of HCQ that experienced a Dose Limiting Toxicity (DLT).
|
Up to 31 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease-free Survival (DFS)
Time Frame: Up to 30 months
|
Median number of months of disease-free survival for participants receiving study treatment.
|
Up to 30 months
|
Overall Survival (OS)
Time Frame: Up to 35 months
|
Median number of months of overall survival for participants receiving study treatment.
|
Up to 35 months
|
Disease-free Survival (DFS) by Response to HCQ Treatment
Time Frame: Up to 30 months
|
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
Time Frame: Up to 35 months
|
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
Time Frame: Up to 30 months
|
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
Time Frame: Up to 30 months
|
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
Time Frame: Up to 35 months
|
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
Time Frame: Up to 35 months
|
Up to 35 months
|
|
Overall Survival (OS) by p53 Mutant Status
Time Frame: Up to 35 months
|
Up to 35 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Herbert Zeh, MD, University of Pittsburgh
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2010
Primary Completion (Actual)
April 1, 2013
Study Completion (Actual)
July 1, 2014
Study Registration Dates
First Submitted
May 20, 2010
First Submitted That Met QC Criteria
May 20, 2010
First Posted (Estimate)
May 21, 2010
Study Record Updates
Last Update Posted (Actual)
May 1, 2019
Last Update Submitted That Met QC Criteria
April 16, 2019
Last Verified
April 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Adenocarcinoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Gemcitabine
- Hydroxychloroquine
Other Study ID Numbers
- 09-122
- PO1101944
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Pancreatic Cancer
-
Sidney Kimmel Cancer Center at Thomas Jefferson...CelgeneWithdrawnPancreatic Ductal Adenocarcinoma | Stage III Pancreatic Cancer | Stage IV Pancreatic Cancer | Stage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage IA Pancreatic Cancer | Stage IB Pancreatic CancerUnited States
-
University of NebraskaNational Cancer Institute (NCI)CompletedPancreatic Adenocarcinoma | Stage III Pancreatic Cancer | Stage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage II Pancreatic Cancer | Stage I Pancreatic Cancer | Resectable Pancreatic Carcinoma | Stage IA Pancreatic Cancer | Stage IB Pancreatic CancerUnited States
-
Virginia Commonwealth UniversityNational Cancer Institute (NCI)CompletedPancreatic Adenocarcinoma | Recurrent Pancreatic Carcinoma | Stage III Pancreatic Cancer | Stage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage IA Pancreatic Cancer | Stage IB Pancreatic CancerUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedPancreatic Adenocarcinoma | Resectable Pancreatic Cancer | Stage III Pancreatic Cancer | Stage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage IA Pancreatic Cancer | Stage IB Pancreatic Cancer | Poorly Differentiated Malignant Neoplasm | Undifferentiated Pancreatic CarcinomaUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)WithdrawnStage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage IA Pancreatic Cancer | Stage IB Pancreatic Cancer
-
National Cancer Institute (NCI)CompletedStage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage IA Pancreatic Cancer | Stage IB Pancreatic CancerUnited States
-
University of UtahNovartis PharmaceuticalsRecruitingMetastatic Pancreatic Carcinoma | Unresectable Pancreatic Carcinoma | Stage III Pancreatic Cancer | Stage IV Pancreatic Cancer | Stage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage II Pancreatic CancerUnited States
-
Shanghai Zhongshan HospitalFudan UniversityNot yet recruitingPancreatic Cancer Stage III | Pancreatic Cancer, Stage IB | Pancreatic Cancer, Stage IIA | Pancreatic Cancer, Stage IIBChina
-
University of Wisconsin, MadisonCompletedStage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage IA Pancreatic Cancer | Stage IB Pancreatic CancerUnited States
-
Fudan UniversityUnknownStage ⅠA Pancreatic Cancer | Stage ⅠB Pancreatic Cancer | Stage ⅡA Pancreatic Cancer | Stage ⅡB Pancreatic CancerChina
Clinical Trials on Hydroxychloroquine
-
Cambridge University Hospitals NHS Foundation TrustUnknown
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)WithdrawnMyelodysplastic Syndromes | Progressive DiseaseUnited States
-
Health Institutes of TurkeyCompleted
-
Peng Wang, MD PhDCompleted
-
University of MichiganCures Within ReachRecruitingRetinitis PigmentosaUnited States
-
University Hospital, MontpellierTerminatedCoronavirus Infection | Pneumonia, ViralFrance
-
Assistance Publique - Hôpitaux de ParisCompletedSARS-CoV-2 InfectionFrance
-
Hospital do CoracaoHospital Israelita Albert Einstein; Hospital Sirio-Libanes; Brazilian Research... and other collaboratorsCompletedCoronavirus InfectionsBrazil
-
Ravi Amaravadi, MDTerminatedCOVID-19United States
-
Brigham and Women's HospitalNational Heart, Lung, and Blood Institute (NHLBI)CompletedLymphangioleiomyomatosisUnited States