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

NCT01128296 | Completed Phase 1 Results DMC

• 2 other identifiers: 09-122PO1101944
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pancreatic Cancer

Keywords

high risk stage IIb or III adenocarcinoma of the pancreas

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (9)

• Disease-free Survival (DFS)

  Up to 30 months

• Overall Survival (OS)

  Up to 35 months

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

  Up to 30 months

• Overall Survival (OS) by Response to HCQ Treatment

  Up to 35 months

• R0 Resection Rate

  Up to 30 months

Study Arms (1)

Hydroxychloroquine + Gemcitabine (HcGc)

EXPERIMENTAL

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

Drug: Hydroxychloroquine; Drug: Gemcitabine

Interventions

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.

Also known as: Plaquenil

Hydroxychloroquine + Gemcitabine (HcGc)

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).

Also known as: Gemzar

Hydroxychloroquine + Gemcitabine (HcGc)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amer Zureikat: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

UPCI/UPMC Cancer Centers

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

• 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.

  PMID: 29929491 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Hydroxychloroquine; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Herbert Zeh, MD
• Organization: UPMC CancerCenter

zehxhx@upmc.edu

412-692-2852

Study Officials

• Herbert Zeh, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 20, 2010
• First Posted: May 21, 2010
• Study Start: October 1, 2010
• Primary Completion: April 1, 2013
• Study Completion: July 1, 2014
• Last Updated: May 1, 2019
• Results First Posted: July 6, 2017

Record last verified: 2019-04

Locations

US (1)