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Pancreatic CancerPhase 1/2NCT01128296

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

A Phase 1/2 study testing Hydroxychloroquine and Gemcitabine in people with Pancreatic Cancer, run by Amer Zureikat at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
Pancreatic Cancer
What is being tested?
Hydroxychloroquine and Gemcitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
1 siteUnited States
Study dates
Oct 2010to Jul 2014
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UPCI/UPMC Cancer Centers

    Pittsburgh, Pennsylvania, 15232

Other trials in United States

About this study

Official title: 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.

Read the 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.

Keywords
high risk stage IIb or III adenocarcinoma of the pancreas
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HydroxychloroquineDrug

    Also called Plaquenil

    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.

  • GemcitabineDrug

    Also called Gemzar

    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).

Study groups in NCT01128296
Study groupRoleWhat they receive
Hydroxychloroquine + Gemcitabine (HcGc)ExperimentalHydroxychloroquine orally twice daily in combination with gemcitabine for 31 days prior to surgical resection
Receives: Drug: Hydroxychloroquine; Drug: Gemcitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: Up to 31 days

Secondary outcomes (9)

  1. Disease-free Survival (DFS)

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

    Measured: Up to 30 months

  2. Overall Survival (OS)

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

    Measured: Up to 35 months

  3. 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.

    Measured: Up to 30 months

  4. 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.

    Measured: Up to 35 months

  5. 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)

    Measured: Up to 30 months

  6. 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%.

    Measured: Up to 30 months

  7. 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%.

    Measured: Up to 35 months

  8. Disease-free Survival by p53 Genetic Status

    Measured: Up to 35 months

  9. Overall Survival (OS) by p53 Mutant Status

    Measured: Up to 35 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 May 2010 (estimated)
  2. Study startOct 2010
  3. Primary completionApr 2013
  4. Study completionJul 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01128296
Sponsor's protocol ID
09-122
Other IDs
PO1101944
Status last verified
Apr 2019
First submitted
20 May 2010
Last updated
1 May 2019
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 29929491

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Hydroxychloroquine and Gemcitabine in people with Pancreatic Cancer, run by Amer Zureikat at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants That Experienced a Dose Limiting Toxicity (DLT) (time frame: Up to 31 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01128296, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2019.

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