Neoadjuvant mFOLFIRINOX With Perioperative Oral Hydroxychloroquine in Resectable Pancreatic Adenocarcinoma

NCT04911816 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2103260669
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a phase I/II trial examining the safety and tolerability of pre-operative mFOLFIRINOX in combination with peri-operative oral hydroxychloroquine (FHQ) in the treatment of subjects with adenocarcinoma of the pancreas. Subjects will be staged prior to protocol entry by contrast-enhanced helical abdominal CT scan done using a pancreas mass protocol or EUS. Eligible subjects with biopsy-proven, resectable pancreatic adenocarcinoma without evidence of venous or arterial involvement on CT scan receive HCQ orally in combination with mFOLFIRINOX prior to surgery. Hydroxychloroquine will begin with the first dose of mFOLFIRINOX and continue for 2 weeks post-operatively. Three to six weeks after the last dose of mFOLFIRINOX, patients will undergo surgical exploration and pancreatectomy if technically feasible and all toxicities have resolved. Pathologic specimens will undergo detailed histopathologic and immunohistochemical evaluations with particular attention to the six surgical margins of resection: the bile duct margin (for Whipple specimens), the margin of pancreatic transection, the retroperitoneal margin, the proximal and distal duodenal margins (for Whipple specimens), and the portal vein margin along the pancreatic head (for Whipple specimens) or medial pancreas (for distal pancreatectomies). Tissue specimens will be stored at -80C for future correlative studies of autophagy and tumor response to protocol therapy. Ten to fourteen weeks following completion of successful surgical removal of their tumor, subjects will undergo repeat staging studies per standard of care. Subjects will pursue standard of care adjuvant therapy options at the discretion of their physician.

Conditions

Adenocarcinoma of the Pancreas

Outcome Measures

Primary Outcomes (2)

• Phase I - Establishing Maximum tolerated dose (MTD)

  Maximum tolerated dose (MTD) for FHQ which is defined as the highest dose level in which the investigators have treated 6 patients with at most 1 experiencing dose limiting toxicities (DLT). A maximum of 18 patients (3x6) will be accrued for dose finding.

  From first dose to 30 days after treatment has been discontinued or until death, whichever occurs first.

• Phase II - Rate of grade IIb or better histopathological response

  The number of patients that have a rate of grade IIb or better histopathological response.

  Up to 4 months

Secondary Outcomes (1)

• Phase II - To establish the potential biological activity of FHQ by biochemical tumor response, as assessed by Ca 19-9.

  2 months

Study Arms (1)

Hydroxychloroquine

EXPERIMENTAL

Hydroxychloroquine sulfate

Drug: Hydroxychloroquine sulfate

Interventions

Hydroxychloroquine sulfate DRUG

Hydroxychloroquine, oral, dose escalated (400mg, 800mg, 1200mg) beginning concurrent with mFOLFIRINOX and extending 2 weeks post-operatively. Dose will be assigned to patients using 3+3 Algorithm to identify the Maximum Dose Tolerated.

Also known as: Plaquenil

Hydroxychloroquine

Eligibility Criteria

• Age: 18 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
• Pancreatic protocol helical CT scan demonstrating absence of venous or arterial involvement, consistent with NCCN guidelines for resectable disease
• ECOG performance status ≤ 1
• 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
• 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.
• Subjects who are found to have loss-of-function mutations in DPYD or UGTA1 by Oneome pharmacogenomic testing, resulting in increased risk of mFOLFIRINOX toxicity. DPYD mutations have been noted in 5% of the overall population. Homozygous UGT1A1 mutations have been noted in 10% of North Americans.
• Prior use of radiotherapy or investigational agents for pancreatic cancer.
• Any evidence of metastasis to distant organs (liver, lung, peritoneum).
• Cross sectional imaging suggesting portal vein, superior mesenteric artery, hepatic artery involvement that would make the patient borderline resectable or locally advanced
• 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 (chloroquine, hydroxychloroquine, 5-Fluorouracil, Leucovorin, Oxaliplatin, Irinotecan).
• Other concurrent experimental therapy.
• The effects of HCQ, and mFOLFIRINOX 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 mFOLFIRINOX 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.

Sponsors & Collaborators

• West Virginia University: lead

Study Sites (1)

West Virginia University Cancer Institute Mary Babb Randolph Cancer Center

Morgantown, West Virginia, 26506, United States

RECRUITING

MeSH Terms

Interventions

Hydroxychloroquine

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Brian Boone, MD

  WVU Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brian Boone

CONTACT

304-598-4000; brian.boone@hsc.wvu.edu

Study Design

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

Study Record Dates

• First Submitted: May 24, 2021
• First Posted: June 3, 2021
• Study Start: July 16, 2021
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2030
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

US (1)