Gemcitabine and Leflunomide in Patients With Advanced Unresectable Pancreatic Cancer

NCT06454383 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 23540NCI-2024-04359P30CA033572
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial tests the safety, side effects, and best dose of leflunomide in combination with gemcitabine in treating patients with pancreatic cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and cannot be removed by surgery (unresectable). Improving the effectiveness of gemcitabine without increasing side effects could lead to a greater impact for pancreatic cancer patients' survival and quality of life. Gemcitabine is commonly used as a first-line chemotherapy treatment for pancreatic cancer. Leflunomide is a drug approved for use against rheumatoid arthritis that is being looked at as a cancer treatment option. It has shown promising results when combined with gemcitabine. Giving gemcitabine in combination with leflunomide may be safe and effective in treating patients with advanced unresectable pancreatic cancer.

Conditions

Advanced Pancreatic Adenocarcinoma; Stage III Pancreatic Cancer AJCC v8; Stage IV Pancreatic Cancer AJCC v8; Unresectable Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicities (DLTs)

  Toxicities will be graded according to Common Terminology Criteria for Adverse Events version 5.0.

  Up to 28 days (cycle 1)

• Incidence of adverse events

  Toxicities will be graded according to Common Terminology Criteria for Adverse Events version 5.0.

  Up to 30 days after completion of study treatment

Secondary Outcomes (4)

• Progression-free survival (PFS)

  From start of protocol treatment until progression or death, and if neither event occur, the patient is at the time of last contact, assessed up to 1 year after completion of study treatment

• Overall survival (OS)

  From start of protocol treatment until death, and if the patient is alive, the patient is censored at time of last contact, assessed up to 1 year after completion of study treatment

• Overall response rate (ORR)

  Up to 1 year after completion of study treatment

• Change in quality of life (QOL)

  Baseline to 1 year after completion of study treatment

Study Arms (1)

Treatment (gemcitabine, leflunomide)

EXPERIMENTAL

Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 of each cycle and leflunomide PO QD on days -3 to -1 prior to cycle 1 and days 1-28 of each cycle thereafter. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive cholestyramine PO TID for 11 days at the end of treatment in the absence of unacceptable toxicity. Patients also undergo CT, MRI, or other imaging scans as clinically indicated throughout the study, as well as blood sample collection on study and during follow up.

Procedure: Biospecimen Collection; Drug: Cholestyramine; Procedure: Computed Tomography; Procedure: Diagnostic Imaging; Drug: Gemcitabine; Drug: Leflunomide; Procedure: Magnetic Resonance Imaging

Interventions

Cholestyramine DRUG

Given PO

Also known as: Cholybar, Colestyramine, Duolite AP143 Resin, Questran, Questran Light

Treatment (gemcitabine, leflunomide)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (gemcitabine, leflunomide)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (gemcitabine, leflunomide)

Diagnostic Imaging PROCEDURE

Undergo imaging scans

Also known as: Medical Imaging

Treatment (gemcitabine, leflunomide)

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Treatment (gemcitabine, leflunomide)

Leflunomide DRUG

Given PO

Also known as: Arava, SU101

Treatment (gemcitabine, leflunomide)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (gemcitabine, leflunomide)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative.
• Adult patients lacking capacity to consent may participate if they have a caretaker that could ensure oral medication compliance.
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies.
• If unavailable, exceptions may be granted with study principal investigator (PI) approval.
• Age: ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) ≤ 1.
• Subjects must have histologically or cytologically confirmed diagnosis of advanced unresectable pancreatic ductal adenocarcinoma (PDA).
• Measurable or evaluable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
• Potential patients must have plans of receiving single agent gemcitabine.
• Fully recovered from the acute toxic effects (except alopecia or neuropathy) to ≤ grade 1 to prior anti-cancer therapy.
• Without bone marrow involvement: Absolute neutrophil count (ANC) ≥ 1,500/mm\^3 NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement.
• Without bone marrow involvement: Platelets ≥ 100,000/mm\^3 NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement.
• Hemoglobin ≥ 9g/dL NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment unless cytopenia is secondary to disease involvement.
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin levels \> 1.5 x ULN (unless has Gilbert's disease total bilirubin ≤ 3 x ULN)
• Aspartate aminotransferase (AST) ≤ 1.5 x ULN OR if liver metastases ≤ 3 x ULN

You may not qualify if:

• Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days prior to day 1 of protocol therapy.
• Drugs metabolized by CYP2C8, CYP1A2, BCRP, OATP1B1/B3, and OAT3 transporters within 21 days prior to day 1 of protocol therapy.
• Herbal medications (excluding cannabidiol \[CBD\]).
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent.
• Issues with tolerating oral medication (e.g. inability to swallow pills, malabsorption issues, ongoing nausea or vomiting).
• Positive for tuberculosis or latent tuberculosis (TB).
• Active diarrhea.
• Clinically significant uncontrolled illness.
• Active infection requiring antibiotics.
• Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection. (\*If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable.)
• Diagnosis of Gilbert's disease.
• Prior malignancy other than carcinoma in situ of the cervix, or nonmelanoma skin cancer, unless that prior malignancy was diagnosed and definitively treated 5 or more years prior to study entry with no subsequent evidence of recurrence. Patients with a history of low grade (Gleason score ≤ 6 = Gleason group 1) localized prostate cancer will be eligible even if diagnosed less than 5 years prior to study entry. Other malignancies with low probability of recurrence may be allowed with PI approval.
• Females only: Pregnant or breastfeeding.
• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Specimen Handling; Cholestyramine Resin; X-Rays; Gemcitabine; Leflunomide; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Polystyrenes; Plastics; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Isoxazoles; Azoles; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Vincent Chung

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 6, 2024
• First Posted: June 12, 2024
• Study Start: May 13, 2024
• Primary Completion (Estimated): November 13, 2026
• Study Completion (Estimated): November 13, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

US (1)