Gemcitabine and Leflunomide in Patients with Advanced Unresectable Pancreatic Cancer

Inclusion Criteria

• 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) ≤ 2 x ULN OR if liver metastases ≤ 3 x ULN
• Alanine aminotransferase (ALT) ≤ 2 x ULN OR if liver metastases ≤ 2 x ULN
• Creatinine ≤ 1.5 x ULN OR creatinine clearance (Cockcroft Gault) of ≥ 50 mL/min for participants with a creatinine level of > 1.5 x ULN.
• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of gemcitabine therapy for women and at least 3 months after the last dose of gemcitabine therapy for men, and/or undergo drug elimination of leflunomide at end of treatment until leflunomide is undetectable in the plasma. * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only).

Exclusion Criteria

• Chemotherapy, radiation therapy, biological therapy, immunotherapy 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).