Trial Title:
Gemcitabine and Leflunomide in Patients With Advanced Unresectable Pancreatic Cancer
NCT ID:
NCT06454383
Condition:
Advanced Pancreatic Adenocarcinoma
Stage III Pancreatic Cancer AJCC v8
Stage IV Pancreatic Cancer AJCC v8
Unresectable Pancreatic Ductal Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Pancreatic Neoplasms
Gemcitabine
Cholestyramine Resin
Leflunomide
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (gemcitabine, leflunomide)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Drug
Intervention name:
Cholestyramine
Description:
Given PO
Arm group label:
Treatment (gemcitabine, leflunomide)
Other name:
Cholybar
Other name:
Colestyramine
Other name:
Duolite AP143 Resin
Other name:
Questran
Other name:
Questran Light
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (gemcitabine, leflunomide)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Diagnostic Imaging
Description:
Undergo imaging scans
Arm group label:
Treatment (gemcitabine, leflunomide)
Other name:
Medical Imaging
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
Given IV
Arm group label:
Treatment (gemcitabine, leflunomide)
Other name:
dFdC
Other name:
dFdCyd
Other name:
Difluorodeoxycytidine
Intervention type:
Drug
Intervention name:
Leflunomide
Description:
Given PO
Arm group label:
Treatment (gemcitabine, leflunomide)
Other name:
Arava
Other name:
SU101
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (gemcitabine, leflunomide)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
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.
Detailed description:
PRIMARY OBJECTIVE:
I. To evaluate the safety and tolerability of gemcitabine in combination with leflunomide
and determine the recommended Phase 2 dose (RP2D) of the combination.
SECONDARY OBJECTIVES:
I. To evaluate the progression-free (PFS) and overall survival (OS). II. To evaluate the
overall response rate (ORR), including confirmed and unconfirmed, complete and partial
response and stable disease.
III. To describe quality of life utilizing the Functional Assessment of Cancer Therapy:
General (FACT-G) questionnaire.
EXPLORATORY OBJECTIVES:
I. To describe the pharmacokinetic profile of leflunomide when given in combination with
gemcitabine.
II. To examine the relationship between pharmacokinetics and disease progression.
OUTLINE:
Patients receive gemcitabine intravenously (IV) over 30 minutes on days 1, 8, and 15 of
each cycle and leflunomide orally (PO) once daily (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
three times a day (TID) for 11 days at the end of treatment in the absence of
unacceptable toxicity. Patients also undergo computed tomography (CT), magnetic resonance
imaging (MRI), or other imaging scans as clinically indicated throughout the study, as
well as blood sample collection on study and during follow up.
After completion of study treatment, patients are followed up at 30 days then up to 1
year.
Criteria for eligibility:
Criteria:
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) ≤ 1.5 x ULN OR if liver metastases ≤ 3 x ULN
- Alanine aminotransferase (ALT) ≤ 1.5 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.
- 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).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Medical Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Vincent Chung
Phone:
626-218-9200
Email:
vchung@coh.org
Investigator:
Last name:
Vincent Chung
Email:
Principal Investigator
Start date:
May 13, 2024
Completion date:
November 13, 2026
Lead sponsor:
Agency:
City of Hope Medical Center
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
City of Hope Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06454383
