Advanced Pancreatic AdenocarcinomaPhase 1NCT06454383
Gemcitabine and Leflunomide in Patients With Advanced Unresectable Pancreatic Cancer
A Phase 1 study testing Biospecimen Collection, Cholestyramine and Computed Tomography in people with Advanced Pancreatic Adenocarcinoma and Stage III Pancreatic Cancer AJCC v8, run by City of Hope Medical Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Pancreatic Adenocarcinoma, Stage III Pancreatic Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8
- What is being tested?
- Biospecimen Collection, Cholestyramine and Computed Tomography
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jun 2024to 13 Nov 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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).
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- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
City of Hope Medical Center
Duarte, California, 91010
Vincent Chung, 626-218-9200, vchung@coh.org
Vincent Chung
About this study
Official title: A Phase 1b Study of Gemcitabine and Leflunomide in Patients With Unresectable Pancreatic Cancer
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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:
- 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.
- Conditions
- Advanced Pancreatic Adenocarcinoma, Stage III Pancreatic Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8, Unresectable Pancreatic Ductal Adenocarcinoma
- Being tested
- Biospecimen Collection, Cholestyramine, Computed Tomography, Diagnostic Imaging, Gemcitabine
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection
CholestyramineDrug
Also called Cholybar, Colestyramine, Duolite AP143 Resin, Questran
Given PO
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
Diagnostic ImagingProcedure or surgery
Also called Medical Imaging
Undergo imaging scans
GemcitabineDrug
Also called dFdC, dFdCyd, Difluorodeoxycytidine
Given IV
LeflunomideDrug
Also called Arava, SU101
Given PO
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Biospecimen Collection; Drug: Cholestyramine; Procedure: Computed Tomography; Procedure: Diagnostic Imaging; Drug: Gemcitabine; Drug: Leflunomide; Procedure: Magnetic Resonance Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicities (DLTs)
Toxicities will be graded according to Common Terminology Criteria for Adverse Events version 5.0.
Measured: 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.
Measured: Up to 30 days after completion of study treatment
Secondary outcomes (4)
Progression-free survival (PFS)
PFS will be estimated using the Kaplan-Meier product-limit method.
Measured: 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)
OS will be estimated using the Kaplan-Meier product limit method.
Measured: 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)
ORR will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.
Measured: Up to 1 year after completion of study treatment
Change in quality of life (QOL)
Change in QOL will be measured by the Functional Assessment of Cancer Therapy: General (FACT-G) questionnaire.
Measured: Baseline to 1 year after completion of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2024
- Study start10 Jun 2024
- Primary completion13 Nov 2026 (estimated)
- Study completion13 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Pancreatic AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (estimated)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Vincent Chung, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06454383
- Sponsor's protocol ID
- 23540
- Other IDs
- NCI-2024-04359, 23540, P30CA033572
- Status last verified
- Oct 2026
- First submitted
- 6 Jun 2024
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study of Gemcitabine and Leflunomide in Patients With Unresectable Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT06454383
- Acronym / sponsor ID
- 23540
- Conditions
- Advanced Pancreatic Adenocarcinoma, Stage III Pancreatic Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8, Unresectable Pancreatic Ductal Adenocarcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 19 participants (estimated)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 10 Jun 2024 (actual)
- Primary completion
- 13 Nov 2026 (estimated)
- Study completion
- 13 Nov 2026 (estimated)
- First posted
- 12 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (gemcitabine, leflunomide) | Experimental | Procedure: Biospecimen Collection, Drug: Cholestyramine, Procedure: Computed Tomography, Procedure: Diagnostic Imaging, Drug: Gemcitabine, Drug: Leflunomide, Procedure: Magnetic Resonance ImagingPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Documented informed consent of the participant and/or legally authorized representative.
- Agreement to allow the use of archival tissue from diagnostic tumor biopsies.
- Age: ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) ≤ 1.
- Subjects must have histologically or cytologically confirmed diagnosis of advanced unresectable pancreatic ductal adenocarcinoma (PDA).
Key exclusion criteria (15 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Specimen CollectionUndergo blood sample collection | Procedure or surgery | Treatment (gemcitabine, leflunomide) |
| CholestyramineAlso: Cholybar, Colestyramine, Duolite AP143 Resin, QuestranGiven PO | Drug | Treatment (gemcitabine, leflunomide) |
| Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo CT | Procedure or surgery | Treatment (gemcitabine, leflunomide) |
| Diagnostic ImagingAlso: Medical ImagingUndergo imaging scans | Procedure or surgery | Treatment (gemcitabine, leflunomide) |
| GemcitabineAlso: dFdC, dFdCyd, DifluorodeoxycytidineGiven IV | Drug | Treatment (gemcitabine, leflunomide) |
| LeflunomideAlso: Arava, SU101Given PO | Drug | Treatment (gemcitabine, leflunomide) |
| Magnetic Resonance ImagingAlso: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging ScanUndergo MRI | Procedure or surgery | Treatment (gemcitabine, leflunomide) |
Primary outcome
Dose limiting toxicities (DLTs)
Time frame: Up to 28 days (cycle 1)
Toxicities will be graded according to Common Terminology Criteria for Adverse Events version 5.0.
Incidence of adverse events
Time frame: Up to 30 days after completion of study treatment
Toxicities will be graded according to Common Terminology Criteria for Adverse Events version 5.0.
4 secondary outcomes
Progression-free survival (PFS)
Time frame: 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)
Time frame: 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)
Time frame: Up to 1 year after completion of study treatment
Change in quality of life (QOL)
Time frame: Baseline to 1 year after completion of study treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Vincent Chung principal investigator
City of Hope Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Biospecimen Collection, Cholestyramine and Computed Tomography in people with Advanced Pancreatic Adenocarcinoma and Stage III Pancreatic Cancer AJCC v8, run by City of Hope Medical Center 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 20 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 20 Oct 2026. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicities (DLTs) (time frame: Up to 28 days (cycle 1)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Oct 2026.