Breast Cancer > Leflunomide

Leflunomide for Triple Negative Breast Cancer

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen By Joseph Sparano, MD

Age: 18+

Sex: Female

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Charles L Shapiro MD

No Placebo Group

Approved in 4 jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing the safety and effectiveness of leflunomide, a daily oral medication, in women with aggressive triple negative breast cancer. The drug aims to block a substance that helps cancer cells grow. The study focuses on women who have already tried other treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be at least 4 weeks from your last chemotherapy, small molecule inhibitor, biologic agent, surgery, or radiation before starting the trial.

What makes the drug Leflunomide unique for treating triple negative breast cancer?

Leflunomide is unique because it is primarily known as an immunosuppressive drug used for conditions like rheumatoid arthritis and organ transplantation, where it helps suppress the immune system and has antiviral properties. Its use in triple negative breast cancer is novel, as it may offer a different mechanism of action compared to traditional cancer treatments, potentially targeting cancer cells in a new way.

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Eligibility Criteria

This trial is for women with metastatic triple-negative breast cancer or ER+, HER2- negative breast cancer who have undergone previous treatments. They must be over 18, not pregnant, willing to use contraception, and have a performance status of 0-2. Participants should not have had chemotherapy or radiotherapy within the last 4 weeks and must have recovered from any prior treatment side effects.

Inclusion Criteria

Your blood and organ function tests must show certain levels within normal ranges, and you must have a negative pregnancy test before starting the study drug leflunomide.

I am 18 years old or older.

I can take care of myself and perform daily activities.

Exclusion Criteria

I do not have any severe illnesses that could interfere with the study.

I do not have untreated brain metastases.

I haven't had chemotherapy or radiotherapy in the last 2 weeks and have recovered from any side effects from treatments over 4 weeks ago.

I have a history of HIV, Hepatitis B or C, or tuberculosis.

Participant Groups

The study is testing Leflunomide's safety and effectiveness in treating metastatic TNBC. It's taken orally daily and targets DHODH, an enzyme that may play a role in this type of cancer. The trial has two phases: Phase I determines the maximum tolerated dose; Phase II assesses how well it works against TNBC.

Group I: Leflunomide Experimental Treatment 1 Intervention

Women with HER2-negative metastatic and/or locally advanced, inoperable breast cancer. Leflunomide tablet orally daily

Leflunomide is already approved in European Union, United States, United Kingdom for the following indications:

🇪🇺 Approved in European Union as Arava for:

• Rheumatoid arthritis
• Psoriatic arthritis

🇺🇸 Approved in United States as Arava for:

• Rheumatoid arthritis
• Psoriatic arthritis

🇬🇧 Approved in United Kingdom as Arava for:

• Rheumatoid arthritis
• Psoriatic arthritis

Find A Clinic Near You

Research locations nearby Select from list below to view details:

Icahn School of Medicine at Mount Sinai New York, NY

Mt Sinai Chelesa New York, NY

Mt Sinai West New York, NY

Who is running the clinical trial?

Charles L Shapiro MD Lead Sponsor

Joseph Sparano Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Experiences with leflunomide in solid organ transplantation. [2022] Leflunomide (Arava), a drug widely used for treatment of rheumatoid arthritis, has a very promising background in experimental transplantation. Its activity in experimental models of chronic rejection, its synergy with calcineurin phosphatase inhibitors, and its inhibitory effects on herpes virus replication are compelling reasons to pursue its clinical evaluation in transplantation. We report the use of this drug over the past 3 years in various clinical situations.

2. Italy pubmed.ncbi.nlm.nih.gov

Leflunomide for chronic sarcoidosis. [2019] Leflunomide (Arava) is a cytotoxic drug which has been used as a single agent or in combination with methotrexate for the treatment of rheumatoid arthritis. It appears to have less toxicity than methotrexate. The use of leflunomide for sarcoidosis patients has not been systematically evaluated.

3. England pubmed.ncbi.nlm.nih.gov

A rapid and simple high-performance liquid chromatography assay for the leflunomide metabolite, teriflunomide (A77 1726), in renal transplant recipients. [2021] Leflunomide (Arava), a drug with immunosuppressive and antiviral effects, is being used in renal transplant recipients, primarily for its action against BK polyomavirus (BKV), which affects 1% to 10% of renal transplant recipients and often causes failure of grafted kidneys. Leflunomide effects are solely due to an active metabolite, teriflunomide (formerly A77 1726). Trough blood concentrations of teriflunomide exceeding 40 microg/mL (148 micromol/L) are associated with progressive clearance of BKV. Toxic effects become increasingly apparent at higher concentrations. We have developed a rapid, simple, and robust high-performance liquid chromatography (HPLC) method for therapeutic monitoring of teriflunomide in renal transplant recipients. Sample preparation is rapid, and each HPLC separation takes about 7 minutes. Intraday and interday coefficients of variation were 1.5% or less and 5.6% or less, respectively. The method was linear to 200 microg/mL (740 micromol/L), which is well above teriflunomide concentrations that are likely to be observed.

4. Iran pubmed.ncbi.nlm.nih.gov

Leflunomide for BKvirus: Report of Seven Kidney-Transplanted Children. [2022] Leflunomide is an immunosuppressive agent commercialized for treatment of rheumatoid arthritis. Because of its immunosuppressive and possible antiviral properties, leflunomide has been evaluated in some case series of BKVAN with favorable results, mostly in adult patients. Leflunomide targeted levels are usually between 50 and 100 mg/L in kidney transplant adult patients. Data in pediatric population are scarce.

5. United States pubmed.ncbi.nlm.nih.gov

Effects of a short course of leflunomide on T-independent B-lymphocyte xenoreactivity and on susceptibility of xenografts to acute or chronic rejection. [2019] Leflunomide is a novel immunosuppressive agent with promising activity for xenotransplantation. It is not clear yet which mechanisms of action of leflunomide are responsible for that.