Leflunomide for Triple Negative Breast Cancer

Not currently recruiting at 2 trial locations

Overseen By Rita Vaccaro, RN

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Charles L Shapiro MD

Must not be taking: Investigational agents

Disqualifiers: HIV, Hepatitis B/C, untreated brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called leflunomide to determine its safety and effectiveness for women with triple negative breast cancer (TNBC), a challenging cancer with limited treatment options. Researchers aim to discover if leflunomide can benefit women who have already tried other treatments. Suitable candidates for this trial have TNBC or similar breast cancers that have spread and do not respond to standard treatments. Participants will take leflunomide in pill form daily. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that leflunomide is likely to be safe for humans?

Research has shown that leflunomide has been tested for safety in other types of cancer. One study administered it to patients with advanced solid tumors to assess their tolerance and determine the highest safe dose. This indicates that the drug undergoes careful study to ensure safety at various doses.

Leflunomide is already approved for treating rheumatoid arthritis, providing some evidence of its safety in humans. However, since its safety and effectiveness can vary with different illnesses, ongoing trials remain crucial.

The current trial is in the early stages for treating triple-negative breast cancer. At this stage, researchers focus heavily on safety and patient tolerance. While past studies suggest it might be well-tolerated, this trial will provide more specific information for this type of cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for triple negative breast cancer?

Leflunomide is unique because it targets triple negative breast cancer (TNBC) differently from current treatments, which often include chemotherapy agents like anthracyclines and taxanes. Most treatments for TNBC work by killing rapidly dividing cells, but Leflunomide has a different mechanism of action, inhibiting the growth of cancer cells by blocking a key enzyme involved in cell reproduction. Researchers are excited about Leflunomide because it offers a potentially more targeted approach, which might result in fewer side effects and improved outcomes for patients with this aggressive form of breast cancer.

What evidence suggests that leflunomide might be an effective treatment for triple negative breast cancer?

Research has shown that leflunomide, which participants in this trial will receive, might help treat triple negative breast cancer (TNBC). Leflunomide blocks an enzyme called DHODH, which may be crucial for cancer cell growth. Although still under investigation, early results suggest that targeting DHODH could slow or halt the growth of TNBC cells. While further research is necessary, this unique approach offers hope for improved outcomes in this aggressive cancer type. ^{5 6 7 8 9}

Who Is on the Research Team?

Joseph Sparano, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

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

I am taking denosumab or zoledronic.

I have had immunotherapy, but not chemotherapy.

I had brain surgery or radiation for cancer over 4 weeks ago and am not on steroids.

Exclusion Criteria

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

I do not have untreated brain metastases.

You have had allergic reactions to drugs similar to leflunomide or teriflunomide.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Determine the safety, tolerability, and maximum tolerated dose of leflunomide in women with previously treated TNBC

3 months

Regular visits for dose escalation and monitoring

Phase II Treatment

Determine the efficacy of leflunomide in patients with TNBC

6 months

Regular visits for efficacy assessment using RECIST criteria

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 years

Annual visits for long-term monitoring of side effects and progression-free survival

What Are the Treatments Tested in This Trial?

Interventions

• Leflunomide

Trial Overview 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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

Charles L Shapiro MD

Lead Sponsor

Trials

1

Recruited

50+

Joseph Sparano

Lead Sponsor

Trials

1

Recruited

50+

Published Research Related to This Trial

Leflunomide shows significant immunosuppressive effects in liver and kidney transplant recipients, allowing for reductions in conventional immunosuppressive drugs like cyclosporine and prednisone without evidence of acute rejection.

The drug was well tolerated in patients with lower serum creatinine levels, but those with higher levels experienced more side effects, highlighting the importance of monitoring serum drug levels for safe and effective dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experiences with leflunomide in solid organ transplantation. Williams, JW., Mital, D., Chong, A., et al.[2022]

Leflunomide, through its active metabolite teriflunomide, is effective in managing BK polyomavirus (BKV) infections in renal transplant recipients, with therapeutic concentrations above 40 microg/mL leading to improved clearance of the virus.

A new high-performance liquid chromatography (HPLC) method has been developed for monitoring teriflunomide levels in patients, allowing for rapid and accurate measurement to ensure effective dosing while minimizing toxicity risks.

NCBI (Pubmed)

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. Sobhani, K., Garrett, DA., Liu, DP., et al.[2021]

In a study of 32 sarcoidosis patients, leflunomide was found to be effective, with a complete or partial response in 12 out of 17 patients treated with leflunomide alone and 13 out of 15 patients receiving it alongside methotrexate.

Leflunomide was well tolerated, with only three patients experiencing nausea, and no serious adverse reactions reported, suggesting it may be a safer alternative to methotrexate for patients who cannot tolerate it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leflunomide for chronic sarcoidosis. Baughman, RP., Lower, EE.[2019]

Leflunomide treatment in a hamster-to-mouse heart transplantation model effectively prevents the formation of xenoantibodies (XAb) and chronic rejection in the first transplanted hearts, indicating its potential as an immunosuppressive agent for xenotransplantation.

The study suggests that leflunomide induces T-independent B-lymphocyte xenotolerance, as it prevents rejection of the first grafts while allowing for chronic lesions in second grafts after treatment withdrawal, highlighting its role in modulating immune responses.

NCBI (Pubmed)

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. Yan, Y., Verbeken, E., Yu, L., et al.[2019]

In a study of 7 pediatric kidney transplant patients, leflunomide effectively controlled BK virus viremia, with 67% achieving complete viral clearance, even with reduced immunosuppressive therapy.

No serious adverse effects like graft rejection or hepatotoxicity were observed, although some patients experienced mild issues like hemolytic anemia and pancreatitis, suggesting leflunomide may be a safe option for managing BK virus in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leflunomide for BKvirus: Report of Seven Kidney-Transplanted Children. Launay, M., Baudouin, V., Guillemain, R., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03709446

Leflunomide in Previously Treated Metastatic Triple ... Prognosis for metastatic TNBC is especially poor with median survival of about 1 year as compared to about 2-4 years with other types of metastatic breast ...

2. withpower.com withpower.com/trial/phase-2-breast-neoplasms-3-2019-18867

Leflunomide for Triple Negative Breast Cancer This trial is testing the safety and effectiveness of leflunomide, a daily oral medication, in women with aggressive triple negative breast cancer.

3. aging.networkofcare.org aging.networkofcare.org/riverside/CommunityResources/ClinicalTrials/Detail/NCT03709446?keyword=%22Breast%20Diseases%22

Leflunomide in Previously Treated Metastatic Triple ... Prognosis for metastatic TNBC is especially poor with median survival of about 1 year as compared to about 2-4 years with other types of metastatic breast ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11182808/

Treatment patterns and clinical outcomes in patients with ... This study evaluated treatment patterns and clinical outcomes among patients with metastatic triple-negative breast cancer (mTNBC) in real-world clinical ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7718625/

A review of current progress in triple-negative breast ... In the past 2–3 years, more positive results have emerged in the clinical research on TNBC treatment. Based on the results, several impressive drugs have been ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03709446

Leflunomide in Previously Treated Metastatic Triple ... Prognosis for metastatic TNBC is especially poor with median survival of about 1 year as compared to about 2-4 years with other types of metastatic breast ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04997993

NCT04997993 | Leflunomide in Patients With PTEN- ... Phase 1A objectives are to determine the safety, tolerability, and the MTD of leflunomide in patients with PTEN-Altered advanced solid malignancies and HER2 ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12293329/

Toxicity Profiles of Antibody–Drug Conjugates Methods: We reviewed safety data from phase 3 clinical trials in HER2-negative ... Triple-negative breast cancer (TNBC)—defined by the absence of ...

9. ema.europa.eu ema.europa.eu/en/documents/product-information/arava-epar-product-information_en.pdf

Arava, INN-leflunomide - EMA No clinical data are available on the efficacy and safety of vaccinations under leflunomide treatment. Vaccination with live attenuated vaccines is, however ...