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Breast NeoplasmsPhase 1/2NCT03709446

Leflunomide in Previously Treated Metastatic Triple Negative Cancers

A Phase 1/2 study testing Leflunomide in people with Breast Neoplasms and Breast Diseases, run by Joseph Sparano at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Triple negative breast cancer (TNBC) represents about 15% of breast cancers and is characterized by the lack of expression of estrogen receptor (ER), progesterone receptor (PR), and HER-2 non-amplification. Women with TNBC tend to be younger, African American, and BRCA-1 germline carriers. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Leflunomide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
3 sitesUnited States
Study dates
16 Apr 2019to 27 Nov 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Women with histologically confirmed HER2-negative metastatic and/or locally advanced, inoperable breast cancer on a prior biopsy performed as a component of standard of care. The biopsy site may include the primary tumor, regional lymph node, or metastatic site if accessible to biopsy.
  • Age ≥ 18.
  • Prior treatment for metastatic breast cancer:
  • ≤ 3 prior chemotherapies for metastatic disease and up to 2 prior antibody drug conjugate regimens (eg, sacitizumab govitecan, trastuzumab deruxtecan). Patients with ER-positive breast cancer (ER>10%) must have had progressive disease after at least 1 prior line of CKD4/6 inhibitor, and also a PIK3CA inhibitor if known to have a somatic PIK3CA activating mutation (by tumor or ctDNA assay) sensitive to the PIK3CA inhibitor alpelisib.
  • Prior immunotherapy is permitted and does not count as chemotherapy.
  • The use denosumab or zoledronic is permitted.
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  • History of previously treated brain metastases with ≥ 4 weeks after definitive surgery and gamma knife/whole brain radiation and not taking steroids.
  • ≥ 4 weeks from last oral or IV chemotherapy, small molecule inhibitor, a biologic agent, surgery or radiation.
  • Performance status 0-2.
  • Adequate organ and marrow function as defined below:
  • leukocytes ≥ 3,000/mcL
  • Absolute neutrophil count ≥ 1,000/mcL
  • platelets ≥ 100,000/mcl
  • total bilirubin within institutional upper limit of normal. (≤ ULN)
  • AST (SGOT)/ALT (SPGT) ≤ 3 x ULN (3xULN if liver mets)
  • Creatinine ≤ ULN
  • A negative serum or urine pregnancy test within 3 days of receiving Day 1 Cycle 1 of leflunomide.
  • Women of child-bearing potential and men must agree to use adequate contraception before study entry, for the duration of study participation and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Recommended methods of birth control are: The consistent use of an approved hormonal contraception such as an intrauterine device (IUD), Double barrier methods (Diaphragm with spermicidal gel or condoms with contraceptive foam), Sexual abstinence (no sexual intercourse) or Sterilization. The use of hormonal forms of birth control is controversial in TNBC and as such women enrolled in the trial are permitted to use birth control pills or depot Provera, only after a documented discussion by the treating physician as too the uncertain risks of hormonal birth control methods in the TNBC population. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 months).
  • Ability to understand and the willingness to sign a written informed consent.

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within ≥ 2 weeks before entering the study or those who have not recovered from adverse events due to agents administered more than ≥ 4 weeks earlier.
  • Patients may not be receiving any other investigational agents.
  • The known history human immunodeficiency virus, acute and chronic Hepatitis B or C, or acute or previously treated tuberculosis.
  • Patients with untreated brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to leflunomide or teriflunomide.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Mt Sinai Chelesa

    New York, New York, 10011

  • Mt Sinai West

    New York, New York, 10019

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

Other trials in United States

About this study

Official title: A Phase I/II Trial of Leflunomide in Women With Previously Treated Metastatic Triple Negative Cancers

Triple negative breast cancer (TNBC) represents about 15% of breast cancers and is characterized by the lack of expression of estrogen receptor (ER), progesterone receptor (PR), and HER-2 non-amplification. Women with TNBC tend to be younger, African American, and BRCA-1 germline carriers. The hallmark of this subtype is early metastatic recurrences with a peak frequency 1-2 years. 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 cancer.

The primary objective of the phase I part of this study is to determine the safety, tolerability and maximum tolerated dose of leflunomide in women with previously treated TNBC (or ER+ , HER2-neg MBC in Phase I). The primary objective of the phase 2 part of this study is to determine the efficacy of leflunomide in patients with TNBC.

Leflunomide, which will be taken daily by mouth, is an inhibitor of dihydroorotate dehydrogenase (DHODH). This proposal will test if DHODH is a novel target for a particular subset of women with metastatic TNBC.

Being tested
Leflunomide
Keywords
Breast Neoplasms, Breast Diseases, Leflunomide, Teriflunomide, Phosphatase and tensin homolog
Medical subject headings
Breast Neoplasms, Breast Diseases, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LeflunomideDrug

    Also called Arava

    Single agent leflunomide

Study groups in NCT03709446
Study groupRoleWhat they receive
LeflunomideExperimentalWomen with HER2-negative metastatic and/or locally advanced, inoperable breast cancer. Leflunomide tablet orally daily
Receives: Drug: Leflunomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD)

    3+3 escalation schema. Patients will be enrolled in escalating cohorts of 3 patients per dose level until Dose-limiting Toxicity (DLT) (defined as any grade 3 or higher toxicity seen during the first 3-week cycle of leflunomide). If 0 of 3 patients are observed to have a DLT, the next 3 patients will be enrolled in the next higher dose level cohort. If 2/3 patients experience a DLT, escalation will stop and the previous dose will be defined as the MTD. If 1/3 experiences a DLT, three additional patients will be enrolled at the same dose level. If ≤ 2/6 patients experience a DLT, the next cohort of three patients will be treated at the next dose level. If ≥ 3/6 experience a DLT, the next lower dose level will define the MTD. If at the 50 mg dose/day if 0/3 or ≤ 2/6 patients experience a DLT, then that dose will define the MTD

    Measured: 3 months

  2. Clinical Benefit Rate (CBR)

    Response and progression to be evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST). CBR = Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) for at least 6 months duration

    Measured: 6 months

Secondary outcomes (3)

  1. Number of side effects

    Number of side effects associated with oral leflunomide using NCI CTCAE v.4.03

    Measured: 6 years

  2. Objective Response Rate

    Objective Response Rate (proportion of patients with the best overall response of CR or PR) in those who have measurable disease by RECIST

    Measured: 6 years

  3. Progression-free survival (PFS)

    PFS of women with phosphatase and tensin homolog (PTEN) wild-type and PTEN null expression breast cancers. PFS is defined as the duration of time from the start of treatment to the first occurrence of disease progression or death from any cause, whichever occurs first.

    Measured: 6 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Oct 2018
  2. Study start16 Apr 2019
  3. Primary completion27 Nov 2025
  4. Study completion27 Nov 2025

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03709446
Sponsor's protocol ID
GCO 18-1832
Status last verified
Dec 2025
First submitted
14 Oct 2018
Last updated
19 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Leflunomide in people with Breast Neoplasms and Breast Diseases, run by Joseph Sparano at 3 sites 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 7 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: finished, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) (time frame: 3 months). 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?

On the ClinicalTrials.gov record for NCT03709446.

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 19 Mar 2026; AzTrials last refreshed its copy on 2 Nov 2026.

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