Leflunomide in Previously Treated Metastatic Triple Negative Cancers

  • End date
    Oct 16, 2025
  • participants needed
  • sponsor
    Joseph Sparano
Updated on 16 June 2022
breast cancer
triple negative breast cancer
progesterone receptor
stage iv breast cancer
estrogen receptor


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. 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.

Condition Breast Neoplasms, Breast Diseases, Metastatic Triple Negative Breast Cancer
Treatment leflunomide
Clinical Study IdentifierNCT03709446
SponsorJoseph Sparano
Last Modified on16 June 2022


Yes No Not Sure

Inclusion Criteria

Women with histologically confirmed ER ≤ 10% and or PR ≤ 10% TNBC on the pre-trial metastatic biopsy
Age ≥ 18
≤ 3 prior chemotherapies for metastatic disease
Prior immunotherapy is permitted and does not count as chemotherapy
The use denosumab or zoledronic is permitted
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)
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
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)
following completion of therapy. Should a woman become pregnant or suspect she
Ability to understand and the willingness to sign a written informed consent
is pregnant while participating in this study, she should inform her treating
physician immediately

Exclusion Criteria

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
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
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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note