Leflunomide in Previously Treated Metastatic Triple Negative Cancers

STATUS

Recruiting
End date

Oct 16, 2025
participants needed

54
sponsor

Joseph Sparano

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Updated on 16 June 2022

See if I qualify

cancer

estrogen

breast cancer

progesterone

metastasis

triple negative breast cancer

progesterone receptor

stage iv breast cancer

erbb2

estrogen receptor

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. 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.

Details

Condition	Breast Neoplasms, Breast Diseases, Metastatic Triple Negative Breast Cancer
Treatment	leflunomide
Clinical Study Identifier	NCT03709446
Sponsor	Joseph Sparano
Last Modified on	16 June 2022

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Eligibility		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)
	AST (SGOT)/ALT (SPGT) ≤ 2 x 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

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Leflunomide in Previously Treated Metastatic Triple Negative Cancers