Neoplasms

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Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

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Teriflunomide

Leflunomide

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

Leflunomide tablet orally daily

Rita Vaccaro, RN

Joseph Sparano, MD

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.

Leflunomide in Previously Treated Metastatic Triple Negative Cancers

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

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

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

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

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

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Leflunomide in Previously Treated Metastatic Triple Negative Cancers	NCT03709446	Breast Neoplasm... Breast Diseases Metastatic Trip...	Leflunomide	18 Years -	Icahn School of Medicine at Mount Sinai
Leflunomide in Previously Treated Metastatic Triple Negative Cancers	NCT03709446	Breast Neoplasm... Breast Diseases Metastatic Trip...	Leflunomide	18 Years -	Icahn School of Medicine at Mount Sinai

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