Leflunomide in Previously Treated Metastatic Triple Negative Cancers
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|ClinicalTrials.gov Identifier: NCT03709446|
Recruitment Status : Recruiting
First Posted : October 17, 2018
Last Update Posted : December 3, 2019
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 or disease||Intervention/treatment||Phase|
|Breast Neoplasms Breast Diseases Metastatic Triple Negative Breast Cancer||Drug: Leflunomide||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||54 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Trial of Leflunomide in Women With Previously Treated Metastatic Triple Negative Cancers|
|Actual Study Start Date :||April 16, 2019|
|Estimated Primary Completion Date :||October 20, 2021|
|Estimated Study Completion Date :||October 20, 2021|
Women with metastatic triple negative breast cancer. Leflunomide tablet orally daily
Single agent leflunomide
Other Name: Arava
- Maximum Tolerated Dose (MTD) [ Time Frame: 3 months ]3+3 escalation schema. treated at each dose level until Dose-limiting Toxicity (DLT) (defined as any grade 3 or higher toxicity seen during the first cycle of leflunomide). If 2/3 patients experience a DLT, one dose level will be defined as the MTD. If 1/3 experiences a DLT, three additional patients will be enrolled. If ≤ 2/6 patients experience a DLT, the next cohort of 3 patients will be treated with 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
- Clinical Benefit Rate (CBR) [ Time Frame: 6 months ]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 [ Time Frame: 3 years ]Number of side effects using NCI CTCAE v.4.03
- Objective Response Rate [ Time Frame: 3 years ]Objective Response Rate (proportion of patients with the best overall response of CR or PR) in those who have measurable disease by RECIST
- Progression-free survival (PFS) [ Time Frame: 3 years ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03709446
|Contact: Charles Shapiro, MDemail@example.com|
|Contact: Sara Siller, RN||212-824-7396|
|United States, New York|
|Icahn School of Medicine at Mount Sinai||Recruiting|
|New York, New York, United States, 10029|
|Contact: Charles Shapiro, MD 212-241-3131 firstname.lastname@example.org|
|Contact: Sara Siller, RN 212-824-7396|
|Principal Investigator:||Charles Shapiro, MD||Icahn School of Medicine at Mount Sinai|