Leflunomide in Patients With PTEN-Altered Advanced Solid Malignancies and HER2 Negative Breast Cancer

NCT04997993 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: GCO 20-2528
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Leflunomide in patients with PTEN-Altered advanced solid tumors or HER2 negative breast cancer. Phase 1A objectives are to determine the safety, tolerability, and the MTD of leflunomide in patients with PTEN-Altered advanced solid malignancies and HER2 negative breast cancer. Phase 1B objective is to assess preliminary evidence of clinical activity of leflunomide in these patient populations.

Conditions

PTEN-Altered Advanced Solid Tumors and HER2 Negative Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Number of participants with Dose-limiting toxicities

  Grade 3 or higher non-hematologic toxicity, Any death not clearly due to the underlying disease, Cases defined by Hy's law, Grade 4 neutropenia or thrombocytopenia \> 7 days, Grade 3 thrombocytopenia with clinically significant bleeding, Febrile neutropenia

  1 month

• Number of Dose-limiting toxicities

  Grade 3 or higher non-hematologic toxicity Any death not clearly due to the underlying disease Cases defined by Hy's law Grade 4 neutropenia or thrombocytopenia \> 7 days Grade 3 thrombocytopenia with clinically significant bleeding Febrile neutropenia

  1 month

Secondary Outcomes (2)

• Maximum tolerated dose

  2 years

• Overall Response Rate

  2 years

Study Arms (1)

Leflunomide

EXPERIMENTAL

Leflunomide, 20-50mg PO daily

Drug: Leflunomide

Interventions

Leflunomide DRUG

Leflunomide, 20-50mg PO daily

Leflunomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18
• A) Advanced or metastatic solid tumor with lack of PTEN expression as determined by immunohistochemistry. Lack of PTEN expression is defined as the absence of staining in the tumor (\<5%), with strong positive staining of adjacent normal endometrium or stromal cells, using the monoclonal DAKO antibody 6H2.1.9 OR
• B) Advanced or metastatic solid tumor with a deleterious somatic mutation in PTEN as determined by tissue or ctDNA testing in a CLIA laboratory and classified as deleterious in the ClinVar or COSMIC databases OR
• C) Advanced or metastatic HER2 negative breast cancer. Patients must have received ≤ 3 prior cytotoxic chemotherapies for metastatic disease (immunotherapy does not count as a line of therapy), and up to 2 prior antibody drug conjugate regimens (eg, sacituzumab govitecan, trastuzumab deruxtecan). Patients with ER-positive breast cancer (ER\>10%) are eligible if they have had progressive disease after at least 1 prior CKD4/6 inhibitor. Patients must have received alpelisib or capivasertib if eligible for either therapy or must be intolerant to or have refused such therapy.
• °Patients with known PTEN altered breast cancer may participate regardless of lines of prior therapy if they meet criteria A or B.
• Measurable disease only required for dose expansion in non-prostate ca patients
• Patients with prostate cancer without measurable disease must have evaluable disease as assessed by serum PSA.
• Patients must have progressed on, be refractory or intolerant of standard therapy for their cancer, if such a standard therapy exists.
• Patients with treated brain metastases are eligible if follow-up brain imaging at least 4 weeks after CNS directed therapy shows no evidence of progression.
• Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS directed therapy is not required and is unlikely to be required during the first cycle of therapy.
• week or five half life treatment (whichever is shorter) washout from systemic therapy, surgery, or RT. Patients with prostate cancer receiving gonadotropin-releasing hormone agonists may continue their use while on study.
• ECOG performance status 0-2.
• Patients with HIV on effective anti-retroviral therapy with an undetectable viral load are eligible for this trial.
• Adequate organ and marrow function as defined below:
• Leukocytes ≥ 3,000/mcL

You may not qualify if:

• Patients with primary CNS tumors are not eligible.
• Patients who have had chemotherapy or radiotherapy within 4 weeks before entering the study or those who have not recovered from grade ≥ 2 adverse events due to agents administered more than 4 weeks earlier. Adverse events such as alopecia, hypothyroidism, and neuropathy are allowed. Other adverse events may be allowed by permission of the principal investigator.
• Patients may not be receiving any other investigational agents.
• A known history of acute or chronic Hepatitis B or C, due to the known potential hepatotoxicity of leflunomide.
• 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.

Sponsors & Collaborators

• Deborah Doroshow: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Interventions

Leflunomide

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Deborah Doroshow, MD, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Deborah Doroshow, MD, PhD

CONTACT

(212) 241-5615; deborah.doroshow@mssm.edu

Natalie Lucas, DNP

CONTACT

natalie.lucas@mssm.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 2, 2021
• First Posted: August 10, 2021
• Study Start: December 13, 2023
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: June 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)