PTEN-Altered Advanced Solid Tumors and HER2 Negative Breast CancerPhase 1NCT04997993
Leflunomide in Patients With PTEN-Altered Advanced Solid Malignancies and HER2 Negative Breast Cancer
A Phase 1 study testing Leflunomide in people with PTEN-Altered Advanced Solid Tumors and HER2 Negative Breast Cancer, run by Deborah Doroshow at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- PTEN-Altered Advanced Solid Tumors and HER2 Negative Breast Cancer
- What is being tested?
- Leflunomide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Dec 2023to Jul 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
- 2 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
- Absolute neutrophil count ≥ 1,000/mcL
- Platelets ≥ 100,000/mcl
- Total bilirubin ≤ 1.5 x ULN (or direct bilirubin, if patient has Gilbert's disease)
- AST (SGOT)/ALT (SPGT) ≤ 3xULN
- GFR (Cockroft-Gault) ≥ 40 mL/min/1.73m2
- Negative serum or urine pregnancy test within 3 days prior to C1D1 of leflunomide therapy.
- 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 following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately and will immediately be taken off study therapy.
- Additionally, all women of child bearing potential must begin an accelerated elimination protocol upon drug discontinuation for any reason, unless they agree to continue taking appropriate contraception for up to 2 years from study drug discontinuation.
- Patients who do not take the accelerated elimination protocol will have to remain on contraception for two years.
- Recommended methods of birth control are: The consistent use of an approved hormonal contraception such as an intrauterine device (IUD), birth control pills, double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), sexual abstinence (no sexual intercourse) or sterilization.
- 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).
- Ability to understand and the willingness to sign a written informed consent
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Natalie Lucas, DNP contact
United States1 site, 1 recruiting
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Deborah Doroshow, MD, PhD
About this study
Official title: A Phase IA/IB Trial of Leflunomide in Patients With PTEN-Altered Advanced Solid Malignancies and HER2 Negative Breast Cancer
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.
- Being tested
- Leflunomide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LeflunomideDrug
Leflunomide, 20-50mg PO daily
| Study group | Role | What they receive |
|---|---|---|
| Leflunomide | Experimental | Leflunomide, 20-50mg PO daily Receives: Drug: Leflunomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 1 month
Secondary outcomes (2)
Maximum tolerated dose
A standard 3+3 design is used to define the MTD. Dose level 0 will only be utilized in the presence of ≥2/6 DLTs in dose level 1 or for a dose reduction if a patient does not tolerate dose level one. Standard dosing for rheumatoid arthritis is 100mg daily for 3 days loading dose followed by 20mg daily maintenance dose, which can be reduced to 10mg in the event of intolerance.
Measured: 2 years
Overall Response Rate
Overall Response Rate for dose expansion cohort. Overall response rate is defined as the proportion of patients achieving a best response of complete response or partial response using RECIST v1.1
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2021
- Study start13 Dec 2023
- Primary completionJul 2027 (estimated)
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PTEN-Altered Advanced Solid Tumors and HER2 Negative Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Deborah Doroshow
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Deborah Doroshow, Icahn School of Medicine at Mount Sinai
- Investigators
- Deborah Doroshow, MD, PhD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04997993
- Sponsor's protocol ID
- GCO 20-2528
- Status last verified
- Jun 2026
- First submitted
- 2 Aug 2021
- Last updated
- 15 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There is not a plan to make IPD available
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IA/IB Trial of Leflunomide in Patients With PTEN-Altered Advanced Solid Malignancies and HER2 Negative Breast Cancer
- ClinicalTrials.gov ID
- NCT04997993
- Acronym / sponsor ID
- GCO 20-2528
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 23 participants (estimated)
- Lead sponsor
- Deborah DoroshowUniversity, hospital or other
- Study start
- 13 Dec 2023 (actual)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Jul 2028 (estimated)
- First posted
- 10 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Leflunomide | Experimental | Drug: LeflunomideLeflunomide, 20-50mg PO daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LeflunomideLeflunomide, 20-50mg PO daily | Drug | Leflunomide |
Primary outcome
Number of participants with Dose-limiting toxicities
Time frame: 1 month
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
Number of Dose-limiting toxicities
Time frame: 1 month
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
2 secondary outcomes
Maximum tolerated dose
Time frame: 2 years
Overall Response Rate
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2026.
- Individual participant dataSharing planned: No. There is not a plan to make IPD available
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Natalie Lucas, DNP contact
Deborah Doroshow, MD, PhD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Leflunomide in people with PTEN-Altered Advanced Solid Tumors and HER2 Negative Breast Cancer, run by Deborah Doroshow at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Deborah Doroshow, MD, PhD ((212) 241-5615, deborah.doroshow@mssm.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with Dose-limiting toxicities (time frame: 1 month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2026.