Clinical trial NCT04997993: Leflunomide in Patients With PTEN-Altered Advanced Solid Malignancies
Official title: A Phase IA/IB Trial of Leflunomide in Patients With PTEN-Altered Advanced Solid Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: PTEN-null Advanced Solid Tumors
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2021-08-10
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Leflunomide in patients with PTEN-null advanced solid tumors. Objectives are to determine the safety and tolerability and the MTD of leflunomide in patients with PTEN-null advanced solid malignancies and to assess preliminary evidence of clinical activity of leflunomide in patients with PTEN-null advanced solid malignancies.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18
* 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
* Patients must have measurable disease per RECIST 1.1 criteria (Appendix C).
* 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 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.
* ≥ 4 weeks from last systemic therapy, surgery or radiation.
* 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 within institutional upper limit of normal. (≤ ULN)
  * AST (SGOT)/ALT (SPGT) ≤ ULN
  * GFR (Cockroft-Gault) ≥ 50 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
* Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Number of participants with Dose-limiting toxicities
timeFrame: 1 month
measure: Number of Dose-limiting toxicities
timeFrame: 1 month
Secondary outcomes:
measure: Maximum tolerated dose
timeFrame: 2 years
measure: Overall Response Rate
timeFrame: 2 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Deborah Doroshow, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: