Clinical Trials /

Leflunomide in Patients With PTEN-null Advanced Solid Malignancies

NCT04997993

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Leflunomide in Patients With PTEN-null Advanced Solid Malignancies
  • Official Title: A Phase IA/IB Trial of Leflunomide in Patients With PTEN-null Advanced Solid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: GCO 20-2528
  • NCT ID: NCT04997993

Conditions

  • PTEN-null Advanced Solid Tumors

Interventions

DrugSynonymsArms
LeflunomideLeflunomide

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
LeflunomideExperimentalLeflunomide, 20-50mg PO daily
  • Leflunomide

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
             within 6 months 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with Dose-limiting toxicities
Time Frame:1 month
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Maximum tolerated dose
Time Frame:2 years
Safety Issue:
Description: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.
Measure:Overall Response Rate
Time Frame:2 years
Safety Issue:
Description: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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Deborah Doroshow

Last Updated

August 10, 2021