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.
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
Drug | Synonyms | Arms |
---|
Leflunomide | | Leflunomide |
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
Name | Type | Description | Interventions |
---|
Leflunomide | Experimental | Leflunomide, 20-50mg PO daily | |
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