Study of Tegavivint, a Transducin Beta-like Protein 1 (TBL1) Inhibitor, With Gemcitabine in Patients With Relapsed or Refractory Osteosarcoma
Emory University
Summary
The goal of this clinical trial is to define the maximum tolerated dose (MTD) and/or Recommended phase 2 dose (RP2D) of Tegavivint in combination with Gemcitabine in patients with relapsed or refractory osteosarcoma (OS). The study will also investigate the toxicities of Tegavivint in combination with gemcitabine in patients with relapsed or refractory OS.
Description
Recurrent osteosarcoma (OS) has a poor prognosis, with 5-year overall survival after relapse ranging from 13% to 45%. There are currently no chemotherapy agents proven to significantly improve survival in relapsed or refractory OS, particularly in patients with unresectable disease, highlighting the need for new treatments. Tegavivint is a first-in-class small molecule that targets the Wnt/beta-catenin signaling pathway by inhibiting the TBL1-beta-catenin complex, leading to beta-catenin degradation and suppression of oncogenic transcription without affecting its normal cellular functions. T…
Eligibility
- Age range
- 1–30 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: Diagnosis: Participants must have had histologic verification of osteosarcoma at original diagnosis or relapse. * All participants with relapsed or refractory osteosarcoma are eligible, provided they received front-line treatment with a regimen that contained at least 3 of the following agents: methotrexate, doxorubicin, cisplatin, and ifosfamide -Disease Status: * Dose Escalation: Participants must have either measurable or evaluable disease per RECIST.Note: Participants with no evidence of disease on imaging (e.g., following pulmonary metastasectomy) are not eligibl…
Interventions
- DrugTegavivint
Tegavivint will be administered second, IV over 4 hours, on days 1, 8, and 15 at the dose level assigned at study entry Cycle length will be 21 days. A cycle may be repeated for a total of 17 cycles, up to a total duration of therapy of approximately 12 months.
- DrugGemcitabine
Gemcitabine will be administered first, intravenously (IV) over 60 minutes, on days 1 and 8 at a fixed dose of 1000 mg/m2
Location
- Arthur M. Blank Children's Healthcare of AtlantaAtlanta, Georgia