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.
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
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 eligible during the dose escalation phase.
Dose Expansion: Participants with measurable or evaluable disease per RECIST and those with no evidence of disease on imaging following pulmonary metastasectomy are eligible during the dose expansion phase.
Myelosuppressive chemotherapy: ≥ 14 days after the last dose.
CNS disease: Patients with a history of intraparenchymal CNS disease (osteosarcoma) are not eligible unless they have imaging documenting stability of CNS lesions for ≥ 3 months prior to enrollment
Pregnancy or Breast-Feeding
Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
Males or females of reproductive potential are not eligible unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method
Single group
Tegavivint
DrugTegavivint 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.
Gemcitabine
DrugGemcitabine will be administered first, intravenously (IV) over 60 minutes, on days 1 and 8 at a fixed dose of 1000 mg/m2
Maximum dose tolerated
The maximum tolerated dose (MTD) of Tegavivint administered intravenously over 4 hours on days 1, 8, and 15 at the dose level assigned at study entry in combination with gemcitabine. The MTD is empirically defined as the highest dose level at which no more than one patient is experiencing a dose-limiting toxicity (DLT) and the next higher dose level has been determined to be too toxic. The MTD will be determined during Cycle 1 (each cycle is 21 days)
Disease control (DC)
The DC rate is defined as the number of patients without disease progression (complete response, partial response, or stable disease) during the first 4 months after enrollment
Progression-Free Survival (PFS)
PFS will be defined as the time from enrollment to disease relapse, disease progression, or death from any cause. Patients without an event will be censored at the time of the last disease follow-up Time to event analysis of PFS will be performed using the Kaplan-Meier method
Overall Survival (OS)
Overall survival will be defined as the time from enrollment to death from any cause Time to event analysis of OS will be performed using the Kaplan-Meier method
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Emory University
Lead sponsor
Iterion Therapeutics
Collaborator
