Tegavivint With Gemcitabine in Patients With Relapsed or Refractory Osteosarcoma

NCT07144254 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00008647
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Osteosarcoma Recurrent; Osteosarcoma in Children; Relapsed Osteosarcoma; Refractory Osteosarcoma

Keywords

Tegavivint; TBL1 inhibitor; Gemcitabine; Osteosarcoma

Outcome Measures

Primary Outcomes (1)

• 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)

  upto day 21

Secondary Outcomes (3)

• Disease control (DC)

  upto 4 months

• Progression-Free Survival (PFS)

  End of study (upto 3 years)

• Overall Survival (OS)

  End of study (upto 3 )

Study Arms (1)

Tegavivint with Gemcitabine

EXPERIMENTAL

Subjects can receive treatment with tegavivint and gemcitabine for up to 17 cycles (1 cycle = 21 days). Treatment will be discontinued if there is progressive disease or toxicity requiring treatment discontinuation Dose Escalation: Dose level 0: Tegavivint = 3(mg/kg) and Gemcitabine 1000 (mg/m2) Dose level 1: Tegavivint = 5(mg/kg) and Gemcitabine 1000 (mg/m2) Dose level 2: Tegavivint = 6.5(mg/kg) and Gemcitabine 1000 (mg/m2)

Drug: Tegavivint; Drug: Gemcitabine

Interventions

Tegavivint DRUG

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.

Tegavivint with Gemcitabine

Gemcitabine DRUG

Gemcitabine will be administered first, intravenously (IV) over 60 minutes, on days 1 and 8 at a fixed dose of 1000 mg/m2

Tegavivint with Gemcitabine

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 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.
• Performance Level: Participants must have a Lansky (≤ 16 years) or Karnofsky (\> 16 years) score of ≥ 60, or Eastern Cooperative Oncology Group (ECOG) ≤ 2 Note: Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory to assess the performance score.
• Prior Therapy: Participants must have fully recovered from the clinically significant acute effects of all prior anti-cancer chemotherapy, immunotherapy, surgery, or radiation therapy before enrollment.
• Myelosuppressive chemotherapy: ≥ 14 days after the last dose.
• Hematopoietic growth factors: ≥ 14 days after a long-acting growth factor (e.g., pegfilgrastim) or ≥ 7 days for a short-acting growth factor. For agents with known delayed adverse events, extend recovery period accordingly.
• Biologic (anti-neoplastic) agent: ≥ 7 days after the last dose. Extend period if adverse events occur beyond 7 days.
• Cellular therapy: ≥ 21 days since last dose (e.g., modified T cells, gamma-delta T cells, natural killer (NK) cells, dendritic cells) with recovery from associated toxicities.
• Interleukins, interferons, and cytokines (excluding hematopoietic growth factors): ≥ 21 days since last dose.
• Antibodies: 7 days or 3 half-lives (whichever is longer), up to 30 days. Toxicity must be resolved to Grade ≤ 1.
• Radiation therapy (XRT):

You may not qualify if:

• 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
• Concomitant Medications:
• Investigational Drugs: Subjects who are currently receiving another investigational drug are not eligible.
• Anti-cancer Agents: Subjects who are currently receiving other anti-cancer agents are not eligible.
• CYP3A4/5 Agents: Patients currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoided from 14 days before the 1st dose of tegavivint to the end of the study. See Appendix II for a list of agents.
• Bisphosphonates: Patients receiving bisphosphonates within 4 Weeks of study enrollment are not eligible.
• Denosumab: Patients who have received denosumab within 180 days prior to study enrollment are not eligible
• Infection: Subjects who have an active, uncontrolled infection.
• Subjects who have received prior solid organ or allogeneic stem cell transplantation.
• Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
• Patients with a known metabolic bone disease (ex: hyperparathyroidism, Paget's disease, osteomalacia).
• Patients with a disorder associated with abnormal bone metabolism.

Sponsors & Collaborators

• Emory University: lead
• Iterion Therapeutics: collaborator

Study Sites (1)

Arthur M. Blank Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Osteosarcoma

Interventions

Gemcitabine

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Thomas Cash, MD, MSc

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kate Glasscox, BSN, RN

CONTACT

404-785-0002; aflacdevtreferral@choa.org

Lauren Johnson

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 20, 2025
• First Posted: August 27, 2025
• Study Start: January 22, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: March 2, 2026

Record last verified: 2026-02

Locations

US (1)