Osteosarcoma RecurrentPhase 1NCT07144254
Tegavivint With Gemcitabine in Patients With Relapsed or Refractory Osteosarcoma
A Phase 1 study testing Tegavivint and Gemcitabine in people with Osteosarcoma Recurrent and Osteosarcoma in Children, run by Emory University at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 1 year to 30 years
- Conditions the study is for
- Osteosarcoma Recurrent, Osteosarcoma in Children, Relapsed Osteosarcoma
- What is being tested?
- Tegavivint and Gemcitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesUnited States
- Study dates
- 22 Jan 2026to May 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
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- -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):
- 14 days after local palliative XRT (small port)
- 150 days after radiation to ≥ 50% of pelvis or bone marrow
- 6 weeks after substantial bone marrow radiation
- Prior use of Nucleoside Analogue (Gemcitabine): Allowed. Investigational agents not otherwise specified: ≥ 30 days since last dose. Surgery: ≥ 2 weeks since last major surgery, including pulmonary metastasectomy (central line placement and core/small open biopsies are excluded)
- Organ Function Requirements:
- Adequate Bone Marrow Function Defined As:
- Peripheral absolute neutrophil count (ANC) ≥ 750/mm3 (0.75x109/L)
- Platelet count ≥ 75,000/mm3 (75x109/L)
- Adequate Renal Function Defined As: Creatinine clearance or radioisotope GFR ≥ 70 ml/min/1.73 m2
- Adequate Liver Function Defined As:
- Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x the upper limit of normal (ULN) for age
- ALT ≤ 5 x the ULN
- Adequate Pulmonary Function Defined As: No dyspnea at rest, no exercise intolerance, and no oxygen requirement (pulse oximetry > 93% on room air).
- Adequate Cardiac Function Defined As: QTc ≤ 470 ms using Fridericia formula
Who cannot join
- 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.
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- 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.
- Patients with ≥ 2 grade hypocalcemia that is not corrected with oral calcium supplementation.
- Patients with vitamin D < 20 ng/mL will require supplementation or will otherwise be excluded. Patients must agree to take vitamin D +/- calcium supplements (if necessary) according to institutional or published guidelines. Additional calcium supplementation is not required if adequate dietary intake can be ascertained.
- Patients who have previously received tegavivint are not eligible.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Melissa Schink contact
United States2 sites, 2 recruiting
- Recruiting
Arthur M. Blank Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Thomas Cash, MD, aflacdevtreferral@choa.org
Thomas Cash, MD
- Recruiting
Texas Children's
Houston, Texas, 77030
Stephanie Fetzko, MD, 832-824-6895), slfetzko@texaschildrens.org/
Kathleen McCarthy, 832-824-4804)., ksmccart@texaschildrens.org/
About this study
Official title: Study of Tegavivint, a Transducin Beta-like Protein 1 (TBL1) Inhibitor, With Gemcitabine in Patients With Relapsed or Refractory Osteosarcoma
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.
Read the detailed 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.
Tegavivint showed potent anti-tumor activity in OS cell lines and mouse models, inhibiting tumor growth and metastasis, including activity against chemoresistant and cancer stem-like cells.
Recent clinical data shows:
Adults: In a Phase 1/2a trial (NCT03459469) with 24 patients, tegavivint at 5 mg/kg (3 weeks on/1 week off) was well tolerated with no dose-limiting toxicities. Most side effects were mild (fatigue, nausea, headache), and serious toxicities common to other Wnt inhibitors were not seen. Tumor shrinkage (>50%) occurred in five patients, with others achieving prolonged stable disease.
Pediatrics: In an ongoing COG Phase 1/2 trial (NCT04851119), tegavivint was tested in 10 patients at 5 and 6.5 mg/kg. No DLTs were observed, and the recommended dose was set at 6.5 mg/kg. Most side effects were grade 1-2; grade ≥3 events were infrequent.
- Conditions
- Osteosarcoma Recurrent, Osteosarcoma in Children, Relapsed Osteosarcoma, Refractory Osteosarcoma
- Being tested
- Tegavivint, Gemcitabine
- Keywords
- Tegavivint, TBL1 inhibitor, Gemcitabine, Osteosarcoma
- Medical subject headings
- Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TegavivintDrug
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.
GemcitabineDrug
Gemcitabine will be administered first, intravenously (IV) over 60 minutes, on days 1 and 8 at a fixed dose of 1000 mg/m2
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: Tegavivint; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: upto day 21
Secondary outcomes (3)
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
Measured: upto 4 months
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
Measured: End of study (upto 3 years)
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
Measured: End of study (upto 3 )
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2025
- Study start22 Jan 2026
- Primary completionMay 2028 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteosarcoma RecurrentStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Iterion Therapeutics
- Responsible party
- Principal investigator, William T Cash, Emory University
- Investigators
- Thomas Cash, MD, MSc, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07144254
- Sponsor's protocol ID
- STUDY00008647
- Status last verified
- Oct 2026
- First submitted
- 20 Aug 2025
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Tegavivint, a Transducin Beta-like Protein 1 (TBL1) Inhibitor, With Gemcitabine in Patients With Relapsed or Refractory Osteosarcoma
- ClinicalTrials.gov ID
- NCT07144254
- Acronym / sponsor ID
- STUDY00008647
- Conditions
- Osteosarcoma Recurrent, Osteosarcoma in Children, Relapsed Osteosarcoma, Refractory Osteosarcoma
- Keywords
- Tegavivint, TBL1 inhibitor, Gemcitabine, Osteosarcoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Iterion Therapeutics
- Study start
- 22 Jan 2026 (actual)
- Primary completion
- May 2028 (estimated)
- Study completion
- May 2028 (estimated)
- First posted
- 27 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Tegavivint showed potent anti-tumor activity in OS cell lines and mouse models, inhibiting tumor growth and metastasis, including activity against chemoresistant and cancer stem-like cells.
Recent clinical data shows:
Adults: In a Phase 1/2a trial (NCT03459469) with 24 patients, tegavivint at 5 mg/kg (3 weeks on/1 week off) was well tolerated with no dose-limiting toxicities. Most side effects were mild (fatigue, nausea, headache), and serious toxicities common to other Wnt inhibitors were not seen. Tumor shrinkage (>50%) occurred in five patients, with others achieving prolonged stable disease.
Pediatrics: In an ongoing COG Phase 1/2 trial (NCT04851119), tegavivint was tested in 10 patients at 5 and 6.5 mg/kg. No DLTs were observed, and the recommended dose was set at 6.5 mg/kg. Most side effects were grade 1-2; grade ≥3 events were infrequent.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tegavivint with Gemcitabine | Experimental | Drug: Tegavivint, Drug: GemcitabineSubjects 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) |
Who may qualify
- Ages
- 1 year to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (29 listed)
- 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
- 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.
Key exclusion criteria (18 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TegavivintTegavivint 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. | Drug | Tegavivint with Gemcitabine |
| GemcitabineGemcitabine will be administered first, intravenously (IV) over 60 minutes, on days 1 and 8 at a fixed dose of 1000 mg/m2 | Drug | Tegavivint with Gemcitabine |
Primary outcome
Maximum dose tolerated
Time frame: upto day 21
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)
3 secondary outcomes
Disease control (DC)
Time frame: upto 4 months
Progression-Free Survival (PFS)
Time frame: End of study (upto 3 years)
Overall Survival (OS)
Time frame: End of study (upto 3 )
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Melissa Schink contact
Thomas Cash, MD, MSc principal investigator
Emory University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tegavivint and Gemcitabine in people with Osteosarcoma Recurrent and Osteosarcoma in Children, run by Emory University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kate Glasscox, BSN, RN (404-785-0002, aflacdevtreferral@choa.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum dose tolerated (time frame: upto day 21). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.