Recruiting

Phase 1

Phase 2

Domatinostat & SirolimusDomatinostat With Sirolimus for Relapsed, Refractory Sarcoma and Osteosarcoma

Sponsor:

H. Lee Moffitt Cancer Center and Research Institute

Code:

NCT07725380

Conditions

Sarcoma

Osteosarcoma

Eligibility Criteria

Sex: All

Age: 12 - 40

Healthy Volunteers: Not accepted

Interventions

Domatinostat

Sirolimus

Study Details

Brief summary:

This is a multicenter, open-label, Phase 1/2 study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of domatinostat in combination with sirolimus in adolescents and adults with relapsed or refractory sarcoma and osteosarcoma.

Conditions

Sarcoma

Osteosarcoma

Study ID

NCT07725380

Start date

Jul 15, 2026

Status verified date

Sep, 2026

Completion date

Aug, 2031

Anticipated

Primary completion date

Aug, 2031

Anticipated

Eligibility Criteria

Sex: All

Age: 12 - 40

Healthy Volunteers: Not accepted

Inclusion Criteria:

Age ≥12 and ≤40 years.
Histologically confirmed relapsed or refractory sarcoma (Phase 1) or osteosarcoma (Phase 2).
At least one prior standard systemic therapy regimen.
Not candidates for available therapies known to provide survival benefit.
Karnofsky/Lansky performance score ≥60.
Life expectancy ≥16 weeks.
Adequate organ function: ANC ≥1,000/mcL, Platelets ≥100,000/uL, Hemoglobin ≥8 g/dL, Adequate hepatic and renal function.
Ability to swallow tablets.
Negative pregnancy test for females of childbearing potential.
Agreement to use effective contraception.
Ability to provide informed consent/assent.

Exclusion Criteria:

Receiving another investigational agent.
Receiving concurrent anticancer therapy.
Known hypersensitivity to domatinostat or sirolimus.
Bone marrow-only disease.
CNS metastatic disease.
Major surgery within 2 weeks prior to treatment.
Active malignancy within the previous 3 years (with protocol-specified exceptions).
History of solid organ transplantation.
Significant recent cardiac disease.
Concurrent prohibited CYP3A4/P-gp interacting medications.
Uncontrolled infection or other serious uncontrolled illness.
Pregnancy or breastfeeding.
HIV infection on antiretroviral therapy.
Weight <40 kg.
Inability to comply with study requirements.

Study Design

Enrollment

74 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase 1 Dose Escalation Cohort

Participants with relapsed or refractory sarcoma will receive domatinostat plus sirolimus. Domatinostat dose levels will be escalated to determine the MTD and/or RP2D.

experimental: Phase 2 Arm A (Surgical Complete Remission Osteosarcoma)

Patients with relapsed/refractory osteosarcoma who achieve complete surgical remission before enrollment will receive domatinostat plus sirolimus at the RP2D.

experimental: Phase 2 Arm B (Measurable Osteosarcoma)

Patients with unresectable measurable relapsed/refractory osteosarcoma will receive domatinostat plus sirolimus at the RP2D.

Interventions

Domatinostat

Tablet

Sirolimus

Tablet

Primary outcome measure

Phase 1: Maximum Tolerated Dose (MTD) [ Time Frame: 28 days ]
Phase 2: Arm A Event Free Surival [ Time Frame: 12 months ]
Phase 2: Arm B Event Free Surival [ Time Frame: 4 months ]

Central Contacts and Locations

Central contacts

Jessica Crimella

813-745-6250 Jessica.Crimella@moffitt.org

Locations

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

Principal Investigator:

Jonathan Metts, MD

Nationwide Children's Hospital

Recruiting

Columbus, Ohio, United States, 43205

Principal Investigator:

Bhuvana Setty, MD

More Information

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Last update posted

Sep 3, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by H. Lee Moffitt Cancer Center and Research Institute on 2026-09-03.