Domatinostat With Sirolimus for Relapsed, Refractory Sarcoma and Osteosarcoma

Open-Label, Cohort-Sequential Dose-Escalation and Dose-Confirmation Phase 1/2 Clinical Trial to Evaluate the Safety and Efficacy of Domatinostat in Combination With Sirolimus in Adolescents and Adults With Relapsed, Refractory Sarcoma and Osteosarcoma

Status

Recruiting

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT07725380

Enrollment

Registered

2026-07-24

Start date

2026-07-15

Completion date

2031-08-01

Last updated

2026-09-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Osteosarcoma, Sarcoma

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.

Interventions

DRUGDomatinostat

Tablet

DRUGSirolimus

Tablet

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

12 Years to 40 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Phase 1: Maximum Tolerated Dose (MTD)	28 days	For the phase 1 portion, a standard 3+3 design will be used to determine the MTD and/or RP2D for the Phase 2 portion of this study.
Phase 2: Arm A Event Free Surival	12 months	Event free survival (EFS) is defined as the duration of time from start of treatment to time of disease progression, secondary malignancy, or death, whichever occurs first.
Phase 2: Arm B Event Free Surival	4 months	Event free survival (EFS) is defined as the duration of time from start of treatment to time of disease progression, secondary malignancy, or death, whichever occurs first.

Secondary

Measure	Time frame	Description
Phase 2: Overall Survival	Up to 5 years	Overall Survival (OS) of phase 2 participants.

Countries

United States

Contacts

CONTACTJessica Crimella

Jessica.Crimella@moffitt.org813-745-6250

PRINCIPAL_INVESTIGATORAmy Armstrong, MD

Washington University School of Medicine

PRINCIPAL_INVESTIGATORJonathan Metts, MD

Moffitt Cancer Center

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Sep 4, 2026