Domatinostat With Sirolimus for Relapsed, Refractory Sarcoma and Osteosarcoma

September 1, 2026 updated by: H. Lee Moffitt Cancer Center and Research Institute

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

74

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
        • Principal Investigator:
          • Jonathan Metts, MD
        • Sub-Investigator:
          • Andrew Brohl, MD
        • Sub-Investigator:
          • Mihaela Druta, MD
        • Sub-Investigator:
          • Mauricio Silva Almeida Ribeiro, MD
        • Sub-Investigator:
          • Isabel Canizares, APRN
        • Sub-Investigator:
          • Desiree Morales, APRN
        • Sub-Investigator:
          • Anya Ibern, APRN
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Not yet recruiting
        • Washington University in St. Louis
        • Principal Investigator:
          • Amy Armstrong, MD
    • New York
      • The Bronx, New York, United States, 10467
        • Not yet recruiting
        • Montefiore Medical Center
        • Principal Investigator:
          • Alice Lee, MD
    • Ohio
      • Columbus, Ohio, United States, 43205
        • Recruiting
        • Nationwide Children's Hospital
        • Principal Investigator:
          • Bhuvana Setty, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Domatinostat
Tablet
Drug: Sirolimus
Tablet
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.
Drug: Domatinostat
Tablet
Drug: Sirolimus
Tablet
Experimental: Phase 2 Arm B (Measurable Osteosarcoma)
Patients with unresectable measurable relapsed/refractory osteosarcoma will receive domatinostat plus sirolimus at the RP2D.
Drug: Domatinostat
Tablet
Drug: Sirolimus
Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1: Maximum Tolerated Dose (MTD)
Time Frame: 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.
28 days
Phase 2: Arm A Event Free Surival
Time Frame: 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.
12 months
Phase 2: Arm B Event Free Surival
Time Frame: 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.
4 months

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

National Pediatric Cancer Foundation
Healx USA, Inc

Investigators

  • Principal Investigator: Jonathan Metts, MD, Moffitt Cancer Center
  • Principal Investigator: Amy Armstrong, MD, Washington University School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 15, 2026

Primary Completion (Estimated)

August 1, 2031

Study Completion (Estimated)

August 1, 2031

Study Registration Dates

First Submitted

July 21, 2026

First Submitted That Met QC Criteria

July 21, 2026

First Posted (Actual)

July 24, 2026

Study Record Updates

Last Update Posted (Actual)

September 3, 2026

Last Update Submitted That Met QC Criteria

September 1, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCC-23906

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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