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Purpose

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

Eligibility

Eligible Ages
Between 12 Years and 40 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

Moffitt Cancer Center
Tampa, Florida 33612

More Details

Status
Recruiting
Sponsor
H. Lee Moffitt Cancer Center and Research Institute

Study Contact

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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.