Domatinostat With Sirolimus for Relapsed, Refractory Sarcoma and Osteosarcoma

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

  • Sarcoma
  • Osteosarcoma

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