Phase 1/2 Trial to Evaluate the Safety and Efficacy of PEEL-224 in Combination With Vincristine and Temozolomide in Adolescents and Young Adults With Relapsed or Refractory Sarcomas

Recruiting now · Phase 1/Phase 2

Conditions studied: Sarcoma, Sarcoma, Ewing, Desmoplastic Small Round Cell Tumor, Refractory Sarcoma, Osteosarcoma, Rhabdomyosarcoma

In brief

This research is being done to test a new drug called PEEL-224 in combination with two commercially available drugs, Vincristine and Temozolomide, and to determine how effective this combination of drugs is at treating Ewing Sarcoma (EWS) and Desmoplastic Small Round Cell Tumor (DSRCT), as well as multiple other kinds of sarcomas. The names of the study drugs and biological agents involved in this study are: * PEEL-224 (a type of Topoisomerase 1 inhibitor) * Vincristine (A type of vinca alkaloid) * Temozolomide (A type of alkylating agent) * Pegfilgrastim or Filgrastim (types of Myeloid growth factors)

Key facts

Study ID: NCT06709495
Run by: David S Shulman, MD
People needed: 63
Starts: 2025-01-27
Expected to finish: 2029-09-01
Last updated by the study team: 2026-02-19

Who can join

Age: 12 and older, up to 49. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Patients in all cohorts must have relapsed or refractory disease after standard therapy.
Inclusion Criteria Phase 1 (only) diagnosis requirements:
Patients must have:
Evaluable or measurable disease; and
Histologic diagnosis of sarcoma
Inclusion Criteria Phase 2 (only) diagnosis requirements
EWS cohort: Patients must have:
RECIST measurable disease at study entry;
Histologic diagnosis consistent with Ewing sarcoma; and
Molecular evidence of a FET-ETS family translocation including but not limited to any of the following:
EWSR1::FLI1, EWSR1::ERG, EWSR1::ETV1, EWSR1::ETV4, EWSR1::FEV, FUS::FLI1, FUS::ERG
DSRCT cohort: Patients must have:
RECIST measurable disease at study entry;
Histologic diagnosis consistent with DSRCT; and
Molecular evidence of an EWSR1::WT1 fusion
Other sarcoma cohort: Patients must have:
RECIST evaluable or measurable disease; and
Histologic diagnosis of sarcoma. Patients with EWS or DSRCT with evaluable but not measurable disease may participate in this cohort.
Slots in this cohort will include three dedicated slots for patients with rhabdomyosarcoma, three dedicated slots for patients with osteosarcoma and three dedicated slots for patients with other translocation-associated round cell sarcomas.
Age: ≥ 12 years and ≤ 49 years.
Weight: Patients must be ≥ 40 kg.
Performance Status: Karnofsky ≥ 50% for patients >16 year of age and Lansky ≥ 50% for patients ≤ 16 years of age. (see Appendix A for definitions of Lansky and Karnofsky Performance Status).
Participants must meet the following organ and marrow function as defined below: Adequate Bone Marrow Function:
Hematologic Requirements for Subjects without Bone Marrow Involvement by
Disease:

You may not qualify if…

Patients who have received prior treatment with PEEL-224.
Patients who have had progressive disease while receiving irinotecan and temozolomide in combination will be excluded from the Phase 2 EWS and DSRCT cohorts only.
Participants who are receiving any other anti-cancer agents for this condition.
Patients receiving strong P450 CYP1A2 and CYP3A4 inhibitors and/or inducers with 14 days of the first planned dose of PEEL-224. NOTE: levofloxacin is permitted and preferred over ciprofloxacin for patients needing a fluoroquinolone.
Patients who have received a solid organ or allogeneic stem cell transplant
Pregnant participants, given that the effects of PEEL-224 on the developing human fetus are unknown.
Breastfeeding mothers, because there is an unknown risk for adverse events in nursing infants secondary to treatment of the mother with PEEL-224.
Patients with a history of allergic reactions attributed to PEGylated drugs, camptothecins, temozolomide or vincristine.
Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Where it is running

Dana-Farber Cancer Institute — Boston, Massachusetts, United States (enrolling)
Boston Children's Hospital — Boston, Massachusetts, United States
Brigham and Women's Hospital — Boston, Massachusetts, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.