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

Part of paid clinical trials in Boston, Massachusetts.

Sponsor
David S Shulman, MD
Study ID
NCT06709495
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Desmoplastic Small Round Cell Tumor
  • Osteosarcoma
  • Refractory Sarcoma
  • Rhabdomyosarcoma
  • Sarcoma
  • Sarcoma, Ewing

Eligibility Criteria

Sex
ALL
Age
12 Years - 49 Years
Healthy Volunteers
Not accepted

Interventions

  • PEEL-224 — DRUG
    Topoisomerase 1 inhibitor, 200mg amber vial, via intravenous (into the vein) infusion per protocol.
  • Temozolomide — DRUG
    Alkylating agent, 5, 20, 100, 140, 180, or 250 mg capsule, taken orally per standard of care.
  • Vincristine — DRUG
    Vinca alkaloid, 1 or 2mL vials, via intravenous (into the vein) infusion per institutional policy.
  • Pegfilgrastim — BIOLOGICAL
    Myeloid growth factor administered per institutional standards.
  • Filgrastim — BIOLOGICAL
    Myeloid growth factor administered per institutional standards.

Study Details

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 Dates

Start date
Jan 27, 2025
Status verified
Feb 2026
Primary completion
Nov 1, 2028
Completion
Sep 1, 2029

Study Design

Enrollment
63 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Phase 1: Dose Escalation PEEL-224 Dose Level 0
    Up to 15 participants will be enrolled using a Bayesian design, the Continual Reassessment Method (CRM), to determine the maximum tolerated dose of PEEL-224 and starting at Dose Level 0. Transition to a lower dose level will be determined by types of dose-limiting toxicities observed per the protocol. * Baseline visit with assessments and imaging * Cycle 1 (21 day cycle): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Day 10: Myeloid growth factor (Pegfilgrastim or Filgrastim) administration 1x daily * Cycle 2 through End of Treatment (21 day cycles): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Imaging every 2 cycles until Cycle 6 and then every 3 cycles * End of study visit
  • Experimental: Phase 1: Dose Escalation PEEL-224 Dose Level -1A
    Transition to a lower dose level will be determined by types of dose-limiting toxicities observed per the protocol, otherwise establishment of the MTD/RP2D will be according to the CRM model. * Baseline visit with assessments and imaging * Cycle 1 (21 day cycle): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Day 10: Myeloid growth factor (Pegfilgrastim or Filgrastim) administration 1x daily * Cycle 2 through End of Treatment (21 day cycles): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Imaging every 2 cycles until Cycle 6 and then every 3 cycles * End of study visit
  • Experimental: Phase 1: Dose Escalation PEEL-224 Dose Level -1B
    Transition to a lower dose level will be determined by types of dose-limiting toxicities observed per the protocol, otherwise establishment of the MTD/RP2D will be according to the CRM model. * Baseline visit with assessments and imaging * Cycle 1 (21 day cycle): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Day 10: Myeloid growth factor (Pegfilgrastim or Filgrastim) administration 1x daily * Cycle 2 through End of Treatment (21 day cycles): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Imaging every 2 cycles until Cycle 6 and then every 3 cycles * End of study visit
  • Experimental: Phase 1: Dose Escalation PEEL-224 Dose Level -2
    Establishment of the MTD/RP2D will be according to the CRM design. * Baseline visit with assessments and imaging * Cycle 1 (21 day cycle): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Day 10: Myeloid growth factor (Pegfilgrastim or Filgrastim) administration 1x daily * Cycle 2 through End of Treatment (21 day cycles): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Imaging every 2 cycles until Cycle 6 and then every 3 cycles * End of study visit
  • Experimental: Phase 1: Dose Escalation PEEL-224 Dose Level 1
    Escalation to Dose Level 2 or establishment of the MTD/RP2D will be determined by the CRM design. * Baseline visit with assessments and imaging * Cycle 1 (21 day cycle): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Day 10: Myeloid growth factor (Pegfilgrastim or Filgrastim) administration 1x daily * Cycle 2 through End of Treatment (21 day cycles): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Imaging every 2 cycles until Cycle 6 and then every 3 cycles * End of study visit
  • Experimental: Phase 1: Dose Escalation PEEL-224 Dose Level 2
    Establishment of the MTD/RP2D will be determined by the CRM design. * Baseline visit with assessments and imaging * Cycle 1 (21 day cycle): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Day 10: Myeloid growth factor (Pegfilgrastim or Filgrastim) administration 1x daily * Cycle 2 through End of Treatment (21 day cycles): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Imaging every 2 cycles until Cycle 6 and then every 3 cycles * End of study visit
  • Experimental: Phase 2: Dose Expansion Ewing Sarcoma
    Administration of PEEL-224 will be at the RP2D, and safety monitoring rules will be applied for the occurrence of dose-limiting toxicities. 15 participants will be enrolled and will complete: * Baseline visit with assessments and imaging * Cycle 1 (21 day cycle): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Day 10: Myeloid growth factor (Pegfilgrastim or Filgrastim) administration 1x daily * Cycle 2 through End of Treatment (21 day cycles): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Imaging every 2 cycles until Cycle 6 and then every 3 cycles * End of study visit
  • Experimental: Phase 2: Dose Expansion DSRCT
    Administration of PEEL-224 will be at the RP2D, and safety monitoring rules will be applied for the occurrence of dose-limiting toxicities. 15 participants will be enrolled and will complete: * Baseline visit with assessments and imaging * Cycle 1 (21 day cycle): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Day 10: Myeloid growth factor (Pegfilgrastim or Filgrastim) administration 1x daily * Cycle 2 through End of Treatment (21 day cycles): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Imaging every 2 cycles until Cycle 6 and then every 3 cycles * End of study visit
  • Experimental: Phase 2: Dose Expansion Other Sarcoma
    Administration of PEEL-224 will be at the RP2D, and safety monitoring rules will be applied for the occurrence of dose-limiting toxicities. 15 participants will be enrolled and will complete: * Baseline visit with assessments and imaging * Cycle 1 (21 day cycle): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Day 10: Myeloid growth factor (Pegfilgrastim or Filgrastim) administration 1x daily * Cycle 2 through End of Treatment (21 day cycles): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Imaging every 2 cycles until Cycle 6 and then every 3 cycles * End of study visit

Primary Outcome Measure

Maximum Tolerated Dose (MTD) (Phase 1) [ Time Frame: Up to 35 days ]

Central Contacts

Locations (3)

FacilityCityStateZIPSite coordinators
Boston Children's HospitalBostonMassachusetts02115
David Shulman, MD
[email protected]
617-632-6670
David Shulman, MD (PRINCIPAL_INVESTIGATOR)
Brigham and Women's HospitalBostonMassachusetts02215
David Shulman, MD
[email protected]
617-632-6670
David Shulman, MD (PRINCIPAL_INVESTIGATOR)
Dana-Farber Cancer InstituteBostonMassachusetts02115
David Shulman, MD
[email protected]
617-632-6670
David Shulman, MD (PRINCIPAL_INVESTIGATOR)

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Boston Children's Hospital· Boston, MABrigham and Women's Hospital· Boston, MADana-Farber Cancer Institute· Boston, MA

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