PEEL-224, Vincristine and Temozolomide in Pediatric Solid Tumors

NCT06721689 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 24-022741
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 7

Brief Summary

The phase 1 primary objective is to determine the pediatric recommended phase 2 dose (RP2D) of PEEL-224 as a single agent (phase 1A) and in combination with vincristine and temozolomide (phase 1B). The phase 2 primary objective is to estimate the objective response rate (ORR) in children with refractory, progressive and relapsed NBL and rhabdomyosarcoma (RMS) treated with the RP2D of PEEL-224 in combination with vincristine and temozolomide.

Conditions

Refractory Solid Tumors; Relapsed Solid Tumors; Relapsed Neuroblastoma; Refractory Neuroblastoma; Relapsed Rhabdomyosarcoma; Refractory Rhabdomyosarcoma

Keywords

Relapsed; Refractory; Solid Tumor

Outcome Measures

Primary Outcomes (3)

• Phase 1A and Phase 1B: Number of participants who experience a dose limiting toxicity (DLT)

  The observation of a dose-limiting toxicity (DLT) or lack of observation of DLT in the period between treatment initiation up to initiation of cycle 2 treatment. A dose limiting toxicity (DLT) describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment.

  1 month

• Phase 2 Neuroblastoma Cohort (NBL): Number of paricptants who achieve a complete response (CR), partial response (PR), or minor response (MR)

  Objective response as assessed by the Revised International Neuroblastoma Response Criteria (INRC). Response is defined as complete response (CR), partial response (PR) or minor response (MR), using best response measured at any point prior to local control.

  2 years

• Phase 2 Rhabdomyosarcoma (RMS) Cohort: Number of participants who achieve a complete response (CR) or partial response (PR)

  Objective response as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Response is defined as complete response (CR) or partial response (PR), using best response measured at any point prior to local control.

  2 years

Secondary Outcomes (4)

• Number of subjects with an Adverse Event (AE) of greater than or equal to grade 3 at least possibly attributable to study treatment

  30 days after last dose

• Area under the plasma-concentration-time-curve of PEEL-224

  1 month

• Number of participants demonstrating anti-tumor activity of PEEL-224

  2 years

• Number of participants demonstrating anti-tumor activity of the combination of PEEL-224, vincristine and temozolomide

  2 years

Study Arms (2)

PEEL-224

EXPERIMENTAL

Phase 1A will test the safety, tolerability and PK profile of PEEL-224 as a single agent in pediatric patients with refractory, progressive and relapsed solid tumors.

Drug: PEEL-224

PEEL-224, Vincristine, and Temozolomide

EXPERIMENTAL

Phase 1B will test the safety, tolerability and pharmacokinetic profile of PEEL-224 in combination with vincristine and temozolomide in pediatric subjects with refractory, progressive and relapsed solid tumors. Phase 2 will preliminary evaluate the activity profile of PEEL-224 in combination with vincristine and temozolomide in pediatric patients with refractory, progressive and relapsed NBL and RMS.

Drug: PEEL-224; Drug: Vincristine; Drug: Temozolomide (TMZ)

Interventions

PEEL-224 DRUG

PEEL-224 (PEG-\[SN22\]4) is a novel topoisomerase I inhibitor

PEEL-224; PEEL-224, Vincristine, and Temozolomide

Vincristine DRUG

Vincristine is an inhibitor of microtubular formation which is approved by the Food and Drug Administration (FDA) and is commercially available.

PEEL-224, Vincristine, and Temozolomide

Temozolomide (TMZ) DRUG

Temozolomide is an alkylating agent which is approved by the FDA and is commercially available.

PEEL-224, Vincristine, and Temozolomide

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age:
• Phase 1: Age greater than or equal to 1 year and less than or equal to18 years
• Phase 2 Neuroblastoma (NBL) cohort: Age greater than or equal to 1 year and less than or equal to 30 years
• Phase 2 Rhabdomyosarcoma (RMS) cohort: Age greater than or equal to 1 year and less than or equal to18 years
• Diagnosis of:
• Phase 1: Refractory, progressive or relapsed non-central nervous system (CNS) solid tumors who have received at least 1 line of upfront therapy. Patients must have had histologic verification of their malignancy at original diagnosis or relapse
• Phase 2: Refractory, progressive or relapsed neuroblastoma (NBL) or rhabdomyosarcoma (RMS) who have received at least 1 line of upfront therapy. Patients must have had histologic verification of their malignancy at original diagnosis or relapse.
• Disease status:
• Phase 1: evaluable or measurable disease
• Phase 2, subjects with Neuroblastoma (NBL): evaluable or measurable disease by International Neuroblastoma Response Criteria (INRC); subjects with only bone marrow disease are not eligible
• Phase 2, subjects with rhabdomyosarcoma (RMS): measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST)1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 (age greater than 16 years) or Lansky Performance Status of at least 60 (age less than 16 years).
• Females of childbearing potential must have a negative urine/serum pregnancy test.
• Adequate bone marrow function
• Hematologic requirements for all subjects on phase 1 and subjects on phase 2 without malignant infiltration of the bone marrow:

You may not qualify if:

• Prior treatment with PEEL-224.
• Subjects receiving any other anti-cancer agents.
• Subjects with primary central nervous system (CNS) solid tumors or central nervous system (CNS) metastatic disease.
• Subjects with prior allogeneic stem cell or solid organ transplantation.
• Pregnant or lactating females.
• Subjects with a known history of human immunodeficiency virus (HIV), hepatitis B, and/or hepatitis C (testing not required as part of screening).
• Subjects with symptomatic congestive heart failure.

Sponsors & Collaborators

• Theodore Laetsch: lead
• Peel Therapeutics Inc: collaborator
• University of Pennsylvania: collaborator

Study Sites (7)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

NOT YET RECRUITING

University of California, San Francisco

San Francisco, California, 94143, United States

NOT YET RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

NOT YET RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

NOT YET RECRUITING

University of Utah Hospital

Salt Lake City, Utah, 84132, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Neuroblastoma; Rhabdomyosarcoma; Recurrence

Interventions

Vincristine; Temozolomide

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Jacquelyn Crane, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meghan Donnelly, MPH

CONTACT

267-426-9343; donnellymt@chop.edu

James Robinson, MSW, MPH

CONTACT

215-590-2053; robinsonj9@chop.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Developmental Therapeutics Program and Very Rare Malignant Tumors Program

Study Record Dates

• First Submitted: December 2, 2024
• First Posted: December 6, 2024
• Study Start: March 23, 2025
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2031
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)