PEEL-224, Vincristine and Temozolomide in Pediatric Solid Tumors (PEEL-224)

A Phase 1/2 Clinical Trial of the Novel Topoisomerase I Inhibitor PEEL-224 as a Single Agent and in Combination With Vincristine and Temozolomide in Children With Refractory, Progressive or Relapsed Solid Tumors

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.

Study Overview

• Status: Recruiting
• Conditions: Refractory Neuroblastoma; Refractory Rhabdomyosarcoma; Refractory Solid Tumors; Relapsed Solid Tumors; Relapsed Neuroblastoma; Relapsed Rhabdomyosarcoma
• Intervention / Treatment: Drug: PEEL-224; Drug: Vincristine; Drug: Temozolomide (TMZ)

Detailed Description

PEEL-224 will be a multi-institutional study conducted at pediatric cancer centers. Phase 1 will enroll approximately 24 subjects (maximum of 12 evaluable subjects in phase 1A and 12 evaluable subjects in phase 1B) between ages 1 to 18 years of age with a refractory, progressive or relapsed solid tumor. Phase 2 will enroll a maximum of 18 evaluable subjects with refractory, progressive or relapsed NBL and a maximum of 17 evaluable subjects with refractory, progressive or relapsed RMS. PEEL-224 will be administered at the assigned dose on days 1 and 8 of 21-day cycles as a single agent (phase 1A) or in combination with vincristine on days 1 and 8 and temozolomide on days 1-5 (phase 1B and phase 2). Subjects may continue protocol therapy for up to 24 cycles (approximately 18 months) in the absence of progressive disease or unacceptable toxicity. Subjects will be monitored with physical exams and labs on days 1 and 8 of each cycle and disease response assessments and patient reported outcome assessments will be performed after cycles 2, 4, 6, 9, 12, 18, and 24. During phase 1, PK blood samples will be drawn during cycle 1. The primary phase 1 endpoints are cycle 1 dose limiting toxicity (DLT) to define the RP2D. The primary phase 2 endpoint is best overall objective response to define the ORR.

• Study Type: Interventional
• Enrollment (Estimated): 59
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Meghan Donnelly, MPH; Phone Number: 267-426-9343; Email: donnellymt@chop.edu
• Study Contact Backup: Name: James Robinson, MSW, MPH; Phone Number: 215-590-2053; Email: robinsonj9@chop.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Not yet recruiting
      • Cedars-Sinai Medical Center
      • Principal Investigator: Leo Mascarhenhas, MD
    • San Francisco, California, United States, 94143
      • Not yet recruiting
      • University of California, San Francisco
      • Principal Investigator: Jennifer Michlitsch, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Not yet recruiting
      • Dana-Farber Cancer Institute
      • Principal Investigator: David Shulman, MD
    • Boston, Massachusetts, United States, 02115
      • Not yet recruiting
      • Boston Children's Hospital
      • Principal Investigator: David Shulman, MD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Contact: Meghan Donnelly, MPH; Phone Number: 267-426-9343; Email: donnellymt@chop.edu
      • Principal Investigator: Jacquelyn Crane, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Not yet recruiting
      • Texas Children's Hospital
      • Principal Investigator: Jennifer Foster, MD
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Not yet recruiting
      • University of Utah Hospital
      • Principal Investigator: Matthew Dietz, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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

2. 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.

3. 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.
4. 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).
5. Females of childbearing potential must have a negative urine/serum pregnancy test.

6. Adequate bone marrow function

   Hematologic requirements for all subjects on phase 1 and subjects on phase 2 without malignant infiltration of the bone marrow:

   • Absolute neutrophil count (ANC) greater than or equal to 750/mm3 (greater than or equal to 7 days since last dose of short acting myeloid growth factor medications (e.g. filgrastim) and greater than or equal to 14 days since last dose of long-acting myeloid medications (e.g. peg-filgrastim)
   • Platelet count ≥ 75,000 mm3 (greater than or equal to 14 days since last dose of thrombopoietin receptor agonist such as romiplostim and without platelet transfusion within previous 7 days)
   • Not refractory to packed red blood cell transfusions

   Hematologic requirements for subjects on phase 2 with malignant infiltration of the bone marrow:

   • Absolute neutrophil count (ANC) greater than or equal to 500/mm3 (greater than or equal to 7 days since last dose of short acting myeloid growth factor medications (e.g. filgrastim) and greater than or equal to 14 days since last dose of long-acting myeloid medications (e.g. peg-filgrastim))
   • Platelet count greater than or equal to 50,000/mm3 (greater than or equal to 14 days since last dose of thrombopoietin receptor agonist such as romiplostim and without platelet transfusion within previous 7 days)
   • Not refractory to packed red blood cell transfusions
   • Patients on phase 2 with malignant infiltration of the bone marrow will not be evaluable for hematologic toxicity.

7. Adequate renal function as evidenced by creatinine clearance as calculated by the Schwartz equation (see below), radioisotope glomerular filtration rate (GFR) greater than or equal to 70 mL/min/1.73 m2, or maximum serum creatinine as below:

   Age Maximum Serum Creatinine (mg/dL)

   Male Female 1 to less than 2 years 0.6 0.6 2 to less than 6 years 0.8 0.8 6 to less than 10 years 1 1 10 to less than 13 years 1.2 1.2 13 to less than 16 years 1.5 1.4 greater than 16 years 1.7 1.4 Threshold derived from the Schwartz formula for estimating glomerular filtration rate (GFR) (Schwartz et al., J.Peds, 106:522,1985) utilizing child length and stature data published by the CDC The Schwartz equation for subjects less than 18 years of age: eGFR (mL/min/1.73 m2) = 0.413 x [height (cm)/serum creatinine (mg/dL)]

8. Adequate liver function

   • Aspartate Aminotransferase (AST/SGOT): less than or equal to 3 times the upper limit of normal (ULN) or less than or equal to 5 the upper limit of normal if attributable to disease involvement. For the purpose of this study, the upper limit of normal (ULN) for Aspartate Aminotransferase (AST) is 50 U/L.
   • Alanine Aminotransferase (ALT/SGPT): less than or equal to 3 times the ULN or less than or equal to 5 the upper limit of normal if attributable to disease involvement. For the purpose of this study, the upper limit of normal (ULN) for Alanine Aminotransferase (ALT) is 45 U/L.
   • Total bilirubin: less than or equal to 1.5 times the upper limit of normal with the exception of patients with Gilbert's syndrome who must have bilirubin less than 3X institutional upper limit of normal (ULN).

9. Prior Therapy: Patients must have had resolution of acute toxic effects of prior therapy to grade less than or equal to 1 according to the National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v 5.0 except organ function as noted above, adverse events (AE) that are considered clinically non-significant (i.e. alopecia), or controlled on supportive care (i.e. nausea/vomiting, hypothyroidism). Patients must meet the following minimum washout periods prior to enrollment:

   • Myelosuppressive chemotherapy: At least 14 days after the last dose of myelosuppressive chemotherapy
   • Small molecule targeted therapy: At least 7 days following the last dose of a small molecule targeted agent.
   • Antibody therapy: At least 21 days following the last dose of antibody including anti-GD2 monoclonal antibody.
   • Cellular therapy: At least 42 days following completion of a cellular therapy agent (e.g. modified T cells, NK cells, dendritic cells)
   • Autologous hematopoietic stem cell transplant and stem cell boost: Subjects must be at least 60 days from day 0 of an autologous stem cell transplant or stem cell boost.
   • Myeloid growth factors: At least 7 days following short-acting myeloid growth factor (e.g. filgrastim) and at least 14 days following the last dose of long-acting myeloid growth factor (e.g. peg-filgrastim)
   • Thrombopoietin receptor agonists: At least 14 days following last dose of thrombopoietin receptor agonist such as romiplostim
   • Interleukins, interferons, and cytokines (other than hematopoietic growth factors): At least 21 days following the completion of interleukins, interferon, or cytokines, including IL-2

   • Radiotherapy:

     • At least 14 days after limited field radiation therapy;
     • At least 90 days after total body irradiation, craniospinal radiotherapy; or radiation to greater than 50% of pelvis;
     • At least 42 days must have elapsed if other substantial BM radiation.
   • Radiopharmaceutical therapy (e.g. radiolabeled antibody, 131I- MIBG): At least 42 days after radiopharmaceutical therapy
   • Major Surgery: At least 2 weeks from prior major surgical procedure. Note: Biopsy, CNS shunt placement/revision, and central line placement/removal are not considered major.
   • Strong CYP1A2 and/or CYP3A4 inhibitors and/or inducers: At least 14 days following use of a strong CYP1A2 and/or CYP3A4 inhibitor and/or inducer. See Appendix 1 for examples. (Note that levofloxacin is permitted when clinically indicated)
10. Prior treatment with irinotecan and/or temozolomide is permitted.
11. Female patients of reproductive potential must agree to use a highly effective contraceptive method for the duration of study therapy and for at least six months after the final dose of PEEL-224. Males of reproductive potential with a female partner of child-bearing potential must use a highly effective for the duration of the study and for at least six months after the final dose of PEEL-224.
12. Subjects must agree to use sun protective measures while receiving treatment and for 4 weeks after the last dose of PEEL-224
13. Parental/guardian permission (informed consent) and if appropriate, child assent.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PEEL-224; 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 (PEG-[SN22]4) is a novel topoisomerase I inhibitor
Experimental: PEEL-224, Vincristine, and Temozolomide; 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; PEEL-224 (PEG-[SN22]4) is a novel topoisomerase I inhibitor; Drug: Vincristine; Vincristine is an inhibitor of microtubular formation which is approved by the Food and Drug Administration (FDA) and is commercially available.; Drug: Temozolomide (TMZ); Temozolomide is an alkylating agent which is approved by the FDA and is commercially available.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with an Adverse Event (AE) of greater than or equal to grade 3 at least possibly attributable to study treatment	Adverse Events (AEs) will be graded by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	30 days after last dose
Area under the plasma-concentration-time-curve of PEEL-224	To characterize the pharmacokinetic (PK) profile of free SN22 and SN22 bound to PEG (PEEL-224)	1 month
Number of participants demonstrating anti-tumor activity of PEEL-224	To preliminarily evaluate antitumor activity of PEEL-224 by estimating event-free survival (EFS)	2 years
Number of participants demonstrating anti-tumor activity of the combination of PEEL-224, vincristine and temozolomide	To preliminarily evaluate antitumor activity of the combination of PEEL-224, vincristine and temozolomide by estimating event-free survival (EFS )	2 years

Collaborators and Investigators

• Sponsor: Theodore Laetsch
• Collaborators: University of Pennsylvania; Peel Therapeutics Inc
• Investigators: Principal Investigator: Jacquelyn Crane, MD, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2025
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2031

Study Registration Dates

• First Submitted: December 2, 2024
• First Submitted That Met QC Criteria: December 5, 2024
• First Posted (Actual): December 6, 2024

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Relapsed; Refractory; Solid Tumor
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Sarcoma; Neoplasms, Connective and Soft Tissue; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Muscle Tissue; Myosarcoma; Pathological Conditions, Signs and Symptoms; Recurrence; Neuroblastoma; Rhabdomyosarcoma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Alkaloids; Dacarbazine; Triazenes; Imidazoles; Indoles; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indolizidines; Indolizines; Temozolomide; Vincristine
• Other Study ID Numbers: 24-022741

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No