RECRUITING

PEEL-224, Vincristine and Temozolomide in Pediatric Solid Tumors

Conditions

Refractory Solid Tumors Relapsed Solid Tumors Relapsed Neuroblastoma Refractory Neuroblastoma Relapsed Rhabdomyosarcoma Refractory Rhabdomyosarcoma Relapsed Refractory Solid Tumor

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2025-03

Study Completion:2031-04

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06721689

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:1 Year to 30 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion 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. Adequate available archival tumor tissue as described in Section 5.4.3. Tumor tissue from the most recent biopsy or resection is preferred, if adequate sample is available. If no archival tumor tissue is available, enrollment may be permitted with prior approval by the overall study PI or designee. 5. 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). 6. Females of childbearing potential must have a negative urine/serum pregnancy test. 7. Adequate bone marrow function * 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 * 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. 8. 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: 9. 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). 10. 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) 11. Prior treatment with irinotecan and/or temozolomide is permitted. 12. 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. 13. Subjects must agree to use sun protective measures while receiving treatment and for 4 weeks after the last dose of PEEL-224 14. Parental/guardian permission (informed consent) and if appropriate, child assent.	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.

Inclusion Criteria

Exclusion 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. Adequate available archival tumor tissue as described in Section 5.4.3. Tumor tissue from the most recent biopsy or resection is preferred, if adequate sample is available. If no archival tumor tissue is available, enrollment may be permitted with prior approval by the overall study PI or designee.
5. 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).
6. Females of childbearing potential must have a negative urine/serum pregnancy test.
7. Adequate bone marrow function
* 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
* 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.
8. 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:
9. 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).
10. 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)
11. Prior treatment with irinotecan and/or temozolomide is permitted.
12. 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.
13. Subjects must agree to use sun protective measures while receiving treatment and for 4 weeks after the last dose of PEEL-224
14. Parental/guardian permission (informed consent) and if appropriate, child assent.

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.

Contacts and Locations

Study Contact

Meghan Donnelly, MPH

CONTACT

267-426-9343

donnellymt@chop.edu

James Robinson, MSW, MPH

CONTACT

215-590-2053

robinsonj9@chop.edu

Principal Investigator

Jacquelyn Crane, MD

PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Study Locations (Sites)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104

United States

Collaborators and Investigators

Sponsor: Theodore Laetsch

Jacquelyn Crane, MD, PRINCIPAL_INVESTIGATOR, Children's Hospital of Philadelphia

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-03

Study Completion Date2031-04

Study Record Updates

Study Start Date2025-03

Study Completion Date2031-04

Terms related to this study

Keywords Provided by Researchers

Relapsed
Refractory
Solid Tumor

Additional Relevant MeSH Terms

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