RECRUITING

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

Conditions

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

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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

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)

Official Title

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

Quick Facts

Study Start:2025-01-27

Study Completion:2029-09-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06709495

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:12 Years to 49 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* Evaluable or measurable disease; and * Histologic diagnosis of sarcoma * 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 * Absolute neutrophil count (ANC) ≥ 1,000/uL * Platelet count ≥100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) * ANC ≥750 /uL * Platelets ≥50,000 /uL (may receive platelet transfusions) Not known to be refractory to red cell and/or platelet transfusions. * Age: 12 to \< 13 years, Maximum Serum Creatinine (mg/dL): Male 1.2, Female 1.2 * Age 13 to \< 16 years, Maximum Serum Creatinine (mg/dL): Male 1.5, Female 1.4 * Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age * SGPT (ALT) ≤110 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L. * Adequate Cardiac Function: QTc \< 480 msec * Myelosuppressive chemotherapy: At least 14 days after the last dose of myelosuppressive chemotherapy * Radiotherapy: * At least 14 days after local XRT (small port, including cranial radiation); * At least 90 days must have elapsed after prior TBI, craniospinal XRT or if \>50% radiation of pelvis; * At least 42 days must have elapsed if other substantial BM radiation. * Small molecule biologic therapy: At least 7 days following the last dose of a biologic agent. * Monoclonal antibody: At least 21 days must have elapsed after the last dose of antibody. * Myeloid and platelet growth factors: At least 14 days following the last dose of long-acting myeloid growth factor (e.g. Neulasta) or 7 days following short-acting myeloid or platelet growth factor. * Autologous hematopoietic stem cell transplant and stem cell boost: Patients must be at least 60 days from day 0 of an autologous stem cell transplant or stem cell boost. * Cellular Therapies (e.g., CART, NK-cell based therapy): The patient must be and at least 42 days from cellular therapy administration. * 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. * Irinotecan, liposomal irinotecan, and/or temozolomide: Patients may have received prior irinotecan, liposomal irinotecan, and/or temozolomide. NOTE: 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. * Patients with CNS metastatic disease will not be eligible for the phase 2 EWS and DSRCT cohorts. * Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. * The effects of PEEL-224 in combination with temozolomide and vincristine on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of PEEL-224 administration. * Ability to understand and/or the willingness of the patient (or parent or legally authorized representative, if minor) to provide informed consent, using an institutionally approved informed consent procedure. * Any participant must obtain prior approval from insurance to reimburse oral temozolomide for the duration of the study or agree to self-pay for oral temozolomide.	* 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.

Inclusion Criteria

Exclusion Criteria

* Evaluable or measurable disease; and
* Histologic diagnosis of sarcoma
* 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
* Absolute neutrophil count (ANC) ≥ 1,000/uL
* Platelet count ≥100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
* ANC ≥750 /uL
* Platelets ≥50,000 /uL (may receive platelet transfusions) Not known to be refractory to red cell and/or platelet transfusions.
* Age: 12 to \< 13 years, Maximum Serum Creatinine (mg/dL): Male 1.2, Female 1.2
* Age 13 to \< 16 years, Maximum Serum Creatinine (mg/dL): Male 1.5, Female 1.4
* Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
* SGPT (ALT) ≤110 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.
* Adequate Cardiac Function: QTc \< 480 msec
* Myelosuppressive chemotherapy: At least 14 days after the last dose of myelosuppressive chemotherapy
* Radiotherapy:
* At least 14 days after local XRT (small port, including cranial radiation);
* At least 90 days must have elapsed after prior TBI, craniospinal XRT or if \>50% radiation of pelvis;
* At least 42 days must have elapsed if other substantial BM radiation.
* Small molecule biologic therapy: At least 7 days following the last dose of a biologic agent.
* Monoclonal antibody: At least 21 days must have elapsed after the last dose of antibody.
* Myeloid and platelet growth factors: At least 14 days following the last dose of long-acting myeloid growth factor (e.g. Neulasta) or 7 days following short-acting myeloid or platelet growth factor.
* Autologous hematopoietic stem cell transplant and stem cell boost: Patients must be at least 60 days from day 0 of an autologous stem cell transplant or stem cell boost.
* Cellular Therapies (e.g., CART, NK-cell based therapy): The patient must be and at least 42 days from cellular therapy administration.
* 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.
* Irinotecan, liposomal irinotecan, and/or temozolomide: Patients may have received prior irinotecan, liposomal irinotecan, and/or temozolomide. NOTE: 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.
* Patients with CNS metastatic disease will not be eligible for the phase 2 EWS and DSRCT cohorts.
* Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* The effects of PEEL-224 in combination with temozolomide and vincristine on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of PEEL-224 administration.
* Ability to understand and/or the willingness of the patient (or parent or legally authorized representative, if minor) to provide informed consent, using an institutionally approved informed consent procedure.
* Any participant must obtain prior approval from insurance to reimburse oral temozolomide for the duration of the study or agree to self-pay for oral temozolomide.

* 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.

Contacts and Locations

Study Contact

David Shulman, MD

CONTACT

617-632-6670

david_shulman@dfci.harvard.edu

Principal Investigator

David Shulman, MD

PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Study Locations (Sites)

Boston Children's Hospital

Boston, Massachusetts, 02115

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115

United States

Brigham and Women's Hospital

Boston, Massachusetts, 02215

United States

Collaborators and Investigators

Sponsor: David S Shulman, MD

David Shulman, MD, PRINCIPAL_INVESTIGATOR, Dana-Farber Cancer Institute

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 Date2025-01-27

Study Completion Date2029-09-01

Study Record Updates

Study Start Date2025-01-27

Study Completion Date2029-09-01

Terms related to this study

Keywords Provided by Researchers

Sarcoma
Sarcoma, Ewing
Desmoplastic Small Round Cell Tumor
Refractory Sarcoma
Relapsed Sarcoma
osteosarcoma
rhabdomyosarcoma

Additional Relevant MeSH Terms

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