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Phase 1/2 PEEL-224 for Relapsed or Refractory Sarcomas

This study is testing a new drug called PEEL-224, combined with two existing drugs, Vincristine and Temozolomide, for adolescents and young adults with sarcomas that have come back or not responded to previous treatments. This includes Ewing Sarcoma and Desmoplastic Small Round Cell Tumor, among other sarcomas. The study aims to find a safe dose of PEEL-224 (Phase 1) and then see how well this combination works (Phase 2). You may be able to join if you are between 12 and 49 years old and have a sarcoma that has relapsed or is refractory. The study is enrolling 63 participants.

Study design
This is a Phase 1/2, open-label, single-arm study, meaning all participants will receive the study treatment, and everyone involved will know which treatment is being given. It is not randomized. The study plans to enroll 63 participants.
What's involved
You would undergo screening to see if you qualify, receive study treatment during clinic visits, and have procedures like X-rays, CT scans, MRI scans, PET scans, blood tests, urine tests, and ECGs.
Compensation
Not stated in the trial record.
Follow-up
The primary endpoints for safety and tolerability are measured for up to 35 days after treatment.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT06709495

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

Recruiting
PHASE1Ages 12–49InterventionalTreatment
David S Shulman, MD
~63 participants
Updated 2026-02-19 on ClinicalTrials.gov
What's tested:PEEL-224TemozolomideVincristinePegfilgrastimFilgrastim

At a glance

Recruiting sites
1 of 3 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Maximum Tolerated Dose (MTD) (Phase 1)
Measured over Up to 35 days
+4 more outcomes measured

Conditions

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

Explore related trials

Desmoplastic Small Round Cell TumorEwing SarcomaOsteosarcomaRhabdomyosarcomaSarcomaEWSR1::WT1FET-ETS

Where it's being run

3 sites across 1 states
Massachusetts3

Study leadership

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

Who to contact

David Shulman, MD
[email protected]
617-632-6670
Email the study team

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Do you actually qualify for this trial?

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Eligibility criteria

Inclusion

Patients in all cohorts must have relapsed or refractory disease after standard therapy.
Patients must have:
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)
Hematologic Requirements for Subjects with Bone Marrow Involvement by Disease:
ANC ≥750 /uL
Platelets ≥50,000 /uL (may receive platelet transfusions) Not known to be refractory to red cell and/or platelet transfusions.
Adequate Renal Function: Creatinine clearance or radioisotope GFR ≥70ml/min/1.73 m2 or A serum creatinine based on age/sex as follows:
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
≥ 16 years, Maximum Serum Creatinine (mg/dL): Male 1.7, Female 1.4
Adequate Liver Function:
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
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy except organ function as noted above. Patients must meet the following minimum washout periods prior to enrollment:
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.
For patients with metastatic disease to the CNS enrolling to the phase 1 portion of the trial or the "other sarcoma" cohort, any baseline neurologic deficits (including seizure) must be stable for at least one week prior to study enrollment. Patients with CNS metastatic disease receiving corticosteroids must be on a stable or decreasing dose at time of study entry.
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.

Exclusion

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.

What this trial measures

  • Maximum Tolerated Dose (MTD) (Phase 1)Up to 35 days

    The MTD is determined by a Continual Reassessment Method (CRM) design and defined as the dose level with the posterior probability of dose-limiting toxicity (DLT) closest to the target toxicity rate of 0.3 with a maximum sample size of 15. The DLT observation period is up to 35 days long, beginning at the first dose of any of the three drugs in cycle 1 and ending at the occurrence of a DLT.

  • Number of Participants with Dose-Limiting Toxicities (Phase 1)Up to 35 days

    Any ≥ Grade 2 CTCAE v5 adverse events that are possibly, probably, or definitely attributable to the combination of Vincristine, PEEL-224, and Temozolomide and within the first 35 days, beginning at the first dose of any of the three drugs in cycle 1 and ending at the occurrence of DLT or at the start of treatment in cycle 2 (whichever occurs first). To be evaluable for dose-limiting toxicity, a participant must also receive at least 75% of prescribed agents in cycle 1 and be followed for at least 35 days during cycle 1 or to the start of cycle 2 (whichever occurs first).

  • Number of Participants with DLTs (Phase 2)Up to 35 days

    A safety monitoring rule will be applied to Phase 2 of the study for the overall participant cohort. The DLT observation period is up to 35 days long, beginning at the first dose of any of the three drugs in cycle 1 and ending at the occurrence of DLT or at the start of treatment in cycle 2 (whichever occurs first).

  • Objective Response Rate EWS Cohort (Phase 2)Up to 5 years (based on accrual duration of 2 years)

    ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. Evaluable participants must have measurable disease at screening, be treated at RP2D dose, have received at least one dose of study drug, and either have evidence of clinical progression or have had at least one follow-up disease evaluation of their RECIST measurable disease after initiation of protocol therapy. The proportion of responders is calculated as the (number of responders) / (number of evaluable participants).

  • Objective Response Rate DSRCT Cohort (Phase 2)Up to 5 years (based on accrual duration of 2 years)

    ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. Evaluable participants must have measurable disease at screening, be treated at RP2D dose, have received at least one dose of study drug, and either have evidence of clinical progression or have had at least one follow-up disease evaluation of their RECIST measurable disease after initiation of protocol therapy. The proportion of responders is calculated as the (number of responders) / (number of evaluable participants).