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Topoisomerase I inhibitors

PEEL-224 + Vincristine + Temozolomide for Sarcoma

Phase 1 & 2

Waitlist Available

Led By David Shulman, MD

Research Sponsored by David S Shulman, MD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age: ≥ 12 years and ≤ 49 years

Organ and marrow function requirements including hematologic, renal, liver, and cardiac function

Must not have

Patients who had progressive disease while receiving irinotecan and temozolomide in combination in Phase 2 EWS and DSRCT cohorts

Patients who have received a solid organ or allogeneic stem cell transplant

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years (based on accrual duration of 2 years)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called PEEL-224 along with two other drugs, Vincristine and Temozolomide, to see how effective they are in treating Ewing

Who is the study for?

This trial is for adolescents and young adults with certain types of sarcomas that have come back or didn't respond to previous treatments. Participants should be diagnosed with conditions like Ewing Sarcoma or Desmoplastic Small Round Cell Tumor, among others.

What is being tested?

The study tests a new drug, PEEL-224, combined with Vincristine and Temozolomide. It aims to find out how effective this mix is against various sarcomas in those who've had relapses or refractory disease.

What are the potential side effects?

Possible side effects include reactions related to the immune system due to PEEL-224, nerve damage from Vincristine, blood cell count changes from Temozolomide, and bone pain or discomfort from Pegfilgrastim/Filgrastim.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 12 and 49 years old.

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My blood, kidney, liver, and heart are functioning well.

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I am mostly able to care for myself, regardless of my age.

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My condition did not improve after standard treatment.

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My insurance covers or I can self-pay for oral temozolomide.

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I weigh at least 40 kg.

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I have had cancer before or have another type of cancer now.

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I have sarcoma with measurable disease.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My cancer progressed despite treatment with irinotecan and temozolomide.

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I have had a solid organ or bone marrow transplant.

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I have previously been treated with PEEL-224.

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I do not have any uncontrolled illnesses.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years (based on accrual duration of 2 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years (based on accrual duration of 2 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years (based on accrual duration of 2 years) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum Tolerated Dose (MTD) (Phase 1)

Number of Participants with DLTs (Phase 2)

Number of Participants with Dose-Limiting Toxicities (Phase 1)

+2 more

Secondary study objectives

Area Under the Plasma Concentration Versus Time Curve (AUC) of PEEL-224

Circulating Tumor DNA (ctDNA) Burden EWS Cohort at Baseline

Median Duration of Complete Response (CR) (Phase 2)

+16 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

9Treatment groups

Experimental Treatment

Group I: Phase 2: Dose Expansion Other SarcomaExperimental Treatment5 Interventions

Administration of PEEL-224 will be at the RP2D, and safety monitoring rules will be applied for the occurrence of dose-limiting toxicities. 15 participants will be enrolled and will complete: * Baseline visit with assessments and imaging * Cycle 1 (21 day cycle): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Day 10: Myeloid growth factor (Pegfilgrastim or Filgrastim) administration 1x daily * Cycle 2 through End of Treatment (21 day cycles): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Imaging every 2 cycles until Cycle 6 and then every 3 cycles * End of study visit

Group II: Phase 2: Dose Expansion Ewing SarcomaExperimental Treatment5 Interventions

Group III: Phase 2: Dose Expansion DSRCTExperimental Treatment5 Interventions

Group IV: Phase 1: Dose Escalation PEEL-224 Dose Level 2Experimental Treatment5 Interventions

Establishment of the MTD/RP2D will be determined by the CRM design. * Baseline visit with assessments and imaging * Cycle 1 (21 day cycle): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Day 10: Myeloid growth factor (Pegfilgrastim or Filgrastim) administration 1x daily * Cycle 2 through End of Treatment (21 day cycles): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Imaging every 2 cycles until Cycle 6 and then every 3 cycles * End of study visit

Group V: Phase 1: Dose Escalation PEEL-224 Dose Level 1Experimental Treatment5 Interventions

Escalation to Dose Level 2 or establishment of the MTD/RP2D will be determined by the CRM design. * Baseline visit with assessments and imaging * Cycle 1 (21 day cycle): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Day 10: Myeloid growth factor (Pegfilgrastim or Filgrastim) administration 1x daily * Cycle 2 through End of Treatment (21 day cycles): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Imaging every 2 cycles until Cycle 6 and then every 3 cycles * End of study visit

Group VI: Phase 1: Dose Escalation PEEL-224 Dose Level 0Experimental Treatment5 Interventions

Up to 15 participants will be enrolled using a Bayesian design, the Continual Reassessment Method (CRM), to determine the maximum tolerated dose of PEEL-224 and starting at Dose Level 0. Transition to a lower dose level will be determined by types of dose-limiting toxicities observed per the protocol. * Baseline visit with assessments and imaging * Cycle 1 (21 day cycle): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Day 10: Myeloid growth factor (Pegfilgrastim or Filgrastim) administration 1x daily * Cycle 2 through End of Treatment (21 day cycles): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Imaging every 2 cycles until Cycle 6 and then every 3 cycles * End of study visit

Group VII: Phase 1: Dose Escalation PEEL-224 Dose Level -2Experimental Treatment5 Interventions

Establishment of the MTD/RP2D will be according to the CRM design. * Baseline visit with assessments and imaging * Cycle 1 (21 day cycle): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Day 10: Myeloid growth factor (Pegfilgrastim or Filgrastim) administration 1x daily * Cycle 2 through End of Treatment (21 day cycles): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Imaging every 2 cycles until Cycle 6 and then every 3 cycles * End of study visit

Group VIII: Phase 1: Dose Escalation PEEL-224 Dose Level -1BExperimental Treatment5 Interventions

Transition to a lower dose level will be determined by types of dose-limiting toxicities observed per the protocol, otherwise establishment of the MTD/RP2D will be according to the CRM model. * Baseline visit with assessments and imaging * Cycle 1 (21 day cycle): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Day 10: Myeloid growth factor (Pegfilgrastim or Filgrastim) administration 1x daily * Cycle 2 through End of Treatment (21 day cycles): * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 and 8: Predetermined dose of PEEL-224 1x daily and predetermined dose of Vincristine 1x daily * Imaging every 2 cycles until Cycle 6 and then every 3 cycles * End of study visit

Group IX: Phase 1: Dose Escalation PEEL-224 Dose Level -1AExperimental Treatment5 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Vincristine

2003

Completed Phase 4

~2970

Filgrastim

2000

Completed Phase 3