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)
Evaluable or measurable disease; and
Histologic diagnosis of sarcoma
RECIST measurable disease at study entry;
Histologic diagnosis consistent with Ewing sarcoma; and
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.
Sequential
PEEL-224
DrugTopoisomerase 1 inhibitor, 200mg amber vial, via intravenous (into the vein) infusion per protocol.
Temozolomide
DrugAlkylating agent, 5, 20, 100, 140, 180, or 250 mg capsule, taken orally per standard of care.
Vincristine
DrugVinca alkaloid, 1 or 2mL vials, via intravenous (into the vein) infusion per institutional policy.
Pegfilgrastim
Biological/VaccineMyeloid growth factor administered per institutional standards.
Filgrastim
Biological/VaccineMyeloid growth factor administered per institutional standards.
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Treatment groupsSee each treatment group below.
Maximum Tolerated Dose (MTD) (Phase 1)
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)
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)
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)
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 Other Sarcoma Cohort
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).
Median Progression-Free Survival (PFS) Other Sarcoma Cohort
Progression-Free Survival (PFS) based on the Kaplan-Meier method is defined as the time from registration to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation.
Overall Survival (OS) Other Sarcoma Cohort
Overall Survival (OS) based on the Kaplan-Meier method is defined as the time from registration to death due to any cause, or censored at date last known alive.
Median PFS EWS Cohort
PFS based on the Kaplan-Meier method is defined as the time from registration to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation.
Click on the lead sponsor to view all of their trials.
David S Shulman, MD
Lead sponsor
Dana-Farber Cancer Institute
Sponsor institution
Peel Therapeutics Inc
Collaborator
