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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:
Full description
This is an open-label, single-arm, non-randomized, phase I/II trial 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. This is the first time that PEEL-224 will be given in combination with Vincristine and Temozolomide to humans.
In Phase 1, the safety and tolerability of PEEL-224 in combination with Vincristine and Temozolomide will be assessed by dose escalation and establishment of a Recommended Phase 2 Dose. In Phase 2 the efficacy of the drug combination will be assessed in three separate cohorts of participants.
The U.S. Food and Drug Administration (FDA) has not approved PEEL-224 as a treatment for Relapsed or Refractory Sarcoma.
The U.S. Food and Drug Administration (FDA) has not approved Vincristine and Temozolomide for Relapsed or Refractory Sarcoma, but it has been approved for other uses.
The research study procedures include screening for eligibility, study treatment in-clinic visits, X-rays, Computerized Tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, or Positron Emission Tomography (PET) scans, blood tests, urine tests, and electrocardiograms (ECGs).
Participants will receive study treatment for up to 34 cycles (approximately 2 years) and will be followed for up to 1 year after the last participant has received the last dose of treatment.
It is expected that about 63 people will take part in this research study.
PEEL Therapeutics is funding this research study by providing the study drug, PEEL-224.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
-Patients in all cohorts must have relapsed or refractory disease after standard therapy.
Inclusion Criteria Phase 1 (only) diagnosis requirements:
-Patients must have:
Inclusion Criteria Phase 2 (only) diagnosis requirements
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:
DSRCT cohort: Patients must have:
Other sarcoma cohort: Patients must have:
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:
Disease:
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.
Exclusion criteria
Primary purpose
Allocation
Interventional model
Masking
63 participants in 9 patient groups
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Central trial contact
David Shulman, MD
Data sourced from clinicaltrials.gov
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