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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 63
- 试验地点
- 3
- 主要终点
- Maximum Tolerated Dose (MTD) (Phase 1)
研究概览
简要总结
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)
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 49 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients in all cohorts must have relapsed or refractory disease after standard therapy.
- •Inclusion Criteria Phase 1 (only) diagnosis requirements:
- •Patients must have:
- •Evaluable or measurable disease; and
- •Histologic diagnosis of sarcoma
- •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:
- •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.
- 另有 6 项未显示
排除标准
- •Patients who have received prior treatment with PEEL-
- •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-
- •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-
- •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.
研究组 & 干预措施
Phase 1: Dose Escalation PEEL-224 Dose Level 0
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
干预措施: PEEL-224 (Drug)
Phase 1: Dose Escalation PEEL-224 Dose Level 0
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
干预措施: Temozolomide (Drug)
Phase 1: Dose Escalation PEEL-224 Dose Level 0
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
干预措施: Vincristine (Drug)
Phase 1: Dose Escalation PEEL-224 Dose Level 0
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
干预措施: Pegfilgrastim (Biological)
Phase 1: Dose Escalation PEEL-224 Dose Level 0
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
干预措施: Filgrastim (Biological)
Phase 1: Dose Escalation PEEL-224 Dose Level -1A
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
干预措施: PEEL-224 (Drug)
Phase 1: Dose Escalation PEEL-224 Dose Level -1A
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
干预措施: Temozolomide (Drug)
Phase 1: Dose Escalation PEEL-224 Dose Level -1A
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
干预措施: Vincristine (Drug)
Phase 1: Dose Escalation PEEL-224 Dose Level -1A
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
干预措施: Pegfilgrastim (Biological)
Phase 1: Dose Escalation PEEL-224 Dose Level -1A
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
干预措施: Filgrastim (Biological)
Phase 1: Dose Escalation PEEL-224 Dose Level -1B
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
干预措施: PEEL-224 (Drug)
Phase 1: Dose Escalation PEEL-224 Dose Level -1B
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
干预措施: Temozolomide (Drug)
Phase 1: Dose Escalation PEEL-224 Dose Level -1B
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
干预措施: Vincristine (Drug)
Phase 1: Dose Escalation PEEL-224 Dose Level -1B
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
干预措施: Pegfilgrastim (Biological)
Phase 1: Dose Escalation PEEL-224 Dose Level -1B
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
干预措施: Filgrastim (Biological)
Phase 1: Dose Escalation PEEL-224 Dose Level -2
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
干预措施: PEEL-224 (Drug)
Phase 1: Dose Escalation PEEL-224 Dose Level -2
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
干预措施: Temozolomide (Drug)
Phase 1: Dose Escalation PEEL-224 Dose Level -2
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
干预措施: Vincristine (Drug)
Phase 1: Dose Escalation PEEL-224 Dose Level -2
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
干预措施: Pegfilgrastim (Biological)
Phase 1: Dose Escalation PEEL-224 Dose Level -2
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
干预措施: Filgrastim (Biological)
Phase 1: Dose Escalation PEEL-224 Dose Level 1
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
干预措施: PEEL-224 (Drug)
Phase 1: Dose Escalation PEEL-224 Dose Level 1
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
干预措施: Temozolomide (Drug)
Phase 1: Dose Escalation PEEL-224 Dose Level 1
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
干预措施: Vincristine (Drug)
Phase 1: Dose Escalation PEEL-224 Dose Level 1
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
干预措施: Pegfilgrastim (Biological)
Phase 1: Dose Escalation PEEL-224 Dose Level 1
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
干预措施: Filgrastim (Biological)
Phase 1: Dose Escalation PEEL-224 Dose Level 2
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
干预措施: PEEL-224 (Drug)
Phase 1: Dose Escalation PEEL-224 Dose Level 2
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
干预措施: Temozolomide (Drug)
Phase 1: Dose Escalation PEEL-224 Dose Level 2
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
干预措施: Vincristine (Drug)
Phase 1: Dose Escalation PEEL-224 Dose Level 2
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
干预措施: Pegfilgrastim (Biological)
Phase 1: Dose Escalation PEEL-224 Dose Level 2
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
干预措施: Filgrastim (Biological)
Phase 2: Dose Expansion Ewing Sarcoma
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
干预措施: PEEL-224 (Drug)
Phase 2: Dose Expansion Ewing Sarcoma
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
干预措施: Temozolomide (Drug)
Phase 2: Dose Expansion Ewing Sarcoma
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
干预措施: Vincristine (Drug)
Phase 2: Dose Expansion Ewing Sarcoma
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
干预措施: Pegfilgrastim (Biological)
Phase 2: Dose Expansion Ewing Sarcoma
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
干预措施: Filgrastim (Biological)
Phase 2: Dose Expansion DSRCT
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
干预措施: PEEL-224 (Drug)
Phase 2: Dose Expansion DSRCT
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
干预措施: Temozolomide (Drug)
Phase 2: Dose Expansion DSRCT
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
干预措施: Vincristine (Drug)
Phase 2: Dose Expansion DSRCT
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
干预措施: Pegfilgrastim (Biological)
Phase 2: Dose Expansion DSRCT
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
干预措施: Filgrastim (Biological)
Phase 2: Dose Expansion Other Sarcoma
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
干预措施: PEEL-224 (Drug)
Phase 2: Dose Expansion Other Sarcoma
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
干预措施: Temozolomide (Drug)
Phase 2: Dose Expansion Other Sarcoma
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
干预措施: Vincristine (Drug)
Phase 2: Dose Expansion Other Sarcoma
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
干预措施: Pegfilgrastim (Biological)
Phase 2: Dose Expansion Other Sarcoma
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
干预措施: Filgrastim (Biological)
结局指标
主要结局
Maximum Tolerated Dose (MTD) (Phase 1)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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).
次要结局
- Peak Time (Tmax) of PEEL-224(Days 1, 2, 3, and 8 of Cycle 1 (21 days per cycle))
- ctDNA Burden EWS Cohort at Day 8(Day 8)
- OS EWS Cohort(Up to 5 years (based on accrual duration of 2 years))
- OS DSRCT Cohort(Up to 5 years (based on accrual duration of 2 years))
- Median Progression-Free Survival (PFS) Other Sarcoma Cohort(Approximately 2 years)
- Objective Response Rate Other Sarcoma Cohort(Up to 5 years (based on accrual duration of 2 years))
- Overall Survival (OS) Other Sarcoma Cohort(Up to 5 years (based on accrual duration of 2 years))
- Median PFS EWS Cohort(Approximately 2 years)
- Area Under the Plasma Concentration Versus Time Curve (AUC) of PEEL-224(Days 1, 2, 3, and 8 of Cycle 1 (21 days per cycle))
- Median PFS DSRCT Cohort(Approximately 2 years)
- Circulating Tumor DNA (ctDNA) Burden EWS Cohort at Baseline(Baseline)
- ctDNA Burden DSRCT Cohort at Baseline(Baseline)
- ctDNA Burden DSRCT Cohort at Day 8(Day 8)
- Peak Plasma Concentration (Cmax) of PEEL-224(Days 1, 2, 3, and 8 of Cycle 1 (21 days per cycle))
- ≥ Grade 2 Treatment-Related Toxicity Rate (Phase 1)(Approximately 2 years)
- Median Duration of Stable Disease (Phase 2)(Approximately 2 years)
- ≥ Grade 2 Treatment-Related Toxicity Rate (Phase 2)(Approximately 2 years)
- Median Duration of Overall Response (DOR) (Phase 2)(Approximately 2 years)
- Median Duration of Complete Response (CR) (Phase 2)(Approximately 2 years)
研究者
David S Shulman, MD
Sponsor Investigator
Dana-Farber Cancer Institute