临床试验/NCT05734066

NCT05734066

招募中

1 期

A Phase 1/2, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Recommended Phase 2 Dose (RP2D), and Efficacy of Lurbinectedin Monotherapy in Pediatric Participants With Previously Treated Solid Tumors Followed by Expansion to Assess Efficacy and Safety in Pediatric and Young Adult Participants With Relapsed/Refractory Ewing Sarcoma.

Jazz Pharmaceuticals15 个研究点分布在 2 个国家目标入组 60 人2023年5月23日

适应症Refractory Ewing Sarcoma Relapsed Ewing Sarcoma Ewing Sarcoma

干预措施Lurbinectedin

概览

阶段: 1 期
干预措施: Lurbinectedin
疾病 / 适应症: Refractory Ewing Sarcoma
发起方: Jazz Pharmaceuticals
入组人数: 60
试验地点: 15
主要终点: Phase 1: Number of Participants Experiencing Dose-limiting Toxicities (DLTs)
状态: 招募中
最后更新: 2个月前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

This study is conducted in two phases. The phase 1 portion of the study evaluates the safety, tolerability, pharmacokinetics (PK), recommended phase 2 dose (RP2D), and effectiveness of lurbinectedin monotherapy in pediatric participants with previously treated solid tumors. This is followed by the phase 2 portion, to further assess the effectiveness and safety in pediatric and young adult participants with recurrent/refractory Ewing sarcoma.

注册库

clinicaltrials.gov

开始日期

2023年5月23日

结束日期

2028年4月20日

最后更新

2个月前

研究类型

Interventional

研究设计

Sequential

性别

All

研究者

发起方

Jazz Pharmaceuticals

责任方

Sponsor

入排标准

入选标准

•Participant must meet the following age requirements at the time the informed consent form (ICF) (and assent form, if applicable) is signed:
•Phase 1 Part 1: participants must be ≥ 2 to \< 18 years of age.
•Phase 1 Part 2: participants must be ≥ 2 to ≤ 30 years of age.
•Phase 2: participants must be ≥ 2 to ≤ 30 years of age.
•Type of Participant and Disease Characteristics
•Participant has a confirmed solid tumor
•The participant has a Lansky/Karnofsky performance status score of ≥ 50%.
•The participant has adequate liver function, evidenced by the following laboratory values:
•Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN).
•Total bilirubin ≤ 1.5 × institutional ULN (with the exception of participants with Gilbert's syndrome who must have bilirubin \< 3 × institutional ULN).

排除标准

•Medical Conditions
•corrected QT interval (QTc) prolongation defined as a QTc ≥ 460 ms using the Bazett formula in age \< 18 years and QTc ≥ 470 ms using the Bazett formula in age ≥ 18 years.
•Known symptomatic Central nervous system (CNS) metastases requiring steroids. Participants with previously diagnosed CNS metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to enrollment, have discontinued high dose steroid treatment for these metastases for at least 2 weeks, and are neurologically stable (physiologic doses of steroids and short courses of steroids for other indications are acceptable).
•Persisting toxicity related to prior therapy; however, alopecia, sensory neuropathy, hypothyroidism, and rash Grade ≤ 2 are acceptable, and other Grade ≤ 2 adverse events (AEs) not constituting a safety risk based on the investigator's judgement are acceptable.
•An uncontrolled intercurrent illness including but not limited to ongoing or active infection requiring antibiotic, antifungal, or antiviral therapy, symptomatic heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
•Any other major illness that, in the investigator's judgment, could substantially increase the risk associated with participation in this study.
•Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high-risk for treatment complications.
•Prior/Concomitant Therapy
•Received prior treatment with lurbinectedin or trabectedin.
•Received prior treatment with any investigational product within 4 weeks of first infusion of study intervention. Observational studies are permitted.

研究组 & 干预措施

Phase 1 Part 1: Dose Selection

Pediatric participants ≥ 2 to \< 18 years of age with previously treated solid tumors of any histology at 5 dose levels to determine the RP2D, followed by a safety expansion cohort. Participants aged ≥ 6 to \< 18 years will be enrolled at the starting dose of 3.2 mg/m\^2 lurbinectedin. If, after review, the starting dose of 3.2 mg/m\^2 lurbinectedin Q3W is deemed safe in participants aged ≥ 6 to \< 18 years, participants aged ≥ 2 to \< 6 years may enroll and start at the dose as determined by the DMC. After this, the study opens to all participants (aged ≥ 2 to \< 18 years) for all dose levels. Upon completion of the cohort at all dose levels, participants may be eligible to enroll in a safety expansion cohort.

干预措施: Lurbinectedin

Phase 1 Part 2: RP2D

Participants aged ≥ 2 to ≤ 30 years with recurrent/refractory Ewing sarcoma at the RP2D to assess safety and efficacy signals.

干预措施: Lurbinectedin

Phase 2

If a signal of efficacy is observed in Phase 1 Part 2, additional participants aged ≥ 2 to ≤ 30 years with recurrent/refractory Ewing sarcoma will be enrolled. Phase 2 will further assess the safety and efficacy of lurbinectedin monotherapy.

干预措施: Lurbinectedin

结局指标

主要结局

Phase 1: Number of Participants Experiencing Dose-limiting Toxicities (DLTs)

时间窗: From the first dose through end of Cycle 1 (21 days).

Phase 2: Objective Response Rate (ORR) Based on Investigator Assessment (IA)

时间窗: Day -28 up to a total of 13 months postdose.

Phase 1: Number of Participants Experiencing Serious Adverse Events (SAEs) and Treatment Emergent Adverse Events (TEAEs)

时间窗: Post-baseline (Day 1) up to approximately 31 months.

Phase 1: Number of Participants With Dose Modifications

时间窗: Post-baseline (Day 1) up to approximately 31 months.

Phase 1: Number of Participants Who Discontinued Study Intervention Due to TEAEs

时间窗: Post-baseline (Day 1) up to approximately 31 months.

次要结局

Phase 1: Progression-Free Survival (PFS) Based on Investigator Assessment (IA)(Day -28 up to a total of 31 months postdose.)
Phase 1: Clinical Benefit Rate (CBR) With Stable Disease (SD) for At Least 12 Weeks(Day -28 up to a total of 31 months postdose.)
Phase 1: Overall Survival (OS)(Post-baseline (Day 1) up to 31 months postdose.)
Phase 1: Objective Response Rate (ORR) Based on Investigator Assessment (IA)(Day -28 up to a total of 31 months postdose.)
Phase 1: Duration of Response (DOR) in Participants with Confirmed Complete Response (CR) or Partial Response (PR)(Day -28 up to a total of 31 months postdose.)
Phase 1: Disease Control Rate (DCR)(Day -28 up to a total of 31 months postdose.)
Phase 2: Plasma Concentration of Lurbinectedin(Day 1: Predose up to approximately 168 hours postdose; Days 16, 31, 46: Predose up to approximately 5 minutes postdose.)
Phase 1: Plasma Concentration of Lurbinectedin(Day 1: Predose up to approximately 168 hours postdose; Days 16, 31, 46: Predose up to approximately 5 minutes postdose.)
Phase 1: Change From Baseline in Respiratory Rate(Post-baseline (Day 1) up to approximately 31 months.)
Phase 1: Change From Baseline in Pulse Rate(Post-baseline (Day 1) up to approximately 31 months.)
Phase 1: Change From Baseline in Blood Pressure(Post-baseline (Day 1) up to approximately 31 months.)
Phase 1: Change From Baseline in Weight(Post-baseline (Day 1) up to approximately 31 months.)
Phase 1: Change from Baseline in Platelet Count(Post-baseline (Day 1) up to approximately 31 months.)
Phase 1: Change from Baseline in Red Blood Cell Count(Post-baseline (Day 1) up to approximately 31 months.)
Phase 1: Change from Baseline in Hemoglobin(Post-baseline (Day 1) up to approximately 31 months.)
Phase 1: Change from Baseline in Differential White Blood Cell Count(Post-baseline (Day 1) up to approximately 31 months.)
Phase 1: Change From Baseline in AST/ALT Levels(Post-baseline (Day 1) up to approximately 31 months.)
Phase 1: Change From Baseline in Creatinine Levels(Post-baseline (Day 1) up to approximately 31 months.)
Phase 1: Change From Baseline in CPK Levels(Post-baseline (Day 1) up to approximately 31 months.)
Phase 2: Number of Participants Experiencing Serious Adverse Events (SAEs) and Treatment-emergent Adverse Events (TEAEs)(Post-baseline (Day 1) up to approximately 13 months.)
Phase 2: Number of Participants With Dose Modifications(Post-baseline (Day 1) up to approximately 13 months.)
Phase 2: Number of Participants Who Discontinued Study Intervention Due to TEAEs(Post-baseline (Day 1) up to approximately 13 months.)
Phase 2: Progression-Free Survival (PFS) Based on IA(Day -28 up to a total of 13 months postdose.)
Phase 2: Duration of Response (DOR) in Participants with Confirmed Complete Response (CR) or Partial Response (PR)(Day -28 up to a total of 13 months postdose.)
Phase 2: Disease Control Rate (DCR)(Day -28 up to a total of 13 months postdose.)
Phase 2: Clinical Benefit Rate (CBR) With Stable Disease (SD) for At Least 12 Weeks(Day -28 up to a total of 13 months postdose.)
Phase 2: Overall Survival (OS)(Post-baseline (Day 1) up to 13 months postdose.)
Phase 2: Change From Baseline in Respiratory Rate(Post-baseline (Day 1) up to approximately 13 months.)
Phase 2: Change From Baseline in Pulse Rate(Post-baseline (Day 1) up to approximately 13 months.)
Phase 2: Change From Baseline in Blood Pressure(Post-baseline (Day 1) up to approximately 13 months.)
Phase 2: Change From Baseline in Weight(Post-baseline (Day 1) up to approximately 13 months.)
Phase 2: Change From Baseline in Platelet Count(Post-baseline (Day 1) up to approximately 13 months.)
Phase 2: Change From Baseline in Red Blood Cell Count(Post-baseline (Day 1) up to approximately 13 months.)
Phase 2: Change From Baseline in Hemoglobin(Post-baseline (Day 1) up to approximately 13 months.)
Phase 2: Change From Baseline in Differential White Blood Cell Count(Post-baseline (Day 1) up to approximately 13 months.)
Phase 2: Change From Baseline in AST/ALT Levels(Post-baseline (Day 1) up to approximately 13 months.)
Phase 2: Change From Baseline in Creatinine Levels(Post-baseline (Day 1) up to approximately 13 months.)
Phase 2: Change From Baseline in CPK Levels(Post-baseline (Day 1) up to approximately 13 months.)