A Randomized, Open-Label, Phase 2 Study Evaluating Abemaciclib in Combination With Irinotecan and Temozolomide in Participants With Relapsed or Refractory Ewing's Sarcoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 46
- 试验地点
- 28
- 主要终点
- Progression Free Survival (PFS) Assessed by Blinded Independent Review Committee (BIRC) by Bayesian Analysis
研究概览
简要总结
The purpose of this study is to measure the benefit of adding abemaciclib to chemotherapy (irinotecan and temozolomide) for Ewing's sarcoma that has come back or did not respond to treatment. This trial is part of the CAMPFIRE master protocol, which is a platform to speed development of new treatments for children and young adults with cancer. Your participation in this trial could last 11 months or longer, depending on how you and your tumor respond.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 39 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Ewing's sarcoma or Ewing's sarcoma-like tumor by institutional pathologist. The original pathological report is required. Repeat biopsy at progression is not required
- •Refractory disease or confirmed radiological progression or recurrence following first or later line of treatment of Ewing's sarcoma or Ewing's sarcoma-like tumor
- •-- Must have one measurable or evaluable lesion per RECIST 1.1
- •Adequate performance status based on age
- •For participants less than (<)16 years of age, a Lansky score greater than or equal to (≥)50, or
- •For participants ≥16 years of age, a Karnofsky score ≥50
- •Participants must have discontinued all previous treatments for cancer or investigational agents ≥7 days after the last dose and must have recovered from the acute effects
- •Adequate hematologic and organ function less than or equal to (≤)14 days prior to Day 1 of Cycle 1:
- •Absolute neutrophil count ≥1000/microliter (µL)
- •Platelets ≥75,000/cubic millimeter (mm³)
- •Hemoglobin ≥8 grams per deciLiter (g/Dl) (≥100 grams per Liter [g/L])
- •Total bilirubin ≤1.5 times (×) upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN
- •Creatinine clearance or calculated glomerular filtration rate (GFR) ≥60 milliliters per minute per square meter (Ml/min/m²) or serum creatinine based on age/gender
- •Female participants of childbearing potential must have a negative urine or serum pregnancy test
- •Body weight ≥10 kilograms (kg)
- •Must be able to swallow and/or have a gastric/nasogastric tube
- •-- Participants in the European Union must be able to swallow intact capsules
- •Stable or decreasing dose of steroids at least 7 days prior to enrollment
- •Life expectancy of at least 8 weeks and able to complete at least 1 cycle of treatment
- •Participants/caregivers are able and willing to make themselves available for the duration of the study and are willing to follow study procedures, including adherence to the pharmacokinetic (PK) sampling schedule
排除标准
- •Participants with severe and/or uncontrolled concurrent medical disease or psychiatric illness/social situation that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol
- •Participants with an active fungal, bacterial, and/or known severe viral infection including, but not limited to, human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis.
- •Participants who have had allogeneic bone marrow or solid organ transplant
- •Surgery: Participants who have had, or are planning to have, the following invasive procedures:
- •Major surgical procedure, laparoscopic procedure, or significant traumatic injury within 28 days prior to enrollment
- •Surgical or other wounds must be adequately healed prior to enrollment
- •Female participants who are pregnant or breastfeeding
- •Have received any prior cyclin-dependent kinase (CDK) 4 and 6 inhibitor
- •Progression during prior treatment with irinotecan and/or temozolomide
- •Have a known intolerability or hypersensitivity to any of the study treatments or dacarbazine
- •Diagnosed and/or treated additional malignancy within 3 years prior to enrollment
研究组 & 干预措施
Abemaciclib + Irinotecan +Temozolomide
Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met.
- Abemaciclib: 55 mg/m² (milligrams per square meter), administered orally twice daily (BID) for less than (<18) years or 100 mg administered orally BID for greater than or equal to (≥)18 years.
- Irinotecan: 50 mg/m²/day, administered intravenously (IV) on Days 1-5 of each cycle.
- Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.
干预措施: Irinotecan (Drug)
Abemaciclib + Irinotecan +Temozolomide
Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met.
- Abemaciclib: 55 mg/m² (milligrams per square meter), administered orally twice daily (BID) for less than (<18) years or 100 mg administered orally BID for greater than or equal to (≥)18 years.
- Irinotecan: 50 mg/m²/day, administered intravenously (IV) on Days 1-5 of each cycle.
- Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.
干预措施: Abemaciclib (Drug)
Abemaciclib + Irinotecan +Temozolomide
Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met.
- Abemaciclib: 55 mg/m² (milligrams per square meter), administered orally twice daily (BID) for less than (<18) years or 100 mg administered orally BID for greater than or equal to (≥)18 years.
- Irinotecan: 50 mg/m²/day, administered intravenously (IV) on Days 1-5 of each cycle.
- Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.
干预措施: Temozolomide (Drug)
Irinotecan +Temozolomide
Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met.
- Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle.
- Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.
干预措施: Irinotecan (Drug)
Irinotecan +Temozolomide
Participants received the following treatments in a 21-day cycle, continuing until disease progression, unacceptable toxicity, or a criterion for discontinuation was met.
- Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle.
- Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.
干预措施: Temozolomide (Drug)
结局指标
主要结局
Progression Free Survival (PFS) Assessed by Blinded Independent Review Committee (BIRC) by Bayesian Analysis
时间窗: From Date of Randomization until Disease Progression or Death Due to Any Cause (Up to 22.36 months)
PFS was defined as the time from randomization until the first occurrence of documented disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria, or death from any cause in absence of progressive disease, whichever came first. Progressive disease (PD) was defined as at least 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 millimeter (mm), or unequivocal progression of non-target lesions, or 1 or more new lesions. An event was considered when tumor progression or death occurred, with event date being the earliest date of PD or death. Participants known to be alive and without tumor progression were censored at date of their last adequate tumor assessment per RECIST v1.1 criteria, or date of randomization (whichever was later). Results were obtained using Bayesian analysis and are reported as posterior mean along with its 80% credible interval.
PFS Assessed by BIRC by Frequentist Analysis
时间窗: From Date of Randomization until Disease Progression or Death Due to Any Cause (Up to 22.36 months)
PFS was defined as the time from randomization until the first occurrence of documented disease progression per RECIST v1.1 criteria, or death from any cause in absence of progressive disease, whichever came first. PD was defined as at least 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. An event was considered when tumor progression or death occurred, with the event date being the earliest date of PD or death. Participants known to be alive and without tumor progression were censored at the date of their last adequate tumor assessment per RECIST v1.1 criteria, or date of randomization (whichever was later). Results were obtained using frequentist analysis.
次要结局
- PFS Assessed by Investigator by Bayesian Analysis(From Date of Randomization until Disease Progression or Death Due to Any Cause (Up to 22.39 Months))
- PFS Assessed by Investigator by Frequentist Analysis(From Date of Randomization until Disease Progression or Death Due to Any Cause (Up to 22.39 Months))
- Overall Survival (OS)(From Date of Randomization until Death Due to Any Cause (Up to 26.37 months))
- Overall Response Rate (ORR): Percentage of Participants Who Achieved a Complete Response (CR) or Partial Response (PR) Assessed by BIRC(From Date of Randomization until Disease Progression, Death Due to Any Cause, Concomitant Radiotherapy/Surgery, or Start of New Anti-Cancer Therapy (Up to 22.36 Months))
- ORR: Percentage of Participants Who Achieved a CR or PR Assessed by Investigator(From Date of Randomization until Disease Progression, Death Due to Any Cause, Concomitant Radiotherapy/Surgery, or Start of New Anti-Cancer Therapy (Up to 22.39 Months))
- Duration of Response (DoR) Assessed by BIRC(From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up to 10.7 Months))
- DoR Assessed by Investigator(From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up to 12.7 Months))
- Percentage of Participants With a Best Overall Response of CR, PR, Stable Disease (SD) or Non-CR/Non-PD: Disease Control Rate (DCR) Assessed by BIRC(From Date of Randomization until Disease Progression, or Death Due to Any Cause, Concomitant Radiotherapy/Surgery, or Start of New Anti-Cancer Therapy (Up to 22.36 Months))
- Percentage of Participants With a Best Overall Response of CR, PR or SD: DCR Assessed by Investigator(From Date of Randomization until Disease Progression, or Death Due to Any Cause, Concomitant Radiotherapy/Surgery, or Start of New Anti-Cancer Therapy (Up to 22.39 Months))
- Pharmacokinetics (PK): Minimum Plasma Concentration (Cmin) of Abemaciclib(Pre-dose on Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1; End of irinotecan infusion on Cycle 2 Day 1 and Cycle 4 Day 1)
- Abemaciclib Product Acceptability(Day 1 of Cycle 1 through Cycle 3 (21-day cycles))