A Phase 2 Study of Abemaciclib in Patients With Brain Metastases Secondary to Hormone Receptor Positive Breast Cancer, Non-small Cell Lung Cancer, or Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 162
- 试验地点
- 23
- 主要终点
- Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Intracranial Response Rate (OIRR)
研究概览
简要总结
The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as abemaciclib in participants with hormone receptor positive breast cancer, non-small cell lung cancer (NSCLC), or melanoma that has spread to the brain.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have brain metastases secondary to hormone receptor positive breast cancer, NSCLC, or melanoma.
- •Have either human epidermal growth factor receptor 2 positive (HER2+) (Study Part A) or negative HER2- (Study Part B) breast cancer.
- •Participants in Study Part C must have HR+ breast cancer, NSCLC, or melanoma with brain lesions clinically indicated for surgical resection as well as consent to provide tissue for drug concentration determination after 5 to 14 days of study drug dosing.
- •Participants in Part D must have NSCLC of any subtype.
- •Participants in Part E must have melanoma of any subtype.
- •Participants in Part F must have HR+ breast cancer, NSCLC, or melanoma with leptomeningeal metastases.
- •For Parts A, B, D, and E: Must have at least 1 measurable brain lesion ≥10 millimeters (mm) in the longest diameter (LD).
- •For Part C (surgical): Have metastatic brain lesion(s) for which surgical resection is clinically indicated.
- •Have completed local therapy (surgical resection, whole-breast radiotherapy (WBRT), or SRS) ≥14 days prior to initiating abemaciclib and recovered from all acute effects.
- •If receiving concomitant corticosteroids, must be on a stable or decreasing dose for at least 7 days prior to the baseline Gd-MRI.
- •Have a Karnofsky performance status of ≥
- •Have a life expectancy ≥12 weeks.
- •For HR+ breast cancer participants in part A, B, C, and F: If currently receiving endocrine therapy, a participant may continue to receive the same endocrine therapy provided that extracranial disease is stable for at least 3 months and central nervous system (CNS) disease progression has occurred while on this endocrine therapy. If these conditions are not met, participants must discontinue endocrine therapy prior to initiation of abemaciclib.
- •For HER2+ breast cancer participants in parts A, C, and F: participants may receive concurrent treatment (ongoing or initiated simultaneously with abemaciclib) with IV trastuzumab.
- •For NSCLC participants in parts C, D, and F: if currently receiving gemcitabine or pemetrexed (single-agent or in combination with another therapy), a participant may continue to receive 1 of these 2 therapies provided that extracranial disease is stable for at least 6 weeks and CNS disease progression has occurred while on this therapy.
- •Have adequate organ function.
排除标准
- •Require immediate local therapy, including but not limited to WBRT, SRS, or surgical resection, for treatment of brain metastases.
- •Are taking concurrent enzyme-inducing antiepileptic drugs (EIAED).
- •Have evidence of significant (ie, symptomatic) intracranial hemorrhage.
- •For Parts A, B, C, D, E: Have evidence of leptomeningeal metastases. Note: discrete dural metastases are permitted.
- •Have experienced >2 seizures within 4 weeks prior to study entry.
- •For Parts A, B, D, E, and F: Have previously received treatment with any cyclin dependent kinase 6 (CDK6) inhibitor. For Part C participants may have received prior palbociclib or ribociclib, but not abemaciclib treatment.
- •Have known contraindication to Gd-MRI.
- •Have a preexisting chronic condition resulting in persistent diarrhea.
研究组 & 干预措施
Part A Abemaciclib: HR+, HER2+ Breast Cancer
Abemaciclib 200 milligram (mg) was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or in combination with endocrine therapy (ET). Participants with hormone receptor positive (HR+), HER2+ breast cancer receiving concurrent trastuzumab, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: Abemaciclib (Drug)
Part B Abemaciclib: HR+, HER2- Breast Cancer
Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants in combination with endocrine therapy (ET).
Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: Abemaciclib (Drug)
Part C Abemaciclib: Surgical Resection
Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants with breast cancer in combination with endocrine therapy (ET). Participants with HR+, HER2+ breast cancer, NSCLC, or melanoma with intracranial lesions for which surgical resection is clinically indicated receiving concurrent trastuzumab, gemcitabine, or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours for 5-14 days prior to surgical resection. Dosing may resume following wound healing on a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: Abemaciclib (Drug)
Part D Abemaciclib: Non-Small Cell Lung Cancer (NSCLC)
Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: Abemaciclib (Drug)
Part E Abemaciclib: Melanoma
Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: Abemaciclib (Drug)
Part F Abemaciclib: HR+ Breast Cancer, NSCLC, or Melanoma
Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants with breast cancer in combination with endocrine therapy (ET). Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received concurrent trastuzumab, gemcitabine, or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: Abemaciclib (Drug)
结局指标
主要结局
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Intracranial Response Rate (OIRR)
时间窗: Baseline to Objective Disease Progression (Up to 36 Months)
OIRR is the percentage of participants with a (CR) or (PR) based on the Response Assessment in Neuro-Oncology Brain Metastasis (RANO-BM) response criteria. CR is measurable target lesions, the disappearance of all central nervous system (CNS) target lesions for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. PR is at least a 30% decrease in the sum longest duration (LD) of CNS target lesions, taking as reference the baseline sum LD for at least 4 weeks; no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. Nontarget lesions requires disappearance CNS non-target lesions and no new CNS lesions. Stable disease (SD) is less than (\<)30% decrease relative to baseline but \<20% increase in sum LD relative to nadir. Progressive disease (PD) is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 millimeter (mm).
次要结局
- Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale(Baseline, Cycle 3 (Up to 63 Days))
- Duration of CR or PR: Duration of Intracranial Response (DOIR)(Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause (Up to 36 Months))
- Percentage of Participants With Best Overall Intracranial Response (BOIR) of CR, PR, or SD: Intracranial Disease Control Rate (IDCR)(Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months))
- Percentage of Participants With BOIR of CR, PR, or SD With Duration of SD for at Least 6 Months: Intracranial Clinical Benefit Rate (ICBR)(Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months))
- Percentage of Participants With a Best Overall Response of CR, PR, or SD: Extracranial Disease Control Rate (EDCR)(Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months))
- Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR)(Baseline to Earliest Objective Progression or Start of New Anticancer Therapy (Up to 36 Months))
- Overall Survival (OS)(Baseline to the Date of Death from Any Cause (Up to 5 Years))
- Percentage of Participants With a Best Response of CR or PR: Extracranial Objective Response Rate (EORR)(Baseline to Disease Progression (Up to 36 Months))
- Progression Free Survival (PFS) Bi-compartmental(Baseline to Objective Disease Progression or Death from Any Cause (Up to 36 Months))
- Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18)(Parts A, B, D, E, F, Cycle 3, Day 1: Predose; Part C, Cycle 4, Day 1: Predose)