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

Eli Lilly and Company0 个研究点目标入组 251 人开始时间: 2015年2月10日最近更新: 2020年6月22日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Eli Lilly and Company
入组人数: 251

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•Patients are eligible to be included in the study only if they meet all of
•the following criteria:
•[1] have brain metastases secondary to histologically or cytologically confirmed HR+ breast cancer, NSCLC, or melanoma.
•For Parts A and B: have confirmed HR+ breast cancer. To fulfill the
•requirement for HR+ disease, a breast cancer must express, at least 1 of
•the hormone receptors (ER or progesterone receptor [PgR]). For ER and PgR assays to be considered positive, =1% of tumor cell nuclei must be
•immunoreactive by immunohistochemistry (IHC) (Hammond et al.
•For Part A: have HR+ breast cancer with confirmed HER2
•overexpression (HER2+) status. To fulfill the requirement for HER2+
•disease, tumor tissue must demonstrate 3+ by IHC or gene amplification
•by in-situ hybridization (ISH) (Wolff et al. 2013).
•For Part B: have HR+ breast cancer which does not demonstrate HER2
•overexpression (HER2-) by either IHC or ISH.
•For Part C: have HR+ breast cancer, NSCLC, or melanoma with brain
•lesions for which surgical resection is clinically indicated and agree to
•provide posttreatment (5 to 14 days after initiating abemaciclib) brain
•tumor tissue.
•For Part D: have NSCLC of any subtype.
•For Part E: have melanoma of any subtype
•For Part F: have HR+ breast cancer, NSCLC, or melanoma with
•leptomeningeal metastases by documented positive CSF cytology or by
•clinical signs and symptoms associated with abnormal magnetic
•resonance imaging (MRI) features. Concomitant parenchymal brain
•metastases are allowed (not required), but must be stable for at least 4
•weeks following whole brain radiotherapy (WBRT) or stereotactic
•radiosurgery (SRS).
•[2] Deleted criterion.
•[3] For Parts A,B, D and E: have =1 new or not previously irradiated
•measurable metastatic brain lesion =10 mm in the longest diameter (LD) and =5 mm in
•the perpendicular plane or a progressive previously irradiated metastatic brain lesion on radiographic imaging by gadolinium-enhanced magnetic resonance imaging (Gd MRI).
•For Part C (surgical): have metastatic brain lesion(s) for which surgical
•resection is clinically indicated.
•[4] have completed local therapy (surgical resection or SRS) =
•14 days prior to initiating abemaciclib and recovered from all acute
•effects. Patients are not required to have received prior local therapy for
•study participation.
•[5] if receiving concomitant corticosteroids, must be on a stable or
•decreasing dose for at least 7 days prior to the baseline Gd-MRI.
•[6] have a Karnofsky performance status of =70 (see Attachment 4).
•[7] have a life expectancy =12 weeks.
•[8] for HR+ breast cancer patients in Parts A, B and F: if currently receiving endocrine therapy, a patient may continue to receive the same endocrine therapy provided that extracranial disease is stable for at least 3 months and CNS disease progression has occurred while on this
•endocrine therapy. If these conditions are not met, patients must discontinue endocrine therapy prior to initiation of abemaciclib. Part C patients may continue or initiate endocrine therapy concurrently with abemaciclib and need not meet the above conditions.
•For HER2+ breast cancer patients in Parts A, C, and F: patients may
•receive concurrent treatment (ongoing or initiated simultaneously with
•abemaciclib) with trastuzumab. Concurrent treatment with trastuzumab emtansine (T-DM1) is not allowed.
•For NSCLC patients in Parts D, and F: if currently receiving
•gemcitabine or pemetrexed (single-a

排除标准

•Patients will be excluded from the study if they meet any of the
•following criteria:
•[16] require immediate local therapy, including but not limited to
•WBRT, SRS, or surgical resection, for treatment of brain metastases.
•[17] require concurrent anticancer treatment at any time during the
•study treatment period.
•[18] are taking concurrent enzyme-inducing antiepileptic drugs
•[19] have evidence of significant (ie, symptomatic) intracranial
•hemorrhage.
•[20] for Parts A, B, C, D, and E: have evidence of leptomeningeal
•metastases by clinical signs and symptoms associated with abnormal
•MRI features or by documented CSF cytology.
•[21] have experienced >2 seizures within 4 weeks prior to study entry.
•[22] have visceral crisis. Visceral crisis is not the mere presence of
•visceral metastases but implies severe organ dysfunction as assessed by
•symptoms and signs, laboratory studies, and rapid progression of the
•[23] for Parts A, B, D, E, and F: have previously received treatment
•with any CDK4 and CDK6 inhibitor. Part C patients may have received
•prior palbociclib or ribociclib, but not abemaciclib, treatment.
•[24] have known contraindication to Gd-MRI.
•[25] deleted criterion.
•[26] are currently enrolled in a clinical trial involving an investigational
•product or nonapproved use of a drug or device (other than the study
•drug used in this study), or concurrently enrolled in any other type of
•medical research judged not to be scientifically or medically compatible
•with this study.
•[27] have received treatment with a drug that has not received regulatory approval for any indication within 14 days of the initial dose of abemaciclib.
•[28] have a personal history within the last 12 months of any
•ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation) or sudden cardiac arrest.
•[29] have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (for example, history of major surgical resection involving the stomach or small bowel).
•[30] have a preexisting chronic condition resulting in baseline Grade 2
•or higher diarrhea.
•[31] have a history of any other cancer (except nonmelanoma skin
•cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years.
•[32] are lactating.
•[33] have an active systemic fungal and/or known viral infection (for
•example, human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C antibodies). Screening is not required for enrollment.
•[34] have an acute bacterial infection requiring IV antibiotics.
•[35] have received recent (within 28 days of initial dose of abemaciclib) or concurrent yellow fever vaccination.

研究者

发起方

Eli Lilly and Company

相似试验

进行中（未招募）

1 期

A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer, Non-Small Cell Lung Cancer, or Melanoma That Has Spread to the Brai

EUCTR2014-004010-28-ATEli Lilly and Company247

进行中（未招募）

1 期

A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer That Has Spread to the BraiBrain tumours, Breast CancerMedDRA version: 18.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864

EUCTR2014-004010-28-FREli Lilly and Company120

进行中（未招募）

1 期

A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer, Non-Small Cell Lung Cancer, or Melanoma That Has Spread to the Brai

EUCTR2014-004010-28-ITELI LILLY & COMPANY, LILLY CORPORATE CENTER162

进行中（未招募）

1 期

A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer, Non-Small Cell Lung Cancer, or Melanoma That Has Spread to the BraiBrain tumors, Breast CancerMedDRA version: 18.1Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864

EUCTR2014-004010-28-ESilly S.A.247

进行中（未招募）

1 期

EUCTR2019-002931-27-BEEli Lilly and Company60