A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer, Non-Small Cell Lung Cancer, or Melanoma That Has Spread to the Brai
- Conditions
- Brain tumours, Breast Cancer, Non-Small Cell Lung Cancer, MelanomaMedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000020826Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-004010-28-BE
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 251
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.
2010).
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
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
(EIAED).
[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
disease.
[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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method