A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer That Has Spread to the Brai

Phase 1

• Conditions: Brain tumours, Breast Cancer; MedDRA version: 18.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-004010-28-FR
• Lead Sponsor: Eli Lilly and Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-08-19
• Last Update Posted: 3 August 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 120

Inclusion Criteria

Patients are eligible to be included in the study only if they meet all of the following criteria:
[1] have histologically confirmed HR+ metastatic 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)
[2] For Part A: have 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). For Part B: have disease which does not demonstrate HER2 overexpression (HER2-) by either IHC or ISH. For Part C (surgical): have either HER2+ or HER2- status with brain lesion(s) for which surgical resection is clinically indicated and agree to provide posttreatment (5 to 14 days after initiating abemaciclib) brain tumor tissue.
[3] For Parts A and B: have =1 new or not previously irradiated measurable metastatic brain lesion =10 mm in the longest diameter (LD) or a progressive previously irradiated metastatic brain lesion on radiographic imaging by gadolinium-enhanced magnetic resonance imaging (Gd MRI). Note: for patients with prior WBRT or SRS, previously irradiated lesion(s) must demonstrate unequivocal progression on baseline Gd MRI in the opinion of the investigator. Otherwise new or not previously irradiated lesions must be present. For Part C (surgical): have 1 to 3 metastatic brain lesion(s) for which surgical resection is clinically indicated.
[4] have completed local therapy (surgical resection, WBRT, 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
[7] have a life expectancy =12 weeks.
[8] 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 intracranial 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.
[9] have discontinued all previous therapies for cancer (including cytotoxic chemotherapy, targeted therapy [including, but not limited to, everolimus], radiotherapy, immunotherapy, and investigational therapy) for at least 14 days prior to receiving abemaciclib and recovered from the acute effects of therapy (treatment related toxicity resolved to baseline) except for residual alopecia or peripheral neuropathy. Note: patients currently receiving trastuzumab and receiving clinical benefit may continue to receive trastuzumab throughout the study. Concurrent treatment with trastuzumab emtansine (T-DM1) is not allowed.

[10] for patients receiving concurrent trastuzumab, must have left ventricular ejection fraction within investigative site’s normal range.
[11] have adequate organ function including:
• Hematologic: Absolute neutrophil count (ANC) = 1.5 x 109/L, platelets = 100 x 109/L, and hemoglobin = 8 g/dL. Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion

Exclusion Criteria

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. Note: exceptions are endocrine therapy, trastuzumab (HER2+ patients), or surgical resection (Part C patients only).
[18] are taking concurrent enzyme-inducing antiepileptic drugs (EIAED).
[19] have evidence of significant (ie, symptomatic) intracranial hemorrhage.
[20] have evidence of leptomeningeal metastases on brain Gd-MRI or by previously documented CSF cytology. Note: discrete dural metastases are permitted.
[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] have previously received treatment with any CDK4/6 inhibitor.
[24] have known contraindication to Gd-MRI.
[25] are currently receiving lapatinib.
[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 intravenous 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