Clinical Trial 18093

Cancer Type: Neurologic Oncology
Interventions:Abemaciclib; LY2835219 (Abemaciclib)

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Solmaz Sahebjam

Overview

Study Title

A Phase 2 Study of Abemaciclib in Patients with Brain Metastases Secondary to Hormone Receptor Positive Breast Cancer

Summary

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 that has spread to the brain.

Objective

Primary Objective To evaluate abemaciclib with respect to objective intracranial response rate (OIRR; complete response [CR] + partial response [PR]) based on tumor assessments and brain metastases response criteria (see Attachment 5): - In women with brain metastases secondary to HR+, HER2+ breast cancer. - In women with brain metastases secondary to HR+, HER2- breast cancer. Secondary Objectives The secondary objectives of the study are as follows: To evaluate abemaciclib with respect to: - Intracranial disease per brain metastases response criteria - Best overall intracranial response (BOIR) - Duration of intracranial response (DOIR) (CR + PR) - Intracranial disease control rate (IDCR) (CR + PR + stable disease [SD]) - Intracranial clinical benefit rate (ICBR) (CR + PR + SD >/= 6 months) - Overall - OS - Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 and brain metastases response criteria - Disease control rate (DCR) (CR+ PR+ SD) per RECIST v1.1 and brain metastases response criteria - Progression-free survival (PFS) per RECIST v1.1 and brain metastases response criteria - Change in symptoms as assessed by MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) - Safety and tolerability - PK of abemaciclib and its metabolites Exploratory Objectives - To explore change in neurocognitive function as assessed by Trail Making Tests A and B - To explore change in neurologic signs as assessed by the Neurologic Assessment in euro-Oncology (NANO) scale - To explore the concentration of abemaciclib and its metabolites in plasma, cerebrospinal fluid (CSF), and brain tumor tissue collected at the time of surgical resection for patients participating in Part C, as well as patients in Parts A and B with progressive disease (PD)and planned surgical resection. - To explore biomarkers related to the mechanism of action of abemaciclib, the cell cycle,and/or the pathogenesis of breast cancer.

Inclusion Criteria

  • Have brain metastases secondary to hormone receptor positive breast cancer, non-small cell lung cancer (NSCLC), or melanoma.
  • Have either human epidermal growth factor receptor 2 positive (HER2+) (Study Part A) or 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, 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 ≥70.
  • 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.

  • Exclusion Criteria

  • 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 (i.e., 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.