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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02308020
• Other study ID #: 15450
• Secondary ID: I3Y-MC-JPBO2014-
• Status: Completed
• Phase: Phase 2
• Start date: April 20, 2015
• Est. completion date: November 8, 2019

Study information

• Verified date: December 2020
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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, non-small cell lung cancer (NSCLC), or melanoma that has spread to the brain.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 162
• Est. completion date: November 8, 2019
• Est. primary completion date: November 8, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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 =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 (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.

Related Conditions & MeSH terms

• Brain Metastases
• Breast Cancer
• Breast Neoplasms
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Melanoma
• Neoplasm Metastasis
• Non-small Cell Lung Cancer

Intervention

Drug:
• Abemaciclib
Administered orally

Locations

Country	Name	City	State
Australia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nedlands
Australia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Newcastle
Australia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Southport
Australia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Woolloongabba
Austria	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Wien
Belgium	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Brussel
Belgium	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Charleroi
Belgium	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Leuven
Belgium	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Liege
Canada	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Ottawa
France	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lille
France	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lille Cedex
France	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lyon Cedex 08
France	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Paris Cedex 05
France	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Saint-Brieuc
France	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Toulouse cedex 9
Israel	Hadassah Medical Center - Ein Karem	Jerusalem
Israel	Sheba Medical Center	Tel Hashomer
Italy	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cona
Italy	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Genova
Italy	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Padova
Italy	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Roma
Spain	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Barcelona
Spain	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Madrid
Spain	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sevilla
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado	Aurora	Colorado
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	City of Hope National Medical Center	Duarte	California
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Kaiser Permanente Center for Health Research	Honolulu	Hawaii
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of California - San Diego	La Jolla	California
United States	James Graham Brown Cancer Center	Louisville	Kentucky
United States	SMO Sarah Cannon Research Inst.	Nashville	Tennessee
United States	Tennessee Oncology PLLC	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Providence Health and Services	Portland	Oregon
United States	Washington University Medical Center	Saint Louis	Missouri
United States	Univ of California San Francisco	San Francisco	California
United States	John Wayne Cancer Institute	Santa Monica	California
United States	H Lee Moffitt Cancer Center	Tampa	Florida
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  France,  Israel,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Intracranial Response Rate (OIRR)	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).	Baseline to Objective Disease Progression (Up to 36 Months)
Secondary	Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR)	Percentage of Participants with BOIR was categorized as CR, PR, SD, PD or NE, as defined by RANO-BM, from baseline until the earliest of objective progression according to brain metastases response criteria or start of new anticancer therapy. CR is measurable target lesions, the disappearance of all 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 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. SD is <30% decrease relative to baseline but <20% increase in sum LD relative to nadir. 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 mm. NE is absent (no abnormality; normal), or non-evaluable (NE).	Baseline to Earliest Objective Progression or Start of New Anticancer Therapy (Up to 36 Months)
Secondary	Duration of CR or PR: Duration of Intracranial Response (DOIR)	DOIR is measured from the date of first evidence of a confirmed response (CR or PR), as defined by RANO-BM, to the date objective progression or death from any cause. CR is measurable target lesions, the disappearance of all 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 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. Participants who have neither progressed nor died were censored on the day of their last radiographic tumor assessment or on the date of response. 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 mm. DOIR was summarized using Kaplan-Meier estimates.	Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause (Up to 36 Months)
Secondary	Percentage of Participants With Best Overall Intracranial Response (BOIR) of CR, PR, or SD: Intracranial Disease Control Rate (IDCR)	Percentage of participants with BOIR of CR, PR, or SD: IDCR, as defined by RANO-BM is reported. 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 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. SD is less than (<)30% decrease relative to baseline but <20% increase in sum LD relative to nadir. 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 mm.	Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months)
Secondary	Percentage of Participants With BOIR of CR, PR, or SD With Duration of SD for at Least 6 Months: Intracranial Clinical Benefit Rate (ICBR)	ICBR is the percentage of participants with BOIR of CR, PR, or SD with duration of SD for at least 6 months, as defined by RANO-BM. CR is measurable target lesions, the disappearance of all 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 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. SD is <30% decrease relative to baseline but <20% increase in sum LD relative to nadir. 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 mm.	Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months)
Secondary	Overall Survival (OS)	OS was measured from baseline to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for a particular analysis, OS was censored for that analysis at the date of last contact prior to the data inclusion cutoff date (contacts considered in the determination of last contact date include adverse event (AE) date, tumor assessment date, visit date, and last known alive date). OS was summarized using Kaplan-Meier estimates.	Baseline to the Date of Death from Any Cause (Up to 5 Years)
Secondary	Percentage of Participants With a Best Response of CR or PR: Extracranial Objective Response Rate (EORR)	The percentage of participants with a best response of CR or PR objective response rate is complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1) guidelines. CR is disappearance of all target and non-target lesions; PR is =30% decrease in sum of longest diameter of target lesions. PD is defined as at least a 20% increase in the sum LD of CNS target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) and the 20% increase must be at least one lesion must increase by an absolute value of =5 mm to be considered progression.	Baseline to Disease Progression (Up to 36 Months)
Secondary	Percentage of Participants With a Best Overall Response of CR, PR, or SD: Extracranial Disease Control Rate (EDCR)	Disease control rate (DCR) (CR+ PR+ SD) per RECIST v1.1. is defined as the percentage of participants with best overall response of CR, PR, or SD. CR is disappearance of all target and non-target lesions; PR is =30% decrease in sum of longest diameter of target lesions. PD is defined as at least a 20% increase in the sum LD of CNS target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) and the 20% increase must be at least one lesion must increase by an absolute value of =5 mm to be considered progression.	Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months)
Secondary	Progression Free Survival (PFS) Bi-compartmental	PFS was measured from baseline to objective progression (intracranial or extracranial) as defined by (RANO-BM.) or death from any cause. Participants who have neither progressed nor died were censored at the day of their last radiographic tumor assessment. 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 mm. PFS was summarized using Kaplan-Meier estimates.	Baseline to Objective Disease Progression or Death from Any Cause (Up to 36 Months)
Secondary	Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale	The MDASI-BT is an instrument to assess multi-symptoms in participants with brain tumor metastases (including those with brain metastases secondary to breast cancer). The MDASI-BT of participants with a change from baseline is reported as mean core symptoms, mean brain tumor symptoms, and symptom groupings (mean focal neurologic deficit, mean generalized/disease status symptoms, and mean gastrointestinal symptoms). The mean of all symptom subscale items was calculated where 0 equals "not present" and 10 equals "as bad as you can imagine." A change from baseline with negative values indicate improvement, positive values indicate worsening.	Baseline, Cycle 3 (Up to 63 Days)
Secondary	Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18)	A PK plasma sample was taken prior to abemaciclib dose to analyze the minimum concentrations of abemaciclib and its metabolites (Cmin) - Individual Cmin values were averaged if there were 3 or more available data points, otherwise individual data are reported.	Parts A, B, D, E, F, Cycle 3, Day 1: Predose; Part C, Cycle 4, Day 1: Predose