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

Primary Purpose

Breast Cancer, Non-small Cell Lung Cancer, Melanoma

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Abemaciclib

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

City of Hope National Medical Center
University of California - San Diego
Univ of California San Francisco
John Wayne Cancer Institute
University of Colorado
Georgetown University Medical Center
Florida Cancer Specialists
H Lee Moffitt Cancer Center
Kaiser Permanente Center for Health Research
James Graham Brown Cancer Center
Dana Farber Cancer Institute
University of Michigan
Washington University Medical Center
Memorial Sloan Kettering Cancer Center
University of North Carolina at Chapel Hill
Providence Health and Services
SMO Sarah Cannon Research Inst.
Tennessee Oncology PLLC
University of Texas MD Anderson Cancer Center
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Hadassah Medical Center - Ein Karem
Sheba Medical Center
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.
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.
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.
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.
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.
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.
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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

Part A Abemaciclib: HR+, HER2+ Breast Cancer

Part B Abemaciclib: HR+, HER2- Breast Cancer

Part C Abemaciclib: Surgical Resection

Part D Abemaciclib: Non-Small Cell Lung Cancer (NSCLC)

Part E Abemaciclib: Melanoma

Part F Abemaciclib: HR+ Breast Cancer, NSCLC, or Melanoma

Arm Description

Abemaciclib 200 milligram (mg) was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or in combination with endocrine therapy (ET). Participants with hormone receptor positive (HR+), HER2+ breast cancer receiving concurrent trastuzumab, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants in combination with endocrine therapy (ET). Participants may continue to receive treatment until discontinuation criteria are met.

Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants with breast cancer in combination with endocrine therapy (ET). Participants with HR+, HER2+ breast cancer, NSCLC, or melanoma with intracranial lesions for which surgical resection is clinically indicated receiving concurrent trastuzumab, gemcitabine, or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours for 5-14 days prior to surgical resection. Dosing may resume following wound healing on a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants with breast cancer in combination with endocrine therapy (ET). Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received concurrent trastuzumab, gemcitabine, or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT02308020

First Posted

December 2, 2014

Last Updated

December 17, 2020

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT02308020

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Completed

Study Start Date

April 20, 2015 (Actual)

Primary Completion Date

November 8, 2018 (Actual)

Study Completion Date

November 8, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer, Non-small Cell Lung Cancer, Melanoma, Brain Metastases

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

162 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A Abemaciclib: HR+, HER2+ Breast Cancer

Arm Type

Experimental

Arm Description

Arm Title

Part B Abemaciclib: HR+, HER2- Breast Cancer

Arm Type

Experimental

Arm Description

Arm Title

Part C Abemaciclib: Surgical Resection

Arm Type

Experimental

Arm Description

Arm Title

Part D Abemaciclib: Non-Small Cell Lung Cancer (NSCLC)

Arm Type

Experimental

Arm Description

Arm Title

Part E Abemaciclib: Melanoma

Arm Type

Experimental

Arm Description

Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Arm Title

Part F Abemaciclib: HR+ Breast Cancer, NSCLC, or Melanoma

Arm Type

Experimental

Arm Description

Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants with breast cancer in combination with endocrine therapy (ET). Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received concurrent trastuzumab, gemcitabine, or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Intervention Type

Drug

Intervention Name(s)

Abemaciclib

Other Intervention Name(s)

LY2835219

Intervention Description

Administered orally

Primary Outcome Measure Information:

Title

Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Intracranial Response Rate (OIRR)

Description

Time Frame

Baseline to Objective Disease Progression (Up to 36 Months)

Secondary Outcome Measure Information:

Title

Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR)

Description

Time Frame

Baseline to Earliest Objective Progression or Start of New Anticancer Therapy (Up to 36 Months)

Title

Duration of CR or PR: Duration of Intracranial Response (DOIR)

Description

Time Frame

Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause (Up to 36 Months)

Title

Percentage of Participants With Best Overall Intracranial Response (BOIR) of CR, PR, or SD: Intracranial Disease Control Rate (IDCR)

Description

Time Frame

Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months)

Title

Percentage of Participants With BOIR of CR, PR, or SD With Duration of SD for at Least 6 Months: Intracranial Clinical Benefit Rate (ICBR)

Description

Time Frame

Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months)

Title

Overall Survival (OS)

Description

Time Frame

Baseline to the Date of Death from Any Cause (Up to 5 Years)

Title

Percentage of Participants With a Best Response of CR or PR: Extracranial Objective Response Rate (EORR)

Description

Time Frame

Baseline to Disease Progression (Up to 36 Months)

Title

Percentage of Participants With a Best Overall Response of CR, PR, or SD: Extracranial Disease Control Rate (EDCR)

Description

Time Frame

Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months)

Title

Progression Free Survival (PFS) Bi-compartmental

Description

Time Frame

Baseline to Objective Disease Progression or Death from Any Cause (Up to 36 Months)

Title

Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale

Description

Time Frame

Baseline, Cycle 3 (Up to 63 Days)

Title

Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18)

Description

Time Frame

Parts A, B, D, E, F, Cycle 3, Day 1: Predose; Part C, Cycle 4, Day 1: Predose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Call 1-877-CTLILLY (1-877-285-459) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

City of Hope National Medical Center

City

Duarte

State/Province

California

ZIP/Postal Code

91010

Country

United States

Facility Name

University of California - San Diego

City

La Jolla

State/Province

California

ZIP/Postal Code

92037-0845

Country

United States

Facility Name

Univ of California San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94115

Country

United States

Facility Name

John Wayne Cancer Institute

City

Santa Monica

State/Province

California

ZIP/Postal Code

90404

Country

United States

Facility Name

University of Colorado

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

Georgetown University Medical Center

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20007

Country

United States

Facility Name

Florida Cancer Specialists

City

Fort Myers

State/Province

Florida

ZIP/Postal Code

33916-2233

Country

United States

Facility Name

H Lee Moffitt Cancer Center

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612-9497

Country

United States

Facility Name

Kaiser Permanente Center for Health Research

City

Honolulu

State/Province

Hawaii

ZIP/Postal Code

96819

Country

United States

Facility Name

James Graham Brown Cancer Center

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40202

Country

United States

Facility Name

Dana Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Facility Name

University of Michigan

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

Facility Name

Washington University Medical Center

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

Memorial Sloan Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

University of North Carolina at Chapel Hill

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599

Country

United States

Facility Name

Providence Health and Services

City

Portland

State/Province

Oregon

ZIP/Postal Code

97213

Country

United States

Facility Name

SMO Sarah Cannon Research Inst.

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Name

Tennessee Oncology PLLC

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Name

University of Texas MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

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.

City

Nedlands

ZIP/Postal Code

6009

Country

Australia

Facility Name

City

Newcastle

ZIP/Postal Code

2298

Country

Australia

Facility Name

City

Southport

ZIP/Postal Code

4215

Country

Australia

Facility Name

City

Woolloongabba

ZIP/Postal Code

4102

Country

Australia

Facility Name

City

Wien

ZIP/Postal Code

1090

Country

Austria

Facility Name

City

Brussel

ZIP/Postal Code

1000

Country

Belgium

Facility Name

City

Charleroi

ZIP/Postal Code

6000

Country

Belgium

Facility Name

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

City

Liege

ZIP/Postal Code

4000

Country

Belgium

Facility Name

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.

City

Ottawa

ZIP/Postal Code

K1H 8L6

Country

Canada

Facility Name

City

Lille Cedex

ZIP/Postal Code

59020

Country

France

Facility Name

City

Lille

ZIP/Postal Code

59037

Country

France

Facility Name

City

Lyon Cedex 08

ZIP/Postal Code

69373

Country

France

Facility Name

City

Paris Cedex 05

ZIP/Postal Code

75248

Country

France

Facility Name

City

Saint-Brieuc

ZIP/Postal Code

22027

Country

France

Facility Name

City

Toulouse cedex 9

ZIP/Postal Code

31059

Country

France

Facility Name

Hadassah Medical Center - Ein Karem

City

Jerusalem

ZIP/Postal Code

9112001

Country

Israel

Facility Name

Sheba Medical Center

City

Tel Hashomer

ZIP/Postal Code

5265601

Country

Israel

Facility Name

City

Cona

ZIP/Postal Code

44124

Country

Italy

Facility Name

City

Genova

ZIP/Postal Code

16132

Country

Italy

Facility Name

City

Padova

ZIP/Postal Code

35128

Country

Italy

Facility Name

City

Roma

ZIP/Postal Code

00128

Country

Italy

Facility Name

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

City

Madrid

ZIP/Postal Code

28034

Country

Spain

Facility Name

City

Sevilla

ZIP/Postal Code

41013

Country

Spain

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

IPD Sharing Time Frame

Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.

IPD Sharing Access Criteria

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

IPD Sharing URL

https://vivli.org/

Citations:

PubMed Identifier

32694159

Citation

Tolaney SM, Sahebjam S, Le Rhun E, Bachelot T, Kabos P, Awada A, Yardley D, Chan A, Conte P, Dieras V, Lin NU, Bear M, Chapman SC, Yang Z, Chen Y, Anders CK. A Phase II Study of Abemaciclib in Patients with Brain Metastases Secondary to Hormone Receptor-Positive Breast Cancer. Clin Cancer Res. 2020 Oct 15;26(20):5310-5319. doi: 10.1158/1078-0432.CCR-20-1764. Epub 2020 Jul 21. Erratum In: Clin Cancer Res. 2021 Mar 1;27(5):1582.

Results Reference

derived

Links:

URL

https://lillytrialguide.com/en-US/studies/advanced-cancer/JPBO#?postal=

Description

Click here for more information about this study: A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer, Non-small Cell Lung Cancer, or Melanoma that has Spread to the Brain

Learn more about this trial

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

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