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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02308020




Registration number
NCT02308020
Ethics application status
Date submitted
2/12/2014
Date registered
4/12/2014

Titles & IDs
Public title
A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer, Non-small Cell Lung Cancer, or Melanoma That Has Spread to the Brain
Scientific 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
Secondary ID [1] 0 0
I3Y-MC-JPBO
Secondary ID [2] 0 0
15450
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Non-small Cell Lung Cancer 0 0
Melanoma 0 0
Brain Metastases 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Abemaciclib

Experimental: Part A Abemaciclib: HR+, HER2+ Breast Cancer - 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.

Experimental: Part B Abemaciclib: HR+, HER2- Breast Cancer - 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.

Experimental: Part C Abemaciclib: Surgical Resection - 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.

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

Experimental: Part E Abemaciclib: Melanoma - 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.

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


Treatment: Drugs: Abemaciclib
Administered orally

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Intracranial Response Rate (OIRR)
Timepoint [1] 0 0
Baseline to Objective Disease Progression (Up to 36 Months)
Secondary outcome [1] 0 0
Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR)
Timepoint [1] 0 0
Baseline to Earliest Objective Progression or Start of New Anticancer Therapy (Up to 36 Months)
Secondary outcome [2] 0 0
Duration of CR or PR: Duration of Intracranial Response (DOIR)
Timepoint [2] 0 0
Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause (Up to 36 Months)
Secondary outcome [3] 0 0
Percentage of Participants With Best Overall Intracranial Response (BOIR) of CR, PR, or SD: Intracranial Disease Control Rate (IDCR)
Timepoint [3] 0 0
Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months)
Secondary outcome [4] 0 0
Percentage of Participants With BOIR of CR, PR, or SD With Duration of SD for at Least 6 Months: Intracranial Clinical Benefit Rate (ICBR)
Timepoint [4] 0 0
Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months)
Secondary outcome [5] 0 0
Overall Survival (OS)
Timepoint [5] 0 0
Baseline to the Date of Death from Any Cause (Up to 5 Years)
Secondary outcome [6] 0 0
Percentage of Participants With a Best Response of CR or PR: Extracranial Objective Response Rate (EORR)
Timepoint [6] 0 0
Baseline to Disease Progression (Up to 36 Months)
Secondary outcome [7] 0 0
Percentage of Participants With a Best Overall Response of CR, PR, or SD: Extracranial Disease Control Rate (EDCR)
Timepoint [7] 0 0
Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months)
Secondary outcome [8] 0 0
Progression Free Survival (PFS) Bi-compartmental
Timepoint [8] 0 0
Baseline to Objective Disease Progression or Death from Any Cause (Up to 36 Months)
Secondary outcome [9] 0 0
Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale
Timepoint [9] 0 0
Baseline, Cycle 3 (Up to 63 Days)
Secondary outcome [10] 0 0
Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18)
Timepoint [10] 0 0
Parts A, B, D, E, F, Cycle 3, Day 1: Predose; Part C, Cycle 4, Day 1: Predose

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
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
Recruitment hospital [2] 0 0
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
Recruitment hospital [3] 0 0
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
Recruitment hospital [4] 0 0
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
Recruitment postcode(s) [1] 0 0
6009 - Nedlands
Recruitment postcode(s) [2] 0 0
2298 - Newcastle
Recruitment postcode(s) [3] 0 0
4215 - Southport
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Hawaii
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Oregon
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
Austria
State/province [15] 0 0
Wien
Country [16] 0 0
Belgium
State/province [16] 0 0
Brussel
Country [17] 0 0
Belgium
State/province [17] 0 0
Charleroi
Country [18] 0 0
Belgium
State/province [18] 0 0
Leuven
Country [19] 0 0
Belgium
State/province [19] 0 0
Liege
Country [20] 0 0
Canada
State/province [20] 0 0
Ottawa
Country [21] 0 0
France
State/province [21] 0 0
Lille Cedex
Country [22] 0 0
France
State/province [22] 0 0
Lille
Country [23] 0 0
France
State/province [23] 0 0
Lyon Cedex 08
Country [24] 0 0
France
State/province [24] 0 0
Paris Cedex 05
Country [25] 0 0
France
State/province [25] 0 0
Saint-Brieuc
Country [26] 0 0
France
State/province [26] 0 0
Toulouse cedex 9
Country [27] 0 0
Israel
State/province [27] 0 0
Jerusalem
Country [28] 0 0
Israel
State/province [28] 0 0
Tel Hashomer
Country [29] 0 0
Italy
State/province [29] 0 0
Cona
Country [30] 0 0
Italy
State/province [30] 0 0
Genova
Country [31] 0 0
Italy
State/province [31] 0 0
Padova
Country [32] 0 0
Italy
State/province [32] 0 0
Roma
Country [33] 0 0
Spain
State/province [33] 0 0
Barcelona
Country [34] 0 0
Spain
State/province [34] 0 0
Madrid
Country [35] 0 0
Spain
State/province [35] 0 0
Sevilla

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
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)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
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.
Available to whom?
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.