A Phase 1 Study of LY2835219 In Participants With Advance... | NCT01394016

NCT01394016

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
I3Y-MC-JPBA	Other Identifier	Eli Lilly and Company

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Abemaciclib	Experimental	Participants received oral Abemaciclib administered on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as appropriate on Day -3 and then on Days 1 to 27. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. Participants belonging to different Parts received the study drug as specified below: Part A: 50 mg/100 mg/150 mg/225 mg every 24 hours (Q24H) or 75mg/100 mg/150 mg/200 mg/275 mg every 12 hours (Q12H). Parts B, C, D, and E: 150 mg/200 mg Q12H. Part F: 150 mg Q12H. Part G: 200 mg Q12H along with 500 mg Fulvestrant administered intramuscularly.	Drug: Abemaciclib Drug: Fulvestrant

Name	Type	Description	Arm Group Labels	Other Names
Abemaciclib	Drug	Administered orally.	Abemaciclib	LY2835219

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Clinically Significant Effects	The number of participants with clinically significant findings in the study were reported in this outcome measure.	Baseline up to 233 weeks

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR)	ORR is the percentage of participants who exhibit a confirmed complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. DCR is defined as the percentage of participants in the analysis population who exhibit a stable disease (SD) or confirmed CR or PR relative to baseline during the study. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

For all Parts (Dose escalation and expansion): The participant must be, in the judgment of the investigator, an appropriate candidate for experimental therapy either after available standard therapies have ceased to provide clinical benefit (Parts A, B, C, D, E and F) or in combination with fulvestrant (Part G only)
For Dose Escalation (Part A): The participant must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced and/or metastatic
For Dose Expansion (Parts B, C, D, E, F and G): The participant must have histological or cytological evidence of one of the following cancers:
- Part B: Non-small cell lung cancer of any subtype that is advanced and/or metastatic
- Part C: Glioblastoma multiforme that has progressed or recurred after radiotherapy and/or chemotherapy
- Part D: Breast cancer that is advanced and/or metastatic
- Part E: Melanoma that is advanced and/or metastatic
- Part F: Colorectal Cancer
- Part G: Breast Cancer that is not only advanced and/or metastatic but also hormone receptor positive
As defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or the Revised Response Criteria for Malignant Lymphoma
- For Parts A and G: Have measurable or nonmeasurable disease
- For Parts B, C, D, E and F: Have measurable disease
Have given written informed consent prior to any study-specific procedures
Have adequate hematologic, hepatic, and renal function
Have a performance status less than or equal to 1 for Dose Escalation (Part A) and less than or equal to 2 for Dose Confirmation (Parts B, C, D, E, F and G) on the Eastern Cooperative Oncology Group (ECOG) scale
Have discontinued all previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, and investigational therapy) with the exception of fulvestrant (for Part G only) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (treatment related toxicity resolved to baseline) except for residual alopecia
Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug
Females with child bearing potential must have a negative serum pregnancy test within 3 days of the first dose of study drug
Have an estimated life expectancy of greater than or equal to 12 weeks
Are able to swallow capsules

Exclusion Criteria:

Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively
Have a personal history of any of the following conditions: presyncope or syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), sudden cardiac death or sudden cardiac arrest
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)
For Dose Escalation (Part A): Have central nervous system (CNS) malignancy or metastasis
For Dose Confirmation (Parts B, D, E, F and G): Have CNS metastasis that is radiographically or clinically unstable less than 14 days prior to receiving study drug, regardless of whether they are receiving corticosteroids
For Dose Confirmation (Part C): Have glioblastoma multiforme that is radiographically or clinically unstable less than 14 days prior to receiving study drug, regardless of whether they are receiving corticosteroids
Have an acute leukemia
Have received an autologous or allogeneic stem-cell transplant within 75 days of the initial dose of study drug
Females who are pregnant or lactating
Have active bacterial, fungal, and/or known viral infection (for example, human immunodeficiency virus [HIV] antibodies, hepatitis B surface antigen [HBSAg], or hepatitis C antibodies) Screening is not required for enrollment

Contacts/Locations Module

Name	Affiliation	Role
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)	Eli Lilly and Company	Study Director

Locations

Facility	Status	City	State	ZIP	Country	Contacts
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.		Santa Monica	California	90404

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
28540640	Derived	Tate SC, Sykes AK, Kulanthaivel P, Chan EM, Turner PK, Cronier DM. A Population Pharmacokinetic and Pharmacodynamic Analysis of Abemaciclib in a Phase I Clinical Trial in Cancer Patients. Clin Pharmacokinet. 2018 Mar;57(3):335-344. doi: 10.1007/s40262-017-0559-8.
24919854	Derived	Gelbert LM, Cai S, Lin X, Sanchez-Martinez C, Del Prado M, Lallena MJ, Torres R, Ajamie RT, Wishart GN, Flack RS, Neubauer BL, Young J, Chan EM, Iversen P, Cronier D, Kreklau E, de Dios A. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Invest New Drugs. 2014 Oct;32(5):825-37. doi: 10.1007/s10637-014-0120-7. Epub 2014 Jun 13.

IPD Sharing Statement Module

No data available

No data is available for this block.

Completed is defined as for participants from Study Part-A: those who all completed one cycle of treatment or discontinued due to an adverse event and completed study follow up procedures, and for remaining all cohorts (B, C, D, E, F, G) who all were treated until disease progression (objective or symptomatic) or death or discontinued due to an adverse event and completed study follow-up procedures.

Arm/Group Information

ID	Title	Description
FG000	Part A - Cohort 1: 50 Milligrams (mg) Abemaciclib - Every 24 Hours (Q24H)	Participants received 50 mg of oral Abemaciclib administered Q24H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3 and then on Days 1 to 27. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.
FG001	Part A - Cohort 2: 100 mg Abemaciclib - Q24H	Participants received 100 mg of oral Abemaciclib administered Q24H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3 and then on Days 1 to 27. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.
FG002	Part A - Cohort 3: 150 mg Abemaciclib - Q24H	Participants received 150 mg of oral Abemaciclib administered Q24H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3 and then on Days 1 to 27. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.
FG003	Part A - Cohort 4: 225 mg Abemaciclib - Q24H	Participants received 225 mg of oral Abemaciclib administered Q24H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3 and then on Days 1 to 27. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.
FG004	Part A - Cohort 5: 75 mg Abemaciclib - Every 12 Hours (Q12H)	Participants received 75 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.
FG005	Part A - Cohort 6: 100 mg Abemaciclib - Q12H	Participants received 100 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.
FG006	Part A - Cohort 7: 150 mg Abemaciclib - Q12H	Participants received 150 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.
FG007	Part A - Cohort 8: 200 mg Abemaciclib - Q12H	Participants received 200 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.
FG008	Part A - Cohort 9: 275 mg Abemaciclib - Q12H	Participants received 275 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.
FG009	Part B - 150 mg Abemaciclib - Q12H	Participants received 150 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.
FG010	Part B - 200 mg Abemaciclib - Q12H	Participants received 200 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.
FG011	Part C - 150 mg Abemaciclib - Q12H	Participants received 150 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.
FG012	Part C - 200 mg Abemaciclib - Q12H	Participants received 200 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.
FG013	Part D - 150 mg Abemaciclib - Q12H	Participants received 150 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.
FG014	Part D - 200 mg Abemaciclib - Q12H	Participants received 200 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.
FG015	Part E - 150 mg Abemaciclib - Q12H	Participants received 150 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.
FG016	Part E - 200 mg Abemaciclib - Q12H	Participants received 200 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.
FG017	Part F - 150 mg Abemaciclib - Q12H	Participants received 150 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.
FG018	Part G - 200 mg Abemaciclib (Q12H) + Fulvestrant	Participants received 200 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The study drug was given along with 500 mg of fulvestrant administered intramuscularly during the treatment period. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0004 subjects FG0013 subjects FG0023 subjects FG0033 subjects FG0043 subjects FG0054 subjects FG0063 subjects FG0077 subjects FG0083 subjects FG00926 subjects FG01042 subjects FG0112 subjects FG01215 subjects FG01325 subjects FG01422 subjects FG01513 subjects FG01613 subjects FG01715 subjects FG01819 subjects
Received At Least One Dose of Study Drug		FG0004 subjects FG0013 subjects FG0023 subjects FG0033 subjects
COMPLETED		FG0002 subjects FG0013 subjects FG0023 subjects FG0033 subjects FG004
NOT COMPLETED		FG0002 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004

Type	Comment	Reasons
Progressive Disease		FG0002 subjects FG0010 subjects FG0020 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Part A - Cohort 1: 50 mg Abemaciclib - Q24H	Participants received 50 mg of oral Abemaciclib administered Q24H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3 and then on Days 1 to 27. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Clinically Significant Effects

The number of participants with clinically significant findings in the study were reported in this outcome measure.

All participants who received at least one dose of the study drug.

Posted

Count of Participants

Participants

Baseline up to 233 weeks

ID	Title	Description
OG000	Part A - Cohort 1: 50 mg Abemaciclib - Q24H	Participants received 50 mg of oral Abemaciclib administered Q24H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3 and then on Days 1 to 27. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.
OG001	Part A - Cohort 2: 100 mg Abemaciclib - Q24H

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part A - Cohort 1: 50 mg Abemaciclib - Q24H	Participants received 50 mg of oral Abemaciclib administered Q24H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3 and then on Days 1 to 27. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Chief Medical Officer	Eli Lilly and Company	800-545-5979		ClinicalTrials.gov@lilly.com

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 26, 2021	Apr 10, 2023	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Oct 22, 2013	Apr 10, 2023	SAP_001.pdf

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

ID	Term
C000590451	abemaciclib
D000077267	Fulvestrant

ID	Term
D004958	Estradiol
D004963	Estrenes
D004962	Estranes
D013256	Steroids
D000072473

Masking Info

EG0000 events0 affected4 at risk

EG0010 events0 affected3 at risk

EG0020 events0 affected3 at risk

EG0030 events0 affected3 at risk

EG0040 events0 affected3 at risk

EG0050 events0 affected4 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected7 at risk

EG0080 events0 affected3 at risk

EG0090 events0 affected26 at risk

EG0101 events1 affected42 at risk

EG0110 events0 affected2 at risk

EG0120 events0 affected15 at risk

EG0132 events2 affected25 at risk

EG0140 events0 affected22 at risk

EG0150 events0 affected13 at risk

EG0160 events0 affected13 at risk

EG0170 events0 affected15 at risk

EG0181 events1 affected19 at risk

EG0000 events0 affected4 at risk

EG0012 events1 affected3 at risk

EG0021 events1 affected3 at risk

EG0035 events2 affected3 at risk

EG0040 events0 affected3 at risk

EG0052 events1 affected4 at risk

EG0062 events1 affected3 at risk

EG0072 events1 affected7 at risk

EG0082 events2 affected3 at risk

EG00917 events13 affected26 at risk

EG01036 events25 affected42 at risk

EG0110 events0 affected2 at risk

EG0123 events3 affected15 at risk

EG01315 events5 affected25 at risk

EG01416 events11 affected22 at risk

EG01510 events6 affected13 at risk

EG0167 events5 affected13 at risk

EG0176 events6 affected15 at risk

EG01811 events7 affected19 at risk

OG0030(NA to NA)95% CI was not calculable due to insufficient number of participants with events.

OG00432.0(14.9 to 53.5)

OG00518.2(5.2 to 40.3)

OG0060(NA to NA)95% CI was not calculable due to insufficient number of participants with events.

OG0077.7(0.2 to 36.0)

OG0080(NA to NA)95% CI was not calculable due to insufficient number of participants with events.

OG00945.5(16.7 to 76.6)

OG0100(NA to NA)95% CI was not calculable due to insufficient number of participants with events.

Geometric Mean and Geometric Coefficient of Variation couldn't be calculated as only 2 participants had evaluable PK data. Individual values = 3448 ng/mL, 5162 ng/mL.

OG003NA± NAGeometric Mean and Geometric Coefficient of Variation couldn't be calculated as only 2 participants had evaluable PK data. Individual values = 3164 ng/mL, 1576 ng/mL.