A Study of Abemaciclib (LY2835219) In Participants With Previously Treated Breast Cancer That Has Spread

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate whether the study drug known as abemaciclib is effective in treating participants with breast cancer who have already tried other drug treatments.

Official Title
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A Phase 2 Study of LY2835219 for Patients With Previously Treated Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Abemaciclib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria. Have a diagnosis of Hormone Receptor Positive (HR+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) breast cancer. Recurrent, locally advanced, unresectable or metastatic breast cancer with disease progression following anti-estrogen therapy. Prior treatment with at least 2 chemotherapy regimens: At least 1 of these regimens must have been administered in the metastatic setting. At least 1 of these regimens must have contained a taxane. No more than 2 prior chemotherapy regimens in the metastatic setting. Have a performance status (PS) of 0 to 1 on the Eastern Cooperative Oncology Group scale. Have discontinued all previous therapies for cancer. Have the presence of measureable disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.1. Exclusion Criteria: Have either a history of central nervous system (CNS) metastasis or evidence of CNS metastasis on the magnetic resonance image of brain obtained at baseline. Received prior therapy with another cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor. 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. Have had major surgery within 14 days of the initial dose of study drug. Have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abemaciclib<br>200 milligrams (mg) abemaciclib given orally once every 12 hours for 28 days (1 cycle). Participants may continue to receive treatment until discontinuation criteria are met. | Drug: Abemaciclib<br>* Administered orally<br>* Other names: LY2835219;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) | ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. | From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 14 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS defined as the time from first dose date to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive. | From Date of First Dose until Death Due to Any Cause (Up To 27 Months) | 
| Duration of Response (DOR) | DOR was the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR were defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date. | From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 14 Months) | 
| Progression Free Survival (PFS) | PFS defined as the time from the first day of therapy to the first evidence of disease progression as defined by RECIST v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date. | From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 27 Months) | 
| Percentage of Participants With CR, PR or SD (Disease Control Rate [DCR]) | Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. | From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 14 Months) | 
| Percentage of Participants With Tumor Response of Stable Disease (SD) for at Least 6 Months, Partial Response (PR) or Complete Response (CR) (Clinical Benefit Rate) | Clinical benefit rate defined as percentage of patients with best overall response of CR, PR, or SD with a duration of at least 6 months. CR, PR, or SD were defined using RECIST, v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. Percentage of participants = (participants with CR+PR+SD with a duration of at least 6 months /number of participants enrolled) *100. | From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 14 Months) | 
| Number of Participants With Categorical Change From Baseline in Brief Pain Inventory Short Form (mBPI-sf) - Worst Pain Score | A self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). | Cycle 6 Day 1 | 
| Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) for Abemaciclib and Metabolites M2 and M20 | Area Under the Concentration versus Time Curve from Time Zero to Infinity (AUC[0-∞]) was evaluated for Abemaciclib and Metabolites M2 and M20 | Cycle 1 Day 1 pre dose, Cycle 1 Day 15 4 hours (h) and 7 h post dose, Cycle 2 Day 1 pre dose and 3 h post dose, Cycle 3 Day1 pre dose | 
| Number of Participants With Categorical Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Global Health Status Score | EORTC QLQ-C30 v3.0 was a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, cognitive, emotional, and social), global health status, and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms. | Cycle 6 Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endocrine Therapy, Taxane, MONARCH 1