A Study of Abemaciclib (LY2835219) Combined With Fulvestrant in Women With Hormone Receptor Positive HER2 Negative Breast Cancer
- Conditions
- Breast Neoplasms
- Interventions
- Registration Number
- NCT02107703
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The main purpose of this study is to compare progression-free survival for women with hormone receptor positive (HR+), human epidermal growth factor receptor (HER2) negative advanced breast cancer receiving either abemaciclib + fulvestrant or fulvestrant alone. Participants will be randomized to abemaciclib or placebo in a 2:1 ratio. The study will last about 9 months for each participant.
For the endocrine naïve cohort, all participants will received abemaciclib + fulvestrant.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 669
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Abemaciclib + Fulvestrant Fulvestrant Abemaciclib 150 milligram (mg) administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met. Placebo + Fulvestrant Placebo Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met. Abemaciclib + Fulvestrant Abemaciclib Abemaciclib 150 milligram (mg) administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met. Placebo + Fulvestrant Fulvestrant Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) From Date of Randomization until Disease Progression or Death Due to Any Cause (Up To 31 Months) PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (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 randomization, 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.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 31 Months) 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. 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.
Percentage of Participants Achieving CR, PR or Stable Disease (SD) (Disease Control Rate [DCR]) From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months) 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. 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.
Percentage of Participants With CR, PR or SD With a Duration of At Least 6 Months (Clinical Benefit Rate [CBR]) From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months) Clinical benefit rate defined as percentage of participants with best overall response of CR, PR, or SD with a duration of at least 6 months.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.PD was at least a 20% increase in 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.
Change From Baseline in Pain and Symptom Burden Assessment Using the Modified Brief Pain Inventory-Short Form (mBPI-sf) Baseline, End of Study (Up To 31 Months) 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). The overall change is based on the estimated main treatment effect. Least square (LS) Mean value was controlled for Treatment, visit, Treatment\*Visit and baseline.
Overall Survival (OS) From Date of Randomization until Death Due to Any Cause (Up To 72 Months) OS defined as the time from the date of randomization 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. The final analysis of the OS outcome was conducted after 440 OS events had been observed.
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months) 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. 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.
Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of Abemaciclib, Its Metabolites M2 and M20 Cycle 1 Day 1 2-4 hours (h) post dose, Cycle 1 Day 15 4 and 7h post dose, Cycle 2 Day 1 pre dose and 3h post dose, Cycle 3 Day1 pre dose Area Under the Plasma Concentration versus Time Curve from Time Zero to Infinity (AUC\[0-∞\]) was evaluated for Abemaciclib and Metabolites M2 and M20.
Change From Baseline to Short Term Follow up in Quality of Life Using the EORTC QLQ-BR23 (Breast) Questionnaire Baseline, Short Term Follow Up (Up To 31 Months) EORTC-QLQ-BR23 measured multi-item functional scales for body image, sexual functioning and future perspective and measured single item symptoms scales which assessed systemic therapy side effects, breast symptoms and arm symptoms. For functional scales, scores ranged from 0 to 100 where higher scores represented a better level of functioning. For symptoms scales, scores ranged from 0 to 100 where higher scores represented a greater degree of symptoms. LS Mean value of changing from baseline to short follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment\*Visit and baseline.
Change From Baseline in Health Status Using the EuroQol 5-Dimension 5 Level (EQ-5D 5L) Baseline, End of Study (Up To 31 Months) European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. The EQ-5D-5L is assessed using a visual analog scale (VAS) that ranged from 0 to 100mm, where 0 is the worst health you can imagine and 100 is the best health you can imagine. A higher score indicates better health state. LS Mean value was controlled for Treatment, visit, Treatment\*Visit and baseline.
Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Baseline, Short Term Follow Up (Up To 31 Months) 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, scores range from 0 to 110 with higher scores representing a better level of functioning. For symptoms scales, scores range from 0 to 100 with higher scores representing a greater degree of symptoms. LS Mean value of changing from baseline to short follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment\*Visit and baseline.
Trial Locations
- Locations (139)
St. Bernards Medical Center
🇺🇸Jonesboro, Arkansas, United States
Highlands Oncology Group
🇺🇸Springdale, Arkansas, United States
University of California - San Diego
🇺🇸La Jolla, California, United States
Kaiser Permanente
🇺🇸Riverside, California, United States
Univ of California San Francisco
🇺🇸San Francisco, California, United States
Stanford University Clinic
🇺🇸Stanford, California, United States
Palm Beach Cancer Institue
🇺🇸West Palm Beach, Florida, United States
Holy Cross Hospital
🇺🇸Fort Lauderdale, Florida, United States
Florida Cancer Specialists - South
🇺🇸Fort Myers, Florida, United States
Florida Cancer Specialists - North
🇺🇸Saint Petersburg, Florida, United States
Scroll for more (129 remaining)St. Bernards Medical Center🇺🇸Jonesboro, Arkansas, United States