TriangleNCT02437318 · CITED IN SOURCE DOCUMENTS
Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant in Men and Postmenopausal Women With Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment.
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2025-02-13
To determine whether treatment with alpelisib plus fulvestrant prolonged progression-free survival (PFS) compared to fulvestrant and placebo in men and postmenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor-2 (HER2)-negative advanced breast cancer, who received prior treatment with an aromatase Inhibitor (AI) either as (neo)adjuvant or for advanced disease.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Progression-free Survival (PFS) Per Investigator Assessment in the PIK3CA Mutant Cohort
Overall Survival (OS) in the PIK3CA Mutant Cohort
PFS Per Investigator Assessment in the PIK3CA Non-mutant Cohort
OS in the PIK3CA Non-mutant Cohort
Overall Response Rate (ORR) Per Investigator Assessment
Clinical Benefit Rate (CBR) Per Investigator Assessment
Time to Definitive Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score From Baseline
Time to 10% Deterioration in the Global Health Status (GHS) /Quality of Life (QOL) Scale Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)
Change From Baseline in the GHS/QOL Scale Score of the EORTC QLQ-C30
Trough Plasma Concentration of Alpelisib
Trough Plasma Concentration of Fulvestrant
PFS Per Investigator Criteria in Subjects With PIK3CA Mutation Status Measured in ctDNA at Baseline
All Collected Deaths
Updated PFS Per Investigator Assessment in the PIK3CA Mutant Cohort (Longer Follow-up)
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: * If female, the patient was postmenopausal. * The patient had identified PIK3CA status. * Patients could be: * Relapsed with documented evidence of progression while on (neo)adjuvant endocrine therapy or within 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for metastatic disease. * Relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine therapy and then subsequently progressed with documented evidence of progression while on or after only one line of endocrine therapy for metastatic disease. * Newly diagnosed with advanced breast cancer, then relapsed with documented evidence of progression while on or after only one line of endocrine therapy. * The patient had recurrence or progression of the disease during or after AI therapy (i.e., letrozole, anastrozole, exemestane). * The patient had a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive breast cancer by a local laboratory and had HER2 negative breast cancer. * The patient had either measurable disease per RECIST 1.1 criteria or at least one predominantly lytic bone lesion present. * The patient had adequate bone marrow function. Exclusion Criteria: * The patient had symptomatic visceral disease or any disease burden that made the patient ineligible for endocrine therapy per the investigator's best judgment. * The patient had received prior treatment with chemotherapy (except for neoadjuvant/adjuvant chemotherapy), fulvestrant, any PI3K, mTOR, or AKT inhibitor (pre-treatment with CDK4/6 inhibitors was allowed). * The patient had inflammatory breast cancer at screening. * Patients had Child pugh score B or C. * Patients had an established diagnosis of diabetes mellitus type I or uncontrolled type II. * The patient had Eastern Cooperative Oncology Group (ECOG) performance status 2 or more. * The patient had CNS involvement unless he/she was at least 4 weeks from prior therapy completion to starting the study treatment and had a stable CNS tumor at the time of screening and was not receiving steroids and/or enzyme-inducing antiepileptic medications for brain metastases. * The patient had participated in a prior investigational study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever was longer. * The patient had a history of acute pancreatitis within 1 year of screening or a past medical history of chronic pancreatitis. * The patient relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for metastatic disease.
- healthy Volunteers
- false
- maximum Age
- 100 Years
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Subjects treated with alpelisib (300 mg; oral; once daily) in combination with fulvestrant (500 mg; intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle)
- intervention Names
- Drug: Fulvestrant
- Drug: Alpelisib
- label
- Fulvestrant + alpelisib
- type
- EXPERIMENTAL
- description
- Subjects were treated with placebo (300 mg; oral; once daily) in combination with fulvestrant (500 mg; intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle)
- intervention Names
- Drug: Fulvestrant
- Drug: Placebo
- label
- Fulvestrant + placebo
- type
- PLACEBO_COMPARATOR
- interventions
- arm Group Labels
- Fulvestrant + alpelisib
- Fulvestrant + placebo
- description
- 500 mg of fulvestrant administered via intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle
- name
- Fulvestrant
- type
- DRUG
- arm Group Labels
- Fulvestrant + alpelisib
- description
- 300 mg of alpelisib tablets for oral use administered once daily
- name
- Alpelisib
- other Names
- BYL719
- type
- DRUG
- arm Group Labels
- Fulvestrant + placebo
- description
- 300 mg of placebo tablets for oral use administered once daily
- name
- Placebo
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- TRIPLE
- who Masked
- PARTICIPANT
- CARE_PROVIDER
- INVESTIGATOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 572
- type
- ACTUAL
Registered outcome plans (not posted results)
- other Outcomes
- description
- PFS was defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS was assessed via a local radiology assessment according to RECIST 1.1. If a patient did not have an event, PFS was censored at the date of last adequate tumor assessment. The PFS distribution was estimated using Kaplan-Meier methodology. This analysis was conducted at the time of the final OS analysis (when approximately 178 deaths in the PIK3CA mutant cohort had been achieved) and includes a longer follow-up time. Progression was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
- measure
- Updated PFS Per Investigator Assessment in the PIK3CA Mutant Cohort (Longer Follow-up)
- time Frame
- Up to 55.7 months
- primary Outcomes
- description
- PFS was defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS was assessed via a local radiology assessment according to RECIST 1.1. If a patient did not have an event, PFS was censored at the date of last adequate tumor assessment. The PFS distribution was estimated using Kaplan-Meier methodology. Progression was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
- measure
- Progression-free Survival (PFS) Per Investigator Assessment in the PIK3CA Mutant Cohort
- time Frame
- Once approximately 243 PFS events in the PIK3CA mutant cohort had been observed, up to 33.3 months
- secondary Outcomes
- description
- OS was defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last known date patient alive. The OS distribution was estimated using Kaplan-Meier methodology.
- measure
- Overall Survival (OS) in the PIK3CA Mutant Cohort
- time Frame
- Once approximately 178 deaths in the PIK3CA mutant cohort had been observed, up to 55.7 months
- description
- PFS was defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS was assessed via a local radiology assessment according to RECIST 1.1. If a patient did not have an event, PFS was censored at the date of last adequate tumor assessment. The PFS distribution was estimated using Kaplan-Meier methodology. Progression was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
- measure
- PFS Per Investigator Assessment in the PIK3CA Non-mutant Cohort
- time Frame
- Up to 56.4 months
- description
- OS was defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last known date patient alive. The OS distribution was estimated using Kaplan-Meier methodology.
- measure
- OS in the PIK3CA Non-mutant Cohort
- time Frame
- Up to 56.4 months
- description
- ORR was defined as the percentage of patients with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
- measure
- Overall Response Rate (ORR) Per Investigator Assessment
- time Frame
- Up to 56.4 months
- description
- Clinical benefit rate was defined as the percentage of patients with a best overall response of CR or PR or stable disease (SD) or Non-CR/Non-PD lasting more than 24 weeks based on local investigator assessment according to RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
- measure
- Clinical Benefit Rate (CBR) Per Investigator Assessment
- time Frame
- Up to 56.4 months
- description
- ECOG PS categorized patients based on their ability to perform daily activities and self-care, with scores ranging from 0 to 5. A score of 0 indicated no restrictions in activity, while higher scores indicated increasing limitations. Time to definitive deterioration of ECOG PS by one score was defined as the time from the date of randomization to the date of the event, defined as experiencing at least one score lower than the baseline. A deterioration was considered definitive if no improvements in the ECOG PS were observed at a subsequent time. The Kaplan-Meier method was used to estimate the distribution. Patients receiving any further therapy prior to definitive worsening were censored at their date of last assessment prior to start of therapy. Patients that had not worsened at the data cutoff point were censored at the date of last assessment.
- measure
- Time to Definitive Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score From Baseline
- time Frame
- From baseline up to 56.4 months
- description
- The EORTC QLQ-C30 is a questionnaire that includes 5 functional scales, 3 symptom scales, 1 GHS/QoL scale, and 6 single items. GHS/QoL scale score ranges between 0 and 100. A high score for GHS/QoL represents better functioning or QoL.The time to definitive 10% deterioration was defined as the time from the date of randomization to the date of event, which was defined as at least 10% relative to baseline worsening of the GHS/QoL score (without further improvement above the threshold) or death due to any cause. The Kaplan-Meier method was used to estimate the distribution. If a patient had not had an event, time to deterioration was censored at the date of the last adequate QoL evaluation.
- measure
- Time to 10% Deterioration in the Global Health Status (GHS) /Quality of Life (QOL) Scale Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)
- time Frame
- From baseline up to 55.7 months
- description
- The EORTC QLQ-C30 is a questionnaire that includes 5 functional scales, 3 symptom scales, 1 GHS/QoL scale, and 6 single items. GHS/QoL scale score ranges between 0 and 100. A high score for GHS/QoL represents better functioning or QoL.The change from baseline in the GHS/QoL score was assessed. A positive change from baseline indicated improvement. For each cohort, this analysis only included assessments up to the time point where there were at least 10 patients on each of the 2 treatment groups.
- measure
- Change From Baseline in the GHS/QOL Scale Score of the EORTC QLQ-C30
- time Frame
- Baseline, every 8 weeks after randomization during the first 18 months and thereafter every 12 weeks, up to 120 weeks.
- description
- Pre-dose plasma concentrations of alpelisib were assessed. Only participants randomized to the alpelisib + fulvestrant arm were included in this analysis.
- measure
- Trough Plasma Concentration of Alpelisib
- time Frame
- Day 8 and Day 15 of Cycle 1, then Day 1 of Cycles 2, 4, 6 and 8. Cycle = 28 days
- description
- Pre-dose plasma concentrations of fulvestrant were assessed.
- measure
- Trough Plasma Concentration of Fulvestrant
- time Frame
- Day 15 of Cycle 1, then Day 1 of Cycles 2, 4, 6 and 8. Cycle = 28 days
- description
- PFS was defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS was assessed via a local radiology assessment according to RECIST 1.1. If a patient did not have an event, PFS was censored at the date of last adequate tumor assessment. The PFS distribution was estimated using Kaplan-Meier methodology. Subjects were analyzed according to the PIK3CA mutation status (mutant or non-mutant) as identified using plasma ctDNA. Progression was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
- measure
- PFS Per Investigator Criteria in Subjects With PIK3CA Mutation Status Measured in ctDNA at Baseline
- time Frame
- From baseline up to 56.4 months
Full study description
- brief Summary
- To determine whether treatment with alpelisib plus fulvestrant prolonged progression-free survival (PFS) compared to fulvestrant and placebo in men and postmenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor-2 (HER2)-negative advanced breast cancer, who received prior treatment with an aromatase Inhibitor (AI) either as (neo)adjuvant or for advanced disease.
- detailed Description
- This was a randomized, double-blind, placebo-controlled, international multicenter Phase III study that evaluated the efficacy and safety of treatment with alpelisib plus fulvestrant versus placebo plus fulvestrant in men and postmenopausal women with HR-positive, HER2-negative advanced breast cancer which had progressed on or after AI treatment. Subjects were allocated to either the PIK3CA mutant or PIK3CA non-mutant cohort, based on central testing of hotspot-mutations in tumor tissue. Subjects with unknown results were not eligible. Within each cohort, subjects were randomized in a 1:1 ratio to receive either alpelisib 300 mg orally once daily (q.d.), in combination with fulvestrant 500 mg intramuscular (i.m.) on Days 1 and 15 of Cycle 1 and Day 1 of a 28-day cycle thereafter, or placebo daily in combination with fulvestrant 500 mg following the same treatment regimen. Subjects were treated until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason. All subjects who discontinued study treatment were followed for safety, until 30 days after last study treatment administration, except in the case of death, loss to follow-up, or withdrawal of consent. Subjects who discontinued study treatment for reasons other than disease progression or withdrawal of consent, were followed until disease progression, death, withdrawal of consent, loss to follow-up, or subject/guardian decision (post-treatment efficacy follow-up). Finally, all subjects were followed for survival after discontinuation of study treatment and tumor evaluations until the subject's death, loss to follow-up, or withdrawal of consent for survival follow-up (post-treatment survival follow-up)
Source references
- references
- citation
- Borrego MR, Lu YS, Reyes-Cosmelli F, Park YH, Yamashita T, Chiu J, Airoldi M, Turner N, Fein L, Ghaznawi F, Singh J, Pantoja K, Schnell C, Akdere M, Chia S. SGLT2 inhibition improves PI3Kalpha inhibitor-induced hyperglycemia: findings from preclinical animal models and from patients in the BYLieve and SOLAR-1 trials. Breast Cancer Res Treat. 2024 Nov;208(1):111-121. doi: 10.1007/s10549-024-07405-8. Epub 2024 Aug 23.
- pmid
- 39177931
- type
- DERIVED
- citation
- Rodon J, Demanse D, Rugo HS, Burris HA, Simo R, Farooki A, Wellons MF, Andre F, Hu H, Vuina D, Quadt C, Juric D. A risk analysis of alpelisib-induced hyperglycemia in patients with advanced solid tumors and breast cancer. Breast Cancer Res. 2024 Mar 4;26(1):36. doi: 10.1186/s13058-024-01773-1.
- pmid
- 38439079
- type
- DERIVED
- citation
- Ciruelos EM, Rugo HS, Mayer IA, Levy C, Forget F, Delgado Mingorance JI, Safra T, Masuda N, Park YH, Juric D, Conte P, Campone M, Loibl S, Iwata H, Zhou X, Park J, Ridolfi A, Lorenzo I, Andre F. Patient-Reported Outcomes in Patients With PIK3CA-Mutated Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer From SOLAR-1. J Clin Oncol. 2021 Jun 20;39(18):2005-2015. doi: 10.1200/JCO.20.01139. Epub 2021 Mar 29.
- pmid
- 33780274
- type
- DERIVED
- citation
- Andre F, Ciruelos EM, Juric D, Loibl S, Campone M, Mayer IA, Rubovszky G, Yamashita T, Kaufman B, Lu YS, Inoue K, Papai Z, Takahashi M, Ghaznawi F, Mills D, Kaper M, Miller M, Conte PF, Iwata H, Rugo HS. Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1. Ann Oncol. 2021 Feb;32(2):208-217. doi: 10.1016/j.annonc.2020.11.011. Epub 2020 Nov 25.
- pmid
- 33246021
- type
- DERIVED
- citation
- Rugo HS, Andre F, Yamashita T, Cerda H, Toledano I, Stemmer SM, Jurado JC, Juric D, Mayer I, Ciruelos EM, Iwata H, Conte P, Campone M, Wilke C, Mills D, Lteif A, Miller M, Gaudenzi F, Loibl S. Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer. Ann Oncol. 2020 Aug;31(8):1001-1010. doi: 10.1016/j.annonc.2020.05.001. Epub 2020 May 13.
- pmid
- 32416251
- type
- DERIVED
- citation
- Andre F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, Iwata H, Conte P, Mayer IA, Kaufman B, Yamashita T, Lu YS, Inoue K, Takahashi M, Papai Z, Longin AS, Mills D, Wilke C, Hirawat S, Juric D; SOLAR-1 Study Group. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019 May 16;380(20):1929-1940. doi: 10.1056/NEJMoa1813904.
- pmid
- 31091374
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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