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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. (SOLAR-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02437318
Recruitment Status : Active, not recruiting
First Posted : May 7, 2015
Results First Posted : August 13, 2019
Last Update Posted : February 10, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE April 22, 2015
First Posted Date  ICMJE May 7, 2015
Results First Submitted Date  ICMJE June 17, 2019
Results First Posted Date  ICMJE August 13, 2019
Last Update Posted Date February 10, 2020
Actual Study Start Date  ICMJE July 23, 2015
Actual Primary Completion Date June 12, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 22, 2019)
Progression-free Survival (PFS) Per Investigator Assessment in the PIK3CA Mutant Cohort [ Time Frame: Once approximately 243 PFS events in this cohort had been observed, up to 32 months ]
PFS, defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed via a local radiology assessment according to RECIST 1.1
Original Primary Outcome Measures  ICMJE
 (submitted: May 4, 2015)
Progression-free survival (PFS) [ Time Frame: Up to approximatly 36 months ]
PFS, defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed via a local radiology assessment according to RECIST 1.1
Change History Complete list of historical versions of study NCT02437318 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2016)
  • Overall Survival (OS) for Patients With PI3KCA Mutant Status [ Time Frame: Up to approximatly 59 months ]
    OS is defined as the time from date of randomization to date of death due to any cause.
  • Overall Response Rate (ORR) [ Time Frame: Up to approximatly 36 months ]
    ORR is defined as the proportion 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.
  • Time to Definitive Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status [ Time Frame: Baseline, Up to approximatly 36 months ]
    Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
  • Safety and Tolerability of Alpelisib in Combination With Fulvestrant [ Time Frame: Up to approximatly 37 months ]
    Safety will be determined by type, frequency and severity of adverse events per CTCAEv4.03 and type, frequency and severity of laboratory toxicities per CTCAEv4.03. Patients will be followed up for the duration of the study.
  • Time to 10% Deterioration in the Global Health Status/Quality of Life (QOL) Scale Score of the EORTC QLQ-C30 [ Time Frame: Up to approximatly 36 months ]
    Composite measure of change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment will be summarized
  • Plasma Concentration-time Profile of Alpelisib Given in Combinatio With Fulvestrant and Appropriate Pharmacokinetics (PK) Parameters [ Time Frame: Day 8 and Day 15 of Cycle 1, then Day 1 of Cycles 2,4, 6, 8 ]
    Assessment of any potential impact of fulvestrant on the pharmacokinetics of alpelisib by collection of sparse and trough PK samples. PK parameters includes,but not limited to, Cmin, Cmax, t1/2, AUClast for alpelisib (and any relevant metabolites) and fulvestrant
  • PFS Based on Radiology Assessments and Using RECIST 1.1 Criteria [ Time Frame: Baseline, Up to approximatly 36 months ]
    PFS in patients with PIK3CA mutant status and patients with PIK3CA non-mutant status as measured in ctDNA.
  • Clinical Benefit Rate (CBR) [ Time Frame: Up to approximatly 36 months ]
    Clinical benefit rate is defined as the proportion of patients with a best overall response of CR or PR or SD or Non-CR/Non-PD lasting more than 24 weeks based on local investigator assessment.
  • Change in the Global Health Status/(QOL) Scale Score of the EORTC QLQ-C30 [ Time Frame: Baseline, Up to approximatly 36 months ]
    Composite measure of change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment will be summarized
  • Summary Statistics of Fulvestrant and Alpelisib Plasma Concentrations [ Time Frame: Day 8 and Day 15 of Cycle 1, then Day 1 of Cycles 2,4, 6, 8 ]
    Assessment of any potential impact of fulvestrant on the pharmacokinetics of alpelisib by collection of sparse and trough PK samples.
  • PFS for Patients With PIK3CA Non-mutant Status [ Time Frame: Up to approximatly 36 months ]
    PFS based on local radiology assessments and using RECIST 1.1 criteria in the PIK3CA non-mutant cohort
  • OS for Patients With PIK3CA Non-mutant Status [ Time Frame: Up to approximatly 59 months ]
    OS is defined as the time from date of randomization to date of death due to any cause.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 4, 2015)
  • Overall survival (OS) [ Time Frame: Up to approximatly 59 months ]
    OS is defined as the time from date of randomization to date of death due to any cause.
  • Overall Response Rate (ORR) [ Time Frame: Up to approximatly 36 months ]
    ORR is defined as the proportion 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.
  • Time ro definitive deterioration of Eastern Cooperative Oncology Group (ECOG) performance status [ Time Frame: Baseline, Up to approximatly 36 months ]
    Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
  • Safety and Tolerability of Alpelisib in Combination With Fulvestrant [ Time Frame: Up to approximatly 37 months ]
    Safety will be determined by type, frequency and severity of adverse events per CTCAEv4.03 and type, frequency and severity of laboratory toxicities per CTCAEv4.03. Patients will be followed up for the duration of the study.
  • Time to 10% Deterioration in the Global Health Status/Quality of Life (QOL) Scale Score of the EORTC QLQ-C30 [ Time Frame: Up to approximatly 36 months ]
    Composite measure of change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment will be summarized
  • Plasma Concentration-time Profile of Alpelisib Given in Combinatio With Fulvestrant and Appropriate Pharmacokinetics (PK) Parameters [ Time Frame: Day 8 and Day 15 of Cycle 1, then Day 1 of Cycles 2,4, 6, 8 ]
    Assessment of any potential impact of fulvestrant on the pharmacokinetics of alpelisib by collection of sparse and trough PK samples. PK parameters includes,but not limited to, Cmin, Cmax, t1/2, AUClast for alpelisib (and any relevant metabolites) and fulvestrant
  • PFS Based on Radiology Assessments and Using RECIST 1.1 Criteria [ Time Frame: Baseline, Up to approximatly 36 months ]
    PFS in patients with PIK3CA mutant status and patients with PIK3CA non-mutant status as meeasured in ctDNA.
  • Progresion free survival (PFS) [ Time Frame: Up to approximatly 36 months ]
    Supportive analysis for PFS based on Blinded Independent Review Committee (BIRC) and using RECIST 1.1 for the mutant and non-mutant cohorts.
  • Clinical Benefit Rate (CBR) [ Time Frame: Up to approximatly 36 months ]
    Clinical benefit rate is defined as the proportion of patients with a best overall response of CR or PR or SD or Non-CR/Non-PD lasting more than 24 weeks based on local investigator assessment.
  • Change in the Global Health Status/(QOL) Scale Score of the EORTC QLQ-C30 [ Time Frame: Baseline, Up to approximatly 36 months ]
    Composite measure of change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment will be summarized
  • Summary Statistics of Fulvestrant and Alpelisib Plasma Concentrations [ Time Frame: Day 8 and Day 15 of Cycle 1, then Day 1 of Cycles 2,4, 6, 8 ]
    Assessment of any potential impact of fulvestrant on the pharmacokinetics of alpelisib by collection of sparse and trough PK samples.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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.
Official Title  ICMJE A Phase III Randomized Double-blind, Placebo Controlled Study of Alpelisib in Combination With Fulvestrant for Men and Postmenopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment
Brief Summary To determine whether treatment with alpelisib plus fulvestrant prolongs progression-free survival compared to fulvestrant and placebo in men and postmenopausal women with hormone receptor positive (HR+), HER2-negative advanced breast cancer, who received prior treatment with an Aromatase Inhibitor either as (neo)adjuvant or for advanced disease.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Fulvestrant
    Other Name: Faslodex
  • Drug: Alpelisib
  • Drug: Alpelisib placebo
Study Arms  ICMJE
  • Experimental: fulvestrant + alpelisib
    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)
    Interventions:
    • Drug: Fulvestrant
    • Drug: Alpelisib
  • Placebo Comparator: fulvestrant + placebo
    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)
    Interventions:
    • Drug: Fulvestrant
    • Drug: Alpelisib placebo
Publications * André 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, Pápai 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 1, 2018)
572
Original Estimated Enrollment  ICMJE
 (submitted: May 4, 2015)
820
Estimated Study Completion Date  ICMJE May 27, 2020
Actual Primary Completion Date June 12, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • If female, patient is postmenopausal
  • Patient has identified PIK3CA status
  • Patients may 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 advanced breast cancer, then relapsed with documented evidence of progression while on or after only one line of endocrine therapy
  • Patient has recurrence or progression of disease during or after AI therapy (i.e.

letrozole, anastrozole, exemestane).

  • Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive breast cancer by local laboratory and has HER2 negative breast cancer
  • Patient has either measurable disease per RECIST 1.1 criteria OR at least one predominantly lytic bone lesion must be present
  • Patient has adequate bone marrow function

Exclusion Criteria:

  • Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment
  • Patient has received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR or AKT inhibitor (pre-treatment with CDK4/6 inhibitors is allowed)
  • Patient with inflammatory breast cancer at screening
  • Patients with Child pugh score B or C
  • Patients with an established diagnosis of diabetes mellitus type I or not controlled type II
  • Patient has Eastern Cooperative Oncology Group (ECOG) performance status 2 or more
  • Patient with CNS involvement unless he/she is at least 4 weeks from prior therapy completion to starting the study treatment and has stable CNS tumor at time of screening and not receiving steroids and/or enzyme inducing ant-epileptic medications for brain metastases
  • Patient has participated in a prior investigational study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer
  • Patient has a history of acute pancreatitis within 1 year of screening or a past medical history of chronic pancreatitis
  • Patient who relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for metastatic disease

Other protocol-defined inclusion/esclusion criteria may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   Chile,   Czechia,   Denmark,   France,   Germany,   Greece,   Hong Kong,   Hungary,   India,   Israel,   Italy,   Japan,   Korea, Republic of,   Lebanon,   Mexico,   Netherlands,   Peru,   Portugal,   Romania,   Russian Federation,   Spain,   Sweden,   Taiwan,   Thailand,   United Arab Emirates,   United Kingdom,   United States
Removed Location Countries Czech Republic,   Turkey
 
Administrative Information
NCT Number  ICMJE NCT02437318
Other Study ID Numbers  ICMJE CBYL719C2301
2015-000340-42 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP