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.

Breast Cancer Clinical Trial

— SOLAR-1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02437318
• Other study ID #: CBYL719C2301
• Secondary ID: 2015-000340-42
• Status: Completed
• Phase: Phase 3
• Start date: July 23, 2015
• Est. completion date: June 9, 2023

Study information

• Verified date: November 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 572
• Est. completion date: June 9, 2023
• Est. primary completion date: June 12, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Fulvestrant

• Alpelisib

• Alpelisib placebo

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Berazategui	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	La Rioja
Argentina	Novartis Investigative Site	Rio Negro	Viedma
Australia	Novartis Investigative Site	Elizabeth Vale	South Australia
Australia	Novartis Investigative Site	Melbourne	Victoria
Australia	Novartis Investigative Site	Wahroonga	New South Wales
Australia	Novartis Investigative Site	Wooloongabba	Queensland
Austria	Novartis Investigative Site	Linz
Austria	Novartis Investigative Site	Vienna
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Edegem	Antwerpen
Belgium	Novartis Investigative Site	Jette	Brussel
Belgium	Novartis Investigative Site	Libramont
Belgium	Novartis Investigative Site	Ottignies
Belgium	Novartis Investigative Site	Sint Niklaas	Oost Vlaanderen
Belgium	Novartis Investigative Site	Verviers
Brazil	Novartis Investigative Site	Lajeado	RS
Brazil	Novartis Investigative Site	Natal	RN
Brazil	Novartis Investigative Site	Sao Jose do Rio Preto
Brazil	Novartis Investigative Site	Sao Paulo
Brazil	Novartis Investigative Site	Sao Paulo	SP
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Varna
Bulgaria	Novartis Investigative Site	Varna
Canada	Novartis Investigative Site	Calgary	Alberta
Canada	Novartis Investigative Site	Cambridge	Ontario
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Temuco	Araucania
Chile	Novartis Investigative Site	Vina del Mar
Czechia	Novartis Investigative Site	Hradec Kralove	Czech Republic
Czechia	Novartis Investigative Site	Prague 8
Czechia	Novartis Investigative Site	Praha 4	Czech Republic
Czechia	Novartis Investigative Site	Zlin	Czech Republic
France	Novartis Investigative Site	Angers 02
France	Novartis Investigative Site	Avignon
France	Novartis Investigative Site	Caen
France	Novartis Investigative Site	Clermont Ferrand
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	La Roche sur Yon cedex 9
France	Novartis Investigative Site	Le Chesnay
France	Novartis Investigative Site	Levallois-Perret
France	Novartis Investigative Site	Lyon Cedex 08
France	Novartis Investigative Site	Marseille cedex 20	Bouches Du Rhone
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Nimes
France	Novartis Investigative Site	Rouen
France	Novartis Investigative Site	Saint-Herblain Cédex
France	Novartis Investigative Site	Toulouse
France	Novartis Investigative Site	Villejuif Cedex
Germany	Novartis Investigative Site	Aschaffenburg
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Friedrichshafen
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Homburg
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Leipzig	Sachsen
Germany	Novartis Investigative Site	Luebeck	Schleswig-Holstein
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Potsdam
Germany	Novartis Investigative Site	Recklinghausen	North Rhine-westphalia
Germany	Novartis Investigative Site	Rostock
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Velbert
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Thessaloniki	GR
Hong Kong	Novartis Investigative Site	Hong Kong
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Nyiregyhaza
Hungary	Novartis Investigative Site	Szekszard
India	Novartis Investigative Site	Mumbai
India	Novartis Investigative Site	Nagpur - Maharashtra	Maharashtra
India	Novartis Investigative Site	Vijayawada	Andhra Pradesh
Israel	Novartis Investigative Site	Beer-Sheva
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Petach Tikva
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Ancona	AN
Italy	Novartis Investigative Site	Aviano	PN
Italy	Novartis Investigative Site	Chieti	CH
Italy	Novartis Investigative Site	Meldola	FC
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Negrar	VR
Italy	Novartis Investigative Site	Padova	PD
Italy	Novartis Investigative Site	Palermo	PA
Italy	Novartis Investigative Site	Pontedera	PI
Italy	Novartis Investigative Site	Rionero in Vulture	PZ
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Sassari	SS
Italy	Novartis Investigative Site	Savona	SV
Italy	Novartis Investigative Site	Torino	TO
Japan	Novartis Investigative Site	Akashi	Hyogo
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Japan	Novartis Investigative Site	Isehara	Kanagawa
Japan	Novartis Investigative Site	Kagoshima-city	Kagoshima
Japan	Novartis Investigative Site	Kitaadachi-gun	Saitama
Japan	Novartis Investigative Site	Kumamoto City	Kumamoto
Japan	Novartis Investigative Site	Maebashi city	Gunma
Japan	Novartis Investigative Site	Matsuyama	Ehime
Japan	Novartis Investigative Site	Minato ku	Tokyo
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Sapporo-city	Hokkaido
Japan	Novartis Investigative Site	Yokohama-city	Kanagawa
Korea, Republic of	Novartis Investigative Site	Bundang Gu	Gyeonggi Do
Korea, Republic of	Novartis Investigative Site	Gyeonggi do	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Lebanon	Novartis Investigative Site	Ashrafieh
Lebanon	Novartis Investigative Site	Beirut
Lebanon	Novartis Investigative Site	Saida
Mexico	Novartis Investigative Site	Monterrey NL	Monterrey
Mexico	Novartis Investigative Site	San Luis Potosi
Netherlands	Novartis Investigative Site	Terneuzen
Netherlands	Novartis Investigative Site	Venray	CE
Peru	Novartis Investigative Site	Lima
Peru	Novartis Investigative Site	San Borja	Lima
Peru	Novartis Investigative Site	Surquillo	Lima
Romania	Novartis Investigative Site	Craiova	Dolj
Romania	Novartis Investigative Site	Floresti	Cluj
Romania	Novartis Investigative Site	Iasi
Russian Federation	Novartis Investigative Site	Arkhangelsk
Russian Federation	Novartis Investigative Site	Ryazan
Russian Federation	Novartis Investigative Site	St Petersburg
Spain	Novartis Investigative Site	Alicante	Comunidad Valenciana
Spain	Novartis Investigative Site	Badajoz	Extremadura
Spain	Novartis Investigative Site	Badalona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Cataluna
Spain	Novartis Investigative Site	Caceres	Extremadura
Spain	Novartis Investigative Site	Castellon	Comunidad Valenciana
Spain	Novartis Investigative Site	El Palmar	Murcia
Spain	Novartis Investigative Site	Jerez	Cadiz
Spain	Novartis Investigative Site	La Laguna	Santa Cruz De Tenerife
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Palma De Mallorca	Islas Baleares
Spain	Novartis Investigative Site	Pozuelo de Alarcon	Madrid
Spain	Novartis Investigative Site	Santiago de Compostela	Galicia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Sweden	Novartis Investigative Site	Gavle
Sweden	Novartis Investigative Site	Oerebro
Sweden	Novartis Investigative Site	Vasteras
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Thailand	Novartis Investigative Site	Bangkok	THA
Thailand	Novartis Investigative Site	Bangkok
United Kingdom	Novartis Investigative Site	Leicester
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Plymouth	Devon
United States	Mercy Medical Center SC-2	Baltimore	Maryland
United States	Beverly Hills Cancer Center	Beverly Hills	California
United States	St Vincent Frontier Cancer Center	Billings	Montana
United States	Massachusetts General Hospital Updated Regulatory	Boston	Massachusetts
United States	Lahey Clinic	Burlington	Massachusetts
United States	Ironwood Cancer and Research Centers Chandler 2	Chandler	Arizona
United States	Rush University Medical Center Rush Uni Medical Center	Chicago	Illinois
United States	University Hospitals of Cleveland Seidman Cancer Center SC	Cleveland	Ohio
United States	Good Samaritan Regional Medical Center Good Samaritan Reg Med Ctr	Corvallis	Oregon
United States	Texas Oncology PA Dallas Presbyterian Hospital SC-1	Dallas	Texas
United States	City of Hope National Medical Center	Duarte	California
United States	El Paso, Texas Oncology	El Paso	Texas
United States	NorthShore University Health System NorthShore University	Evanston	Illinois
United States	Virginia Cancer Specialists SC	Fairfax	Virginia
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	Florida Cancer Specialists FL Cancer Specialists	Fort Myers	Florida
United States	Fort Wayne Medical Oncology/Hematology, Inc. Dept.of Fort Wayne Med Onc/Hem	Fort Wayne	Indiana
United States	Prisma Health Upstate SC-2	Greenville	South Carolina
United States	St. Luke's Cancer Institute SC	Kansas City	Missouri
United States	Scripps Clinic SC	La Jolla	California
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	Edward Cancer Center SC	Naperville	Illinois
United States	Tennessee Oncology SC-3	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey SC-2	New Brunswick	New Jersey
United States	Detroit Clinical Research Center	Owosso	Michigan
United States	Florida Cancer Specialists-North SC	Saint Petersburg	Florida
United States	Mays Cancer Ctr Uthsa Mdacc InstituteForDrugDevelopment(4)	San Antonio	Texas
United States	Kaiser Permanente - California Southern	San Diego	California
United States	University of California San Francisco	San Francisco	California
United States	Mayo Clinic - Arizona	Scottsdale	Arizona
United States	Avera Cancer SC	Sioux Falls	South Dakota
United States	St. Francis Health Comprehensive Cancer Center SC	Topeka	Kansas
United States	Texas Oncology Northeast Texas	Tyler	Texas
United States	Wenatchee Valley Medical Center SC-2	Wenatchee	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  Czechia,  France,  Germany,  Greece,  Hong Kong,  Hungary,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Lebanon,  Mexico,  Netherlands,  Peru,  Romania,  Russian Federation,  Spain,  Sweden,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS) Per Investigator Assessment in the PIK3CA Mutant Cohort	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	Once approximately 243 PFS events in this cohort had been observed, up to 32 months
Secondary	Overall Survival (OS) for Patients With PI3KCA Mutant Status	OS is defined as the time from date of randomization to date of death due to any cause.	Up to approximatly 59 months
Secondary	Overall Response Rate (ORR)	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.	Up to approximatly 36 months
Secondary	Time to Definitive Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status	Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)	Baseline, Up to approximatly 36 months
Secondary	Safety and Tolerability of Alpelisib in Combination With Fulvestrant	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.	Up to approximatly 37 months
Secondary	Time to 10% Deterioration in the Global Health Status/Quality of Life (QOL) Scale Score of the EORTC QLQ-C30	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	Up to approximatly 36 months
Secondary	Plasma Concentration-time Profile of Alpelisib Given in Combinatio With Fulvestrant and Appropriate Pharmacokinetics (PK) Parameters	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	Day 8 and Day 15 of Cycle 1, then Day 1 of Cycles 2,4, 6, 8
Secondary	PFS Based on Radiology Assessments and Using RECIST 1.1 Criteria	PFS in patients with PIK3CA mutant status and patients with PIK3CA non-mutant status as measured in ctDNA.	Baseline, Up to approximatly 36 months
Secondary	Clinical Benefit Rate (CBR)	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.	Up to approximatly 36 months
Secondary	Change in the Global Health Status/(QOL) Scale Score of the EORTC QLQ-C30	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	Baseline, Up to approximatly 36 months
Secondary	Summary Statistics of Fulvestrant and Alpelisib Plasma Concentrations	Assessment of any potential impact of fulvestrant on the pharmacokinetics of alpelisib by collection of sparse and trough PK samples.	Day 8 and Day 15 of Cycle 1, then Day 1 of Cycles 2,4, 6, 8
Secondary	PFS for Patients With PIK3CA Non-mutant Status	PFS based on local radiology assessments and using RECIST 1.1 criteria in the PIK3CA non-mutant cohort	Up to approximatly 36 months
Secondary	OS for Patients With PIK3CA Non-mutant Status	OS is defined as the time from date of randomization to date of death due to any cause.	Up to approximatly 59 months