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.
NCT ID: NCT02437318
Last Updated: 2025-02-13
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
572 participants
INTERVENTIONAL
2015-07-23
2023-06-09
Brief Summary
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Detailed Description
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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)
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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Fulvestrant + alpelisib
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)
Fulvestrant
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
Alpelisib
300 mg of alpelisib tablets for oral use administered once daily
Fulvestrant + placebo
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)
Fulvestrant
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
Placebo
300 mg of placebo tablets for oral use administered once daily
Interventions
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Fulvestrant
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
Alpelisib
300 mg of alpelisib tablets for oral use administered once daily
Placebo
300 mg of placebo tablets for oral use administered once daily
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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 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.
18 Years
100 Years
ALL
No
Sponsors
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Novartis Pharmaceuticals
INDUSTRY
Responsible Party
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Principal Investigators
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Novartis Pharmaceuticals
Role: STUDY_DIRECTOR
Novartis Pharmaceuticals
Locations
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Novartis Investigative Site
Szekszárd, , Hungary
Ironwood Cancer and Research Centers
Chandler, Arizona, United States
Mayo Clinic Arizona
Scottsdale, Arizona, United States
Highlands Oncology Group
Fayetteville, Arkansas, United States
Beverly Hills Cancer Center
Beverly Hills, California, United States
City of Hope National Medical Center
Duarte, California, United States
Scripps Green Hospital
La Jolla, California, United States
Kaiser Permanent Southern Californi
San Diego, California, United States
UCSF
San Francisco, California, United States
Florida Cancer Specialists
Fort Myers, Florida, United States
Florida Cancer Specialists-North
St. Petersburg, Florida, United States
Rush University Medical Center
Chicago, Illinois, United States
NorthShore University Health System
Evanston, Illinois, United States
Edward Cancer Center
Naperville, Illinois, United States
Fort Wayne Medical Oncology Hematology Inc
Fort Wayne, Indiana, United States
St Francis Health Comprehensive Cancer Center
Topeka, Kansas, United States
Mercy Medical Center
Baltimore, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Lahey Clinic
Burlington, Massachusetts, United States
Detroit Clinical Research Center
Owosso, Michigan, United States
St Lukes Cancer Institute
Kansas City, Missouri, United States
St Vincent Frontier Cancer Center
Billings, Montana, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
University Hospitals of Cleveland Seidman Cancer Center
Cleveland, Ohio, United States
Good Samaritan Regional Medical Center
Corvallis, Oregon, United States
Lancaster General Hospital
Lancaster, Pennsylvania, United States
Prisma Health Upstate
Greenville, South Carolina, United States
Avera Cancer
Sioux Falls, South Dakota, United States
SCRI Oncology Partners
Nashville, Tennessee, United States
Texas Oncology PA Dallas Presbyterian Hospital
Dallas, Texas, United States
El Paso Texas Oncology
El Paso, Texas, United States
Mays Cancer Ctr Uthsa Mdacc
San Antonio, Texas, United States
Texas Oncology Northeast Texas
Tyler, Texas, United States
Virginia Cancer Specialists
Fairfax, Virginia, United States
Wenatchee Valley Medical Center
Wenatchee, Washington, United States
Novartis Investigative Site
Berazategui, Buenos Aires, Argentina
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CABA, Buenos Aires, Argentina
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Rio Negro, Viedma, Argentina
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La Rioja, , Argentina
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Wahroonga, New South Wales, Australia
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Wooloongabba, Queensland, Australia
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Elizabeth Vale, South Australia, Australia
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Melbourne, Victoria, Australia
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Linz, , Austria
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Vienna, , Austria
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Sint-Niklaas, Oost Vlaanderen, Belgium
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Brussels, , Belgium
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Brussels, , Belgium
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Edegem, , Belgium
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Libramont, , Belgium
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Ottignies, , Belgium
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Verviers, , Belgium
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Natal, Rio Grande do Norte, Brazil
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Lajeado, Rio Grande do Sul, Brazil
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São Paulo, São Paulo, Brazil
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São José do Rio Preto, , Brazil
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São Paulo, , Brazil
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Plovdiv, , Bulgaria
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Sofia, , Bulgaria
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Varna, , Bulgaria
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Varna, , Bulgaria
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Calgary, Alberta, Canada
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Cambridge, Ontario, Canada
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Ottawa, Ontario, Canada
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Toronto, Ontario, Canada
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Québec, Quebec, Canada
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Temuco, Región de la Araucanía, Chile
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Santiago, , Chile
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Viña del Mar, , Chile
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Prague, Czech Republic, Czechia
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Zlín, Czech Republic, Czechia
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Hradec Králové, CZE, Czechia
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Prague, , Czechia
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Marseille, Bouches Du Rhone, France
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Angers, , France
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Avignon, , France
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Caen, , France
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Clermont-Ferrand, , France
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Créteil, , France
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La Roche-sur-Yon, , France
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Le Chesnay, , France
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Levallois-Perret, , France
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Lyon 08, , France
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Saint-Herblain, , France
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Toulouse, , France
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Villejuif, , France
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Lübeck, Schleswig-Holstein, Germany
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Aschaffenburg, , Germany
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Frankfurt, , Germany
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Friedrichshafen, , Germany
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Hanover, , Germany
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Homburg, , Germany
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Kiel, , Germany
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Leipzig, , Germany
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Mainz, , Germany
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Potsdam, , Germany
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Recklinghausen, , Germany
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Rostock, , Germany
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Ulm, , Germany
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Velbert, , Germany
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Thessaloniki, GR, Greece
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Athens, , Greece
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Athens, , Greece
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Pokfulam, , Hong Kong
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Budapest, Pest County, Hungary
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Budapest, , Hungary
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Nyíregyháza, , Hungary
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Vijayawada, Andhra Pradesh, India
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Nagpur, Maharashtra, India
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Mumbai, , India
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Beersheba, , Israel
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Haifa, , Israel
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Petah Tikva, , Israel
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Ramat Gan, , Israel
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Tel Aviv, , Israel
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Ancona, AN, Italy
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Chieti, CH, Italy
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Meldola, FC, Italy
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Milan, MI, Italy
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Palermo, PA, Italy
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Padua, PD, Italy
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Pontedera, PI, Italy
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Aviano, PN, Italy
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Rionero in Vulture, PZ, Italy
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Roma, RM, Italy
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Savona, SV, Italy
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Torino, TO, Italy
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Negrar, VR, Italy
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Sassari, , Italy
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Nagoya, Aichi-ken, Japan
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Matsuyama, Ehime, Japan
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Maebashi, Gunma, Japan
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Sapporo, Hokkaido, Japan
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Akashi, Hyōgo, Japan
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Isehara, Kanagawa, Japan
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Yokohama, Kanagawa, Japan
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Osaka, Osaka, Japan
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Osaka, Osaka, Japan
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Kitaadachi-gun, Saitama, Japan
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Chuo Ku, Tokyo, Japan
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Minato Ku, Tokyo, Japan
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Kagoshima, , Japan
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Kumamoto, , Japan
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Beirut, , Lebanon
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El Achrafiyé, , Lebanon
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Saida, , Lebanon
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Monterrey, Nuevo León, Mexico
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San Luis Potosí City, , Mexico
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Venray, CE, Netherlands
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Terneuzen, , Netherlands
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San Borja, Lima region, Peru
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Surquillo, Lima region, Peru
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Lima, , Peru
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Floreşti, Cluj, Romania
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Craiova, Dolj, Romania
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Iași, , Romania
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Arkhangelsk, , Russia
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Ryazan, , Russia
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Saint Petersburg, , Russia
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Bundang Gu, Gyeonggi-do, South Korea
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Gyeonggi-do, Korea, South Korea
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Seoul, , South Korea
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Seoul, , South Korea
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Seoul, , South Korea
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Seoul, , South Korea
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Seville, Andalusia, Spain
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Palma de Mallorca, Balearic Islands, Spain
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Jerez de la Frontera, Cadiz, Spain
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Badalona, Catalonia, Spain
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Barcelona, Catalonia, Spain
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Badajoz, Extremadura, Spain
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Cáceres, Extremadura, Spain
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Santiago de Compostela, Galicia, Spain
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Pozuelo de Alarcón, Madrid, Spain
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El Palmar, Murcia, Spain
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San Cristóbal de La Laguna, Santa Cruz De Tenerife, Spain
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Alicante, Valencia, Spain
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Castellon, Valencia, Spain
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Valencia, Valencia, Spain
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Madrid, , Spain
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Madrid, , Spain
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Madrid, , Spain
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Madrid, , Spain
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Madrid, , Spain
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Gävle, , Sweden
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Örebro, , Sweden
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Västerås, , Sweden
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Taipei, , Taiwan
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Taipei, , Taiwan
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Bangkok, , Thailand
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Bangkok, , Thailand
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Leicester, , United Kingdom
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London, , United Kingdom
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Plymouth, , United Kingdom
Countries
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References
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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.
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.
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.
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.
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.
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.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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2015-000340-42
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
CBYL719C2301
Identifier Type: -
Identifier Source: org_study_id
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