A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT05646862
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This is a Phase III, multicenter, randomized, open-label, global study designed to evaluate the efficacy and safety of inavolisib plus fulvestrant compared with alpelisib plus fulvestrant in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2) -negative, PIK3CA-mutated, locally advanced (LA) or metastatic breast cancer (mBC), who progressed during or after cyclin dependent kinase 4/6i (CDK4/6i)-based therapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 400
- If pre/perimenopausal women and men treatment with luteinizing hormone-releasing hormone (LHRH) agonist therapy beginning at least 2 weeks prior to Day 1 of Cycle 1
- Histologically or cytologically confirmed adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to surgical or radiation therapy with curative intent
- Documented HR +/ HER2- tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines
- Confirmation of biomarker eligibility: detection of specified mutation(s) of PIK3CA via specified test
- Disease progression after or during treatment with a combination of CDK4/6i and endocrine therapy: <= 2 prior lines of systemic therapy in mBC setting; CDK4/6i based therapy does not need to be the last one received prior study entry; one line of chemotherapy in mBC setting allowed
- Measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
- Participants for whom endocrine-based therapy is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study, as per national or local treatment guidelines
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- Life expectancy of > 6 months
- Adequate hematologic and organ function prior to initiation of study treatment
- Metaplastic breast cancer
- Prior treatment in locally advanced or metastatic setting with any PI3K, AKT, or mTOR inhibitor or any agent whose mechanism of action is to inhibit the PI3K/-AKT/-mTOR pathway
- Participant who relapsed with documented evidence of progression > 12 months from completion of adjuvant CDK4/6i based therapy with no treatment for metastatic disease
- Pregnant, lactating, or breastfeeding, or intending to become pregnant during the study or at least 60 days after the final dose of study treatment
- Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
- Inability or unwillingness to swallow pills
- Malabsorption syndrome or other condition that would interfere with enteral absorption
- Any history of leptomeningeal disease or carcinomatous meningitis
- Known and untreated, or active central nervous system (CNS) metastases. Participants with a history of treated CNS metastases are eligible if they meet specific certain criteria
- Known active, systemic infection at study enrollment, or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization within 7 days prior to Day 1 of Cycle 1
- Any concurrent ocular or intraocular condition that, in the opinion of the investigator, would require medical or surgical intervention during the study period to prevent or treat vision loss that might result from that condition
- Active inflammatory or infectious conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye
- Requirement for daily supplemental oxygen
- Symptomatic active lung disease, including pneumonitis
- History of or active inflammatory bowel disease
- Any active bowel inflammation
- Clinically significant and active liver disease, including severe liver impairment, viral or other hepatitis, current alcohol abuse, or cirrhosis
- Participants with known human immunodeficiency virus infection that meet specific criteria
- Investigational drug(s) within 4 weeks before randomization or within 5 half-lives of the investigational drug(s), whichever is longer
- History of other malignancy within 5 years prior to screening, except for cancers with very low risk of recurrence
- Chronic therapy of >= 10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressants for a chronic disease
- Allergy or hypersensitivity to components or excipients of the inavolisib, fulvestrant, or alpelisib formulations
- History of severe cutaneous reactions like Stevens-Johnson Syndrome, Erythema Multiforme, Toxic Epidermal Necrolysis, or Drug Reaction with Eosinphilia and Systemic Symptoms
- Active ongoing osteonecrosis of the jaw
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Inavolisib + Fulvestrant Inavolisib Participants will be administered the treatments as outlined in the interventions section. Inavolisib + Fulvestrant Fulvestrant Participants will be administered the treatments as outlined in the interventions section. Alpelisib + Fulvestrant Fulvestrant Participants will be administered the treatments as outlined in the interventions section. Alpelisib + Fulvestrant Alpelisib Participants will be administered the treatments as outlined in the interventions section.
- Primary Outcome Measures
Name Time Method Blinded Independent Central Review (BICR)-Assessed Progression Free Survival (PFS) From randomization until disease progression or death due to any cause (up to approximately 64 months)
- Secondary Outcome Measures
Name Time Method TTCD in Physical Functioning Day 1 of Cycles 1 and 2 and beyond, 30-day safety follow up visit, post-treatment tumor assessment follow-up with PRO collection and survival follow up visit (up to approximately 85 months). Each cycle is 28 days. Percentage of Participants with Adverse Events Day 1 until 30 days after the final dose of study treatment (up to approximately 85 months) Plasma Concentration of Inavolisib at Specified Timepoints Day 1 and 15 of Cycle 1, and Day 1 of Cycles 2 and 3. Each cycle is 28 days. TTCD in Global Health Status/Quality of Life (QOL) Day 1 of Cycles 1 and 2 and beyond, 30-day safety follow up visit, post-treatment tumor assessment follow-up with PRO collection and survival follow up visit (up to approximately 85 months). Each cycle is 28 days. BICR-Assessed Duration of Response (DOR) From CR or PR until disease progression or death due to any cause (up to approximately 64 months) Time to Confirmed Deterioration (TTCD) in Pain Day 1 of Cycles 1 and 2 and beyond, 30-day safety follow up visit, post-treatment tumor assessment follow-up with PRO collection and survival follow up visit (up to approximately 85 months). Each cycle is 28 days. Overall survival (OS) From randomization until death due to any cause (up to approximately 85 months) BICR-Assessed Overall Response Rate (ORR) Up to approximately 64 months BICR-Assessed Best Overall Response (BOR) Up to approximately 64 months BICR-Assessed Clinical Benefit Rate (CBR) Up to approximately 64 months TTCD in Role Functioning Day 1 of Cycles 1 and 2 and beyond, 30-day safety follow up visit, post-treatment tumor assessment follow-up with PRO collection and survival follow up visit (up to approximately 85 months). Each cycle is 28 days.
Trial Locations
- Locations (183)
Clinica Viedma S.A.
🇦🇷Viedma, Argentina
The Second Affiliated Hospital of Zhejiang University School of Medicine
🇨🇳Hangzhou City, China
Sir Run Run Shaw Hospital Zhejiang University
🇨🇳Hangzhou City, China
Harbin Medical University Tumor Hospital
🇨🇳Harbin, China
Shandong Cancer Hospital
🇨🇳Jinan, China
The Second Affiliated Hospital to Nanchang University
🇨🇳Nanchang, China
Jiangsu Cancer Hospital
🇨🇳Nanjing City, China
Tianjin Cancer Hospital
🇨🇳Tianjin, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan City, China
Hubei Cancer Hospital
🇨🇳Wuhan, China
Ege Uni Medical Faculty Hospital
🇹🇷Izmir, Turkey
Cancer Blood and Specialty Clinic
🇺🇸Los Alamitos, California, United States
Los Angeles Cancer Network
🇺🇸Los Angeles, California, United States
UC Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
Eastern CT Hematology and Oncology Associates
🇺🇸Norwich, Connecticut, United States
Cancer Care Centers of Brevard
🇺🇸Palm Bay, Florida, United States
Cleveland Clinic Florida
🇺🇸Weston, Florida, United States
Grady Health System
🇺🇸Atlanta, Georgia, United States
Midtown West Medical
🇺🇸Atlanta, Georgia, United States
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
Winship Cancer Institute at Emory Saint Joseph's Hospital
🇺🇸Atlanta, Georgia, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Karmanos Cancer Institute.
🇺🇸Detroit, Michigan, United States
Cancer & Hematology Centers of Western Michigan
🇺🇸Grand Rapids, Michigan, United States
Minnesota Oncology Hematology
🇺🇸Saint Paul, Minnesota, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
Asante Rogue Regional Medical Center
🇺🇸Medford, Oregon, United States
WellSpan Oncology Research
🇺🇸York, Pennsylvania, United States
Texas Oncology - Dallas Presbyterian Hospital
🇺🇸Dallas, Texas, United States
Texas Tech University Health Sciences Center
🇺🇸El Paso, Texas, United States
Fundación CENIT para la Investigación en Neurociencias
🇦🇷Buenos Aires, Argentina
Centro Oncologico Korben
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Fundacion CORI para la Investigacion y Prevencion del Cancer
🇦🇷La Rioja, Argentina
Instituto de Oncología de Rosario
🇦🇷Rosario, Argentina
Sanatorio Parque S.A.
🇦🇷Rosario, Argentina
Hosp Provincial D. Centenarios
🇦🇷Rosario, Argentina
CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
🇦🇷San Juan, Argentina
Campbelltown Hospital
🇦🇺Campbelltown, New South Wales, Australia
Coffs Harbour Health Campus
🇦🇺Coffs Harbour, New South Wales, Australia
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Kinghorn Cancer Centre
🇦🇺Darlinghurst, New South Wales, Australia
Gosford Hospital
🇦🇺Gosford, New South Wales, Australia
Icon Cancer Care Wesley
🇦🇺Auchenflower, Queensland, Australia
University of the Sunshine Coast
🇦🇺Sippy Downs, Queensland, Australia
Bendigo Cancer Centre
🇦🇺Bendigo, Victoria, Australia
Sir Charles Gairdner Hospital
🇦🇺Perth, Western Australia, Australia
Cliniques Universitaires St-Luc
🇧🇪Bruxelles, Belgium
GHdC Site Les Viviers
🇧🇪Charleroi, Belgium
UZ Antwerpen
🇧🇪Edegem, Belgium
UZ Gent
🇧🇪Gent, Belgium
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Clinique Ste-Elisabeth
🇧🇪Namur, Belgium
Hospital da Bahia
🇧🇷Salvador, Bahia, Brazil
NUPEC
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Hospital Santa Cruz / Centro de Oncologia D'Or
🇧🇷Curitiba, Paraná, Brazil
Hospital do Cancer de Pernambuco - HCP
🇧🇷Recife, Pernambuco, Brazil
Instituto D?Or de Pesquisa e Ensino ? Hospital Esperança Recife
🇧🇷Recife, Pernambuco, Brazil
Vencer Oncoclínica - Centro de Pesquisa do Piauí
🇧🇷Teresina, Piauí, Brazil
Liga Norte Riograndense Contra O Câncer
🇧🇷Natal, Rio Grande Do Norte, Brazil
Santa Casa de Misericordia de Porto Alegre
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital Sao Lucas - PUCRS
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital de Base de Sao Jose do Rio Preto
🇧🇷Sao Jose do Rio Preto, São Paulo, Brazil
Hospital Sírio-Libanês
🇧🇷Sao Paulo, São Paulo, Brazil
Arthur J.E. Child Comprehensive Cancer Center-Calgary
🇨🇦Calgary, Alberta, Canada
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
BC Cancer ? Vancouver
🇨🇦Vancouver, British Columbia, Canada
The Moncton Hospital
🇨🇦Moncton, New Brunswick, Canada
Juravinski Hospital
🇨🇦Hamilton, Ontario, Canada
The Ottawa Hospital - General Campus
🇨🇦Ottawa, Ontario, Canada
CIUSSS de l Est de l Ile de Montreal - Hopital Maisonneuve Rosemont
🇨🇦Montreal, Quebec, Canada
Centre Hospitalier de l'Universite de Montreal (CHUM)
🇨🇦Montreal, Quebec, Canada
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Hôpital du Sacré-Coeur de Montreal
🇨🇦Montreal, Quebec, Canada
The First Hospital of Jilin University
🇨🇳Changchun City, China
Sichuan Provincial Cancer Hospital
🇨🇳Chengdu, China
The First Affiliated Hospital, Chongqing Medical University
🇨🇳Chongqing, China
Guangdong Provincial People's Hospital
🇨🇳Guangzhou City, China
Sun yat-sen University Cancer Center
🇨🇳Guangzhou, China
First Affiliated Hospital of Medical College of Xi'an Jiaotong University
🇨🇳Xi'an, China
Zhejiang Cancer Hospital
🇨🇳Zhejiang, China
Institut Sainte Catherine
🇫🇷Avignon, France
Centre Hospitalier de La Cote Basque
🇫🇷Bayonne, France
Polyclinique Bordeaux Nord
🇫🇷Bordeaux, France
Centre Leon Berard
🇫🇷Lyon, France
ICM
🇫🇷Montpellier cedex 5, France
Centre Eugene Marquis
🇫🇷Rennes, France
IUCT Oncopole
🇫🇷Toulouse, France
Uniklinik RWTH Aachen Klinik für Gynäkologie und Geburtsmedizin
🇩🇪Aachen, Germany
Universitätsklinikum Essen
🇩🇪Essen, Germany
Praxis für Interdisziplinäre Onkologie und Hämatologie GbR
🇩🇪Freiburg, Germany
Niels-Stensen-Kliniken Franziskus-Hospital Harderberg GmbH
🇩🇪Georgsmarienhütte, Germany
Universitätsmedizin Göttingen Georg-August-Universität
🇩🇪Göttingen, Germany
Mammazentrum Hamburg am Krankenhaus Jerusalem
🇩🇪Hamburg, Germany
Medizinische Hochschule Zentrum Frauenheilkunde Abt.Gynäkologische Onkologie
🇩🇪Hannover, Germany
Nationales Centrum für Tumorerkrankungen (NCT)
🇩🇪Heidelberg, Germany
Brustzentrum Rhein-Ruhr Servicegesellschaft mbH
🇩🇪Mönchengladbach, Germany
Klinik & Poliklinik für Frauenheilkunde und Geburtshilfe, Campus Innenstadt
🇩🇪München, Germany
St. Vincenz-Krankenhaus GmbH Paderborn Frauen- und Kinderklinik St. Louise
🇩🇪Paderborn, Germany
A.O. S. Anna e San Sebastiano
🇮🇹Caserta, Campania, Italy
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola
🇮🇹Meldola, Emilia-Romagna, Italy
AUSL della Romagna
🇮🇹Ravenna, Emilia-Romagna, Italy
Irccs Centro Di Riferimento Oncologico (CRO)
🇮🇹Aviano, Friuli-Venezia Giulia, Italy
Ospedale San Raffaele
🇮🇹Milano, Lombardia, Italy
Ospedale Di Macerata
🇮🇹Macerata, Marche, Italy
Humanitas Centro Catanese Di Oncologia
🇮🇹Misterbianco (CT), Sicilia, Italy
Ospedale S. Giuseppe
🇮🇹Empoli (FI), Toscana, Italy
Ospedale Santa Chiara
🇮🇹Trento, Trentino-Alto Adige, Italy
Kyungpook National University Chilgok Hospital
🇰🇷Daegu, Korea, Republic of
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
CHA Bundang Medical Center
🇰🇷Gyeonggi-do, Korea, Republic of
Catholic Univ. of Incheon St.Mary's Hospital
🇰🇷Incheon, Korea, Republic of
Inha University Hospital
🇰🇷Incheon, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Gangnam Severance Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul St Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Panamerican Clinical Research S.A de C.V.
🇲🇽Guadalajara, Jalisco, Mexico
Health Pharma Professional Research
🇲🇽Cdmx, Mexico CITY (federal District), Mexico
COI Centro Oncologico Internacional Santa Fe
🇲🇽Ciudad de México, Mexico CITY (federal District), Mexico
OncoMed
🇲🇽Ciudad de México, Mexico CITY (federal District), Mexico
ARKE Estudios Clínicos S.A. de C.V.
🇲🇽Mexico City, Mexico CITY (federal District), Mexico
Instituto Nacional de Cancerologia
🇲🇽Distrito Federal, Mexico
CENEIT Oncologicos
🇲🇽Mexico City, Mexico
Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde
🇲🇽Morelia, Mexico
Centrum Onkologii im. Prof. Franciszka ?ukaszczyka
🇵🇱Bydgoszcz, Poland
Szpital Morski im.PCK
🇵🇱Gdynia, Poland
Narodowy Instytut Onkologii Odzia? w Gliwicach
🇵🇱Gliwice, Poland
Przychodnia Lekarska KOMED, Roman Karaszewski
🇵🇱Konin, Poland
Szpital Wojewódzki im. Miko?aja Kopernika
🇵🇱Koszalin, Poland
Szpital Uniwersytecki w Krakowie
🇵🇱Kraków, Poland
MRUKMED Lekarz Beata Madej-Mruk i Partner Spolka Partnerska Oddzial nr 1 w Rzeszowie
🇵🇱Rzeszow, Poland
Narodowy Instytut Onkologii im. M.Sklodowskiej-Curie
🇵🇱Warszawa, Poland
Dr. W.M. Szpak Incorporated trading as Rainbow Oncology
🇿🇦Durban, South Africa
Hopelands Cancer Centre
🇿🇦Hilton, South Africa
Medical Oncology Centre of Rosebank
🇿🇦Johannesburg, South Africa
Richards Bay Oncology Centre
🇿🇦KwaZulu Natal, South Africa
Mountain View Oncology
🇿🇦Paarl, South Africa
ICO L'Hospitalet
🇪🇸L Hospitalet De Llobregat, Barcelona, Spain
Hospital Universitario de Canarias
🇪🇸La Laguna, Tenerife, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital San Pedro De Alcantara
🇪🇸Caceres, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Regional Universitario Carlos Haya
🇪🇸Malaga, Spain
Hospital Universitario Virgen de Arrixaca
🇪🇸Murcia, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Royal Preston Hosptial
🇬🇧Preston, United Kingdom
China Medical University Hospital
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei City, Taiwan
Chang Gung Memorial Hosipital at Linkou
🇨🇳Taoyuan City, Taiwan
Veterans General Hospital - Taichung
🇨🇳Xitun Dist., Taiwan
National Taiwan University Hospital
🇨🇳Zhongzheng Dist., Taiwan
Chulalongkorn Hospital
🇹🇭Bangkok, Thailand
Maharaj Nakorn Chiang Mai Hospital
🇹🇭ChiangMai, Thailand
Chulabhorn Hospital
🇹🇭Lak Si, Thailand
Songklanagarind Hospital
🇹🇭Songkhla, Thailand
Gulhane Training and Applicaton Hospital
🇹🇷Ankara, Turkey
Memorial Ankara Hastanesi
🇹🇷Ankara, Turkey
Dicle University Faculty of Medicine
🇹🇷Diyarbakir, Turkey
Trakya University Medical Faculty
🇹🇷Edirne, Turkey
Medipol Mega Üniversite Hastanesi Göztepe
🇹🇷Istanbul, Turkey
Marmara Uni Faculty of Medicine
🇹🇷Istanbul, Turkey
Katip Celebi University Ataturk Training and Research Hospital
🇹🇷Izmir, Turkey
Goztepe Prof.Dr. Suleyman Yalcin City Hospital
🇹🇷Kadiköy, Turkey
Medical Park Seyhan Hospital
🇹🇷Seyhan, Turkey
Hacettepe Uni Medical Faculty Hospital
🇹🇷Sihhiye/Ankara, Turkey
Basingstoke and North Hampshire Hospital
🇬🇧Basingstoke, United Kingdom
Blackpool Victoria Hospital
🇬🇧Blackpool, United Kingdom
Dumfries and Galloway Royal Infirmary
🇬🇧Dumfries, United Kingdom
Western General Hospital
🇬🇧Edinburgh, United Kingdom
Princess Alexandra Hospital
🇬🇧Harlow, United Kingdom
St John's Hospital
🇬🇧Livingston, United Kingdom
St Bartholomew's Hospital
🇬🇧London, United Kingdom
Maidstone & Tonbridge Wells Hospital
🇬🇧Maidstone, United Kingdom
Mount Vernon & Watford Trust Hospital
🇬🇧Northwood, United Kingdom
Churchill Hospital
🇬🇧Oxford, United Kingdom
Royal Hampshire County Hospital
🇬🇧Winchester, United Kingdom