A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT04191499
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study will evaluate the efficacy, safety, and pharmacokinetics of inavolisib in combination with palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant in participants with PIK3CA-mutant, hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 325
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Inavolisib + Palbociclib + Fulvestrant Inavolisib Participants will receive inavolisib, palbociclib, and fulvestrant. Inavolisib + Palbociclib + Fulvestrant Palbociclib Participants will receive inavolisib, palbociclib, and fulvestrant. Inavolisib + Palbociclib + Fulvestrant Fulvestrant Participants will receive inavolisib, palbociclib, and fulvestrant. Placebo + Palbociclib + Fulvestrant Placebo Participants will receive placebo, palbociclib, and fulvestrant. Placebo + Palbociclib + Fulvestrant Palbociclib Participants will receive placebo, palbociclib, and fulvestrant. Placebo + Palbociclib + Fulvestrant Fulvestrant Participants will receive placebo, palbociclib, and fulvestrant.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Up to 3.7 years PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 or death from any cause (whichever occurs first). Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of one or more new lesions was also considered progression. Data for participants without the occurrence of PD or death as of the clinical cutoff date (CCOD) were censored at the time of the last tumor assessment prior to the CCOD. Median PFS was calculated using the Kaplan-Meier methodology.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Objective Response Rate (ORR) Up to approximately 6 years ORR is defined as the percentage of participants with a complete response (CR) and/or partial response (PR) on at least two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR is defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline.
Percentage of Participants With Best Overall Response Rate (BOR) Up to approximately 6 years BOR is defined as the percentage of participants with a CR or PR, as determined by the investigator according to RECIST v1.1. CR is defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline.
Duration of Response (DOR) Up to approximately 6 years DOR is defined as the time from the first occurrence of a CR or PR to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). CR is defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Percentage of Participants With Clinical Benefit Rate (CBR) Up to approximately 6 years CBR is defined as the percentage of participants with a CR, PR, and/or stable disease (SD) for at least 24 weeks, as determined by the investigator according to RECIST v1.1. CR= disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline. PD=at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum in the study.
Overall Survival (OS) Up to approximately 6 years OS is defined as the time from randomization to death from any cause.
Time to Deterioration (TTD) in Pain From randomization to first documentation of a ≥ 2-point increase (Up to approximately 6 years) TTD in pain is defined as the time from randomization to the first documentation of a ≥ 2-point increase from baseline on the "worst pain" item from the Brief Pain Inventory-Short Form (BPI-SF). BPI-SF is a self-administered questionnaire in which the participant was asked to rate severity on a 10-point scale where 0 represents 'No pain/No interference' and 10 represents 'Pain/Interference as bad as you can imagine'. A ≥2-point change is defined as clinically meaningful difference.
TTD in Physical Function (PF) Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years) (Cycle length = 28 days)] TTD in physical function is defined as the time from randomization to the first documentation of a ≥ 10-point decrease from baseline held for two consecutive cycles or initial decrease followed by death or treatment discontinuation within three weeks of last assessment in the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30) PF scale (items 1-5). A ≥10-point change is defined as a clinically meaningful difference. EORTC QLQ-C30 is a cancer-specific health-related quality-of life (QoL) questionnaire with 30 questions. For the PF scale, participant responses to 5 questions about daily activities (strenuous activities, long walks, short walks, bed/chair rest \& needing help with eating, dressing, washing themselves, or using the toilet) is scored on a 4-point scale (1=Not at All to 4=Very Much). Scores are linearly transformed on a scale of 0 to 100, with a high score indicating worst functioning.
TTD in Role Function (RF) Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years) (Cycle length = 28 days)] TTD in Role Function is defined as the time from randomization to the first documentation of a ≥ 10-point decrease from baseline held for two consecutive cycles, or initial decrease followed by death or treatment discontinuation within three weeks of last assessment in the EORTC QLQ-C30 RF scale (items 6 and 7). A ≥10-point change is defined as clinically meaningful difference. EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. For the role functioning scale, participant responses to the 2 questions "Q6: Were you limited in doing either your work or daily activities" and "Q7: Were you limited in pursuing your hobbies or other leisure time activities" were scored on a 4-point scale (1=Not at All to 4=Very Much). The scores were linearly transformed on a scale of 0 to 100, with a low score indicating better functioning.
TTD in Global Health Status (GHS) Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years) (Cycle length = 28 days)] TTD in (GHS)/health-related quality of life (HRQoL) is defined as the time from randomization to the first documentation of a ≥ 10-point decrease from baseline held for two consecutive cycles, or initial decrease followed by death or treatment discontinuation within three weeks of last assessment in the EORTC QLQ-30 GHS/HRQoL scale. A ≥10-point change is defined as clinically meaningful difference. EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. Participant responses to the questions regarding Global Health Status (Q29: GHS; "How would you rate your overall health during the past week?") and Quality of Life (Q30: QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better outcome.
Number of Participants With Adverse Events (AEs) Up to approximately 6 years An AE is an untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with this treatment. An AE can therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product.
Plasma Concentration of Inavolisib Predose on Cycle 1 Days 1, 8 and 15 and Cycle 2 Day 15; 3 hours post-dose on Cycle 1 Days 1 and 15 (Cycle length = 28 days) Plasma Concentration of Palbociclib Predose on Cycle 1 Days 1, 8 and 15 and Cycle 2 Day 15; 3 hours post-dose on Cycle 1 Days 1 and 15 (Cycle length = 28 days) Plasma Concentration of Fulvestrant Predose on Cycle 1 Days 1, 8 and 15 and Cycle 2 Day 15; 3 hours post-dose on Cycle 1 Days 1 and 15 (Cycle length = 28 days)
Trial Locations
- Locations (138)
Hopital du Saint Sacrement
🇨🇦Quebec City, Quebec, Canada
Beijing Cancer Hospital
🇨🇳Beijing, China
The First Hospital of Jilin University
🇨🇳Changchun City, China
West China Hospital, Sichuan University
🇨🇳Chengdu, China
The First Affiliated Hospital, Chongqing Medical University
🇨🇳Chongqing, China
Fujian Medical University Union Hospital
🇨🇳Fujian, China
Sun Yet-sen University Cancer Center
🇨🇳Guangzhou, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet
🇭🇺Szolnok, Hungary
Azienda Ospedaliera Universitaria Federico II
🇮🇹Napoli, Campania, Italy
A.O. Universitaria Di Parma
🇮🇹Parma, Emilia-Romagna, Italy
Az. Osp. Spedali Civili
🇮🇹Brescia, Lombardia, Italy
Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad
🇵🇱Warszawa, Poland
Centro Clinico Champalimaud
🇵🇹Lisboa, Portugal
IPO do Porto
🇵🇹Porto, Portugal
Regional Clinical Oncology Hospital
🇷🇺Yaroslavl, Russian Federation
National Cancer Centre
🇸🇬Singapore, Singapore
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Clinica Universitaria de Navarra
🇪🇸Pamplona, Navarra, Spain
ME Kryviy Rih Oncology Dispensary of Dnipropetrovs?k Regional Council
🇺🇦Kryvyi Rih, Ukraine
Kyiv City Clinical Oncological Center
🇺🇦Kyiv, Ukraine
Royal Marsden Hospital - Fulham
🇬🇧London, United Kingdom
Mount Vernon Hospital
🇬🇧Northwood, United Kingdom
Churchill Hospital
🇬🇧Oxford, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom
Royal Marsden Hosp NHS Fnd
🇬🇧Sutton, United Kingdom
First Affiliated Hospital of Medical College of Xi'an Jiaotong University
🇨🇳Xi'an, China
Henan Cancer Hospital
🇨🇳Zhengzhou, China
Vejle Sygehus
🇩🇰Vejle, Denmark
Centre Jean Perrin Centre Regional de Lutte Contre Le Cancer D auvergne
🇫🇷Clermont-ferrand, France
Centre Georges Francois Leclerc
🇫🇷Dijon, France
Centre Oscar Lambret
🇫🇷Lille, France
Hopital Dupuytren
🇫🇷Limoges, France
Hopital Prive Jean Mermoz
🇫🇷Lyon, France
Institut régional du Cancer Montpellier
🇫🇷Montpellier, France
Institut Universitaire du Cancer de Toulouse-Oncopole
🇫🇷Toulouse, France
Israel-Georgian Medical Research Clinic Healthycore
🇬🇪Tbilisi, Georgia
Tbilisi Oncology Dispensary
🇬🇪Tbilisi, Georgia
Ambulantes Tumorzentrum Spandau
🇩🇪Berlin, Germany
Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH
🇩🇪Essen, Germany
Nationales Centrum für Tumorerkrankungen (NCT)
🇩🇪Heidelberg, Germany
Universitätsklinikum Mannheim
🇩🇪Mannheim, Germany
Klinikum Mutterhaus der Borromaeerinnen gGmbH
🇩🇪Trier, Germany
Universitätsfrauenklinik Ulm
🇩🇪Ulm, Germany
Anticancer Hospital Ag. Savas
🇬🇷Athens, Greece
Univ General Hosp Heraklion
🇬🇷Heraklion, Greece
Euromedical General Clinic of Thessaloniki
🇬🇷Thessaloniki, Greece
European Interbalkan Medical Center
🇬🇷Thessaloniki, Greece
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Tianjin Cancer Hospital
🇨🇳Tianjin, China
Hubei Cancer Hospital
🇨🇳Wuhan, China
Beverly Hills Cancer Center
🇺🇸Beverly Hills, California, United States
Massachusetts General Hospital.
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Sarah Cannon Research Institute / Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Texas Oncology - Central South
🇺🇸Austin, Texas, United States
Texas Tech University Health Sciences Center
🇺🇸El Paso, Texas, United States
Texas Oncology - Northeast Texas
🇺🇸Tyler, Texas, United States
Northwest Medical Specialties
🇺🇸Tacoma, Washington, United States
Fundación CENIT para la Investigación en Neurociencias
🇦🇷Buenos Aires, Argentina
Centro Oncologico Korben
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Hosp Provincial D. Centenarios
🇦🇷Rosario, Argentina
Macquarie University Hospital
🇦🇺Macquarie Park, New South Wales, Australia
Southern Medical Day Care Centre
🇦🇺Wollongong, New South Wales, Australia
Mater Adult Hospital
🇦🇺South Brisbane, Queensland, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Western Health
🇦🇺Fitzroy, Victoria, Australia
Peninsula and South Eastern Haematology and Oncology Group
🇦🇺Frankston, Victoria, Australia
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Santa Casa de Misericordia de Porto Alegre
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
🇧🇷Sao Paulo, São Paulo, Brazil
Arthur J.E. Child Comprehensive Cancer Center-Calgary
🇨🇦Calgary, Alberta, Canada
London Regional Cancer Program, London Health Sciences Centre, Baines Centre
🇨🇦London, Ontario, Canada
Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
Princess Margaret Cancer Center
🇨🇦Toronto, Ontario, Canada
Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)
🇨🇳Nanjing City, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai City, China
Hebei Medical University Fourth Hospital
🇨🇳Shijiazhuang, China
Prince of Wales Hospital
🇭🇰Shatin, Hong Kong
Orszagos Onkologiai Intezet
🇭🇺Budapest, Hungary
Uzsoki Utcai Korhaz
🇭🇺Budapest, Hungary
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Lombardia, Italy
Ospedale Santa Maria Annunziata
🇮🇹Bagno a Ripoli, Toscana, Italy
IOV - Istituto Oncologico Veneto - IRCCS
🇮🇹Padova, Veneto, Italy
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Kyungpook National University Medical Center
🇰🇷Daegu, Korea, Republic of
National Cancer Center
🇰🇷Gyeonggi-do, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-do, 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
Ewha Womans University Mokdong Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
National Cancer Institute IKN
🇲🇾Putrajaya, Federal Territory OF Putrajaya, Malaysia
Hospital Sultan Ismail
🇲🇾Johor Bahru, Malaysia
Sarawak General Hospital
🇲🇾Sarawak, Malaysia
Palmerston North Hospital
🇳🇿Palmerston North, New Zealand
Narodowy Instytut Onkologii Odzia? w Gliwicach
🇵🇱Gliwice, Poland
Przychodnia Lekarska KOMED, Roman Karaszewski
🇵🇱Konin, Poland
Moscow Clinical Scientific Center
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
Blokhin Cancer Research Center
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
LLC Medscan
🇷🇺Moskva, Moskovskaja Oblast, Russian Federation
Clinical Hospital Lapino (LLC Haven)
🇷🇺Yudino, Moskovskaja Oblast, Russian Federation
Medical Clinic "AB Medical group"
🇷🇺Saint Petersburg, Sankt Petersburg, Russian Federation
Volgograd Regional Clinical Oncology Dispensary
🇷🇺Volgograd, Russian Federation
Hospital Universitario de Canarias
🇪🇸La Laguna, Tenerife, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Vall d?Hebron Institute of Oncology (VHIO), Barcelona
🇪🇸Barcelona, Spain
Insituto Catalán de Oncologia (ICO)
🇪🇸Barcelona, Spain
Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico
🇪🇸Jaen, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Clinica Universidad de Navarra-Madrid
🇪🇸Madrid, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Puerta de Hierro
🇪🇸Madrid, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Instituto Valenciano Oncologia
🇪🇸Valencia, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Kaohsiung Medical Uni Chung-Ho Hospital
🇨🇳Kaohsiung, Taiwan
Veterans General Hospital
🇨🇳Taipei, Taiwan
National Taiwan Uni Hospital
🇨🇳Taipei, Taiwan
Koo Foundation Sun Yat-Sen Cancer Center
🇨🇳Taipei, Taiwan
Tri-Service General Hospital, Division of General Surgery
🇨🇳Taipei, Taiwan
Ramathibodi Hospital
🇹🇭Bangkok, Thailand
Maharaj Nakorn Chiang Mai Hospital
🇹🇭Chiang Mai, Thailand
Chulabhorn Hospital
🇹🇭Lak Si, Thailand
Songklanagarind Hospital
🇹🇭Songkhla, Thailand
Adana Baskent University Hospital
🇹🇷Adana, Turkey
Gulhane Training and Research Hospital
🇹🇷Ankara, Turkey
Ege University Medical Faculty
🇹🇷Bornova, ?zm?r, Turkey
Istanbul University Cerrahpasa Faculty of Medicine
🇹🇷Istanbul, Turkey
SI Institute of general&urgent surgery n/a Zaytseva V.T NAMSU
🇺🇦Kharkiv, Kharkiv Governorate, Ukraine
Municipal Institution SubCarpathian Clinical Oncological Centre
🇺🇦Ivano-Frankivsk, KIEV Governorate, Ukraine
Uzhhorod Central City Clinical Hospital
🇺🇦Uzhhorod, KIEV Governorate, Ukraine
City Clinical Hospital #4
🇺🇦Dnipropetrovsk, Ukraine