Clinical trial NCT04191499: 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
Official title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Inavolisib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2019-12-09
Enrollment: 325
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria

* Confirmed diagnosis of HR+/HER2- breast cancer
* Metastatic or locally advanced disease not amenable to curative therapy
* Progression of disease during adjuvant endocrine treatment or within 12 months of completing adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen
* Receiving LHRH agonist therapy for at least 2 weeks prior to Day 1 of Cycle 1 if pre/peri-menopausal
* Confirmation of biomarker eligibility (detection of specified mutation(s) of PIK3CA via specified test)
* Consent to provide fresh or archival tumor tissue specimen
* Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1); evaluable "bone-only" disease is not eligible; "bone-only" disease with at least one measurable, soft-tissue component, even if considered disease that is limited to bone but has lytic or mixed lytic/blastic lesions and at least one measurable soft-tissue component per RECIST v1.1 may be eligible
* Eastern Cooperative Oncology Group Performance Status of 0 or 1
* Life expectancy of \> 6 months
* Adequate hematologic and organ function within 14 days prior to initiation of study treatment

Exclusion Criteria

* Metaplastic breast cancer
* Any history of leptomeningeal disease or carcinomatous meningitis
* Any prior systemic therapy for metastatic breast cancer
* Prior treatment with fulvestrant or any selective estrogen-receptor degrader, with the exception of participants that have received fulvestrant or any selective estrogen-receptor degrader as part of neoadjuvant therapy only and with treatment duration of no longer than 6 months
* Prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway
* Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
* Known and untreated, or active CNS metastases. Patients with a history of treated CNS metastases may be eligible
* Active inflammatory or infectious conditions in either eye, or any eye conditions expected to require surgery during the study treatment period
* Symptomatic active lung disease, or requiring daily supplemental oxygen
* History of inflammatory bowel disease or active bowel inflammation
* Anti-cancer therapy within 2 weeks before study entry
* Investigational drug(s) within 4 weeks before randomization
* Prior radiotherapy to \>= 25% of bone marrow, or hematopoietic stem cell or bone marrow transplantation
* Chronic corticosteroid therapy or immunosuppressants
* Pregnant, lactating, or breastfeeding, or intending to become pregnant during the study or within 2 weeks after the final dose of study treatment
* Major surgical procedure, or significant traumatic injury, within 28 days prior to Day 1 of Cycle 1

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Up to 3.7 years
Secondary outcomes:
measure: Percentage of Participants With Objective Response Rate (ORR)
timeFrame: Up to approximately 6 years
measure: Percentage of Participants With Best Overall Response Rate (BOR)
timeFrame: Up to approximately 6 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 6 years
measure: Percentage of Participants With Clinical Benefit Rate (CBR)
timeFrame: Up to approximately 6 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 6 years
measure: Time to Deterioration (TTD) in Pain
timeFrame: From randomization to first documentation of a ≥ 2-point increase (Up to approximately 6 years)
measure: TTD in Physical Function (PF)
timeFrame: 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)]
measure: TTD in Role Function (RF)
timeFrame: 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)]
measure: TTD in Global Health Status (GHS)
timeFrame: 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)]
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to approximately 6 years
measure: Plasma Concentration of Inavolisib
timeFrame: 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)
measure: Plasma Concentration of Palbociclib
timeFrame: 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)
measure: Plasma Concentration of Fulvestrant
timeFrame: 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)
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital.
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chattanooga
country: United States
facility: Sarah Cannon Research Institute / Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute / Tennessee Oncology
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - Central South
state: Texas
city: El Paso
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Northeast Texas
state: Texas
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Buenos Aires
country: Argentina
facility: Fundación CENIT para la Investigación en Neurociencias
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Centro Oncologico Korben
city: Rosario
country: Argentina
facility: Hosp Provincial D. Centenarios
city: Macquarie Park
country: Australia
facility: Macquarie University Hospital
state: New South Wales
city: Wollongong
country: Australia
facility: Southern Medical Day Care Centre
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Adult Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Fitzroy
country: Australia
facility: Western Health
state: Victoria
city: Frankston
country: Australia
facility: Peninsula and South Eastern Haematology and Oncology Group
state: Victoria
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Porto Alegre
country: Brazil
facility: Santa Casa de Misericordia de Porto Alegre
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
state: São Paulo
city: Calgary
country: Canada
facility: Arthur J.E. Child Comprehensive Cancer Center-Calgary
state: Alberta
city: London
country: Canada
facility: London Regional Cancer Program, London Health Sciences Centre, Baines Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Quebec City
country: Canada
facility: Hopital du Saint Sacrement
state: Quebec
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Changchun City
country: China
facility: The First Hospital of Jilin University
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Chongqing
country: China
facility: The First Affiliated Hospital, Chongqing Medical University
city: Fujian
country: China
facility: Fujian Medical University Union Hospital
city: Guangzhou
country: China
facility: Sun Yet-sen University Cancer Center
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Nanjing City
country: China
facility: Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)
city: Shanghai City
country: China
facility: Fudan University Shanghai Cancer Center
city: Shijiazhuang
country: China
facility: Hebei Medical University Fourth Hospital
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Wuhan
country: China
facility: Hubei Cancer Hospital
city: Xi'an
country: China
facility: First Affiliated Hospital of Medical College of Xi'an Jiaotong University
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Vejle
country: Denmark
facility: Vejle Sygehus
city: Clermont-ferrand
country: France
facility: Centre Jean Perrin Centre Regional de Lutte Contre Le Cancer D auvergne
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Lille
country: France
facility: Centre Oscar Lambret
city: Limoges
country: France
facility: Hopital Dupuytren
city: Lyon
country: France
facility: Hopital Prive Jean Mermoz
city: Montpellier
country: France
facility: Institut régional du Cancer Montpellier
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse-Oncopole
city: Tbilisi
country: Georgia
facility: Israel-Georgian Medical Research Clinic Healthycore
city: Tbilisi
country: Georgia
facility: Tbilisi Oncology Dispensary
city: Berlin
country: Germany
facility: Ambulantes Tumorzentrum Spandau
city: Essen
country: Germany
facility: Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH
city: Heidelberg
country: Germany
facility: Nationales Centrum für Tumorerkrankungen (NCT)
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim
city: Trier
country: Germany
facility: Klinikum Mutterhaus der Borromaeerinnen gGmbH
city: Ulm
country: Germany
facility: Universitätsfrauenklinik Ulm
city: Athens
country: Greece
facility: Anticancer Hospital Ag. Savas
city: Heraklion
country: Greece
facility: Univ General Hosp Heraklion
city: Thessaloniki
country: Greece
facility: Euromedical General Clinic of Thessaloniki
city: Thessaloniki
country: Greece
facility: European Interbalkan Medical Center
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet
city: Budapest
country: Hungary
facility: Uzsoki Utcai Korhaz
city: Szolnok
country: Hungary
facility: Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
state: Campania
city: Parma
country: Italy
facility: A.O. Universitaria Di Parma
state: Emilia-Romagna
city: Brescia
country: Italy
facility: Az. Osp. Spedali Civili
state: Lombardia
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
state: Lombardia
city: Bagno a Ripoli
country: Italy
facility: Ospedale Santa Maria Annunziata
state: Toscana
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto - IRCCS
state: Veneto
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Medical Center
city: Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Mokdong Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Putrajaya
country: Malaysia
facility: National Cancer Institute IKN
state: Federal Territory OF Putrajaya
city: Johor Bahru
country: Malaysia
facility: Hospital Sultan Ismail
city: Sarawak
country: Malaysia
facility: Sarawak General Hospital
city: Palmerston North
country: New Zealand
facility: Palmerston North Hospital
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii Odzia? w Gliwicach
city: Konin
country: Poland
facility: Przychodnia Lekarska KOMED, Roman Karaszewski
city: Warszawa
country: Poland
facility: Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad
city: Lisboa
country: Portugal
facility: Centro Clinico Champalimaud
city: Porto
country: Portugal
facility: IPO do Porto
city: Moscow
country: Russian Federation
facility: Moscow Clinical Scientific Center
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: Blokhin Cancer Research Center
state: Moskovskaja Oblast
city: Moskva
country: Russian Federation
facility: LLC Medscan
state: Moskovskaja Oblast
city: Yudino
country: Russian Federation
facility: Clinical Hospital Lapino (LLC Haven)
state: Moskovskaja Oblast
city: Saint Petersburg
country: Russian Federation
facility: Medical Clinic "AB Medical group"
state: Sankt Petersburg
city: Volgograd
country: Russian Federation
facility: Volgograd Regional Clinical Oncology Dispensary
city: Yaroslavl
country: Russian Federation
facility: Regional Clinical Oncology Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias
state: Tenerife
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Vall d?Hebron Institute of Oncology (VHIO), Barcelona
city: Barcelona
country: Spain
facility: Insituto Catalán de Oncologia (ICO)
city: Jaen
country: Spain
facility: Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra-Madrid
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Instituto Valenciano Oncologia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical Uni Chung-Ho Hospital
city: Taipei
country: Taiwan
facility: Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan Uni Hospital
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital, Division of General Surgery
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital
city: Lak Si
country: Thailand
facility: Chulabhorn Hospital
city: Songkhla
country: Thailand
facility: Songklanagarind Hospital
city: Adana
country: Turkey
facility: Adana Baskent University Hospital
city: Ankara
country: Turkey
facility: Gulhane Training and Research Hospital
city: Bornova, ?zm?r
country: Turkey
facility: Ege University Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Faculty of Medicine
city: Kharkiv
country: Ukraine
facility: SI Institute of general&urgent surgery n/a Zaytseva V.T NAMSU
state: Kharkiv Governorate
city: Ivano-Frankivsk
country: Ukraine
facility: Municipal Institution SubCarpathian Clinical Oncological Centre
state: KIEV Governorate
city: Uzhhorod
country: Ukraine
facility: Uzhhorod Central City Clinical Hospital
state: KIEV Governorate
city: Dnipropetrovsk
country: Ukraine
facility: City Clinical Hospital #4
city: Kryvyi Rih
country: Ukraine
facility: ME Kryviy Rih Oncology Dispensary of Dnipropetrovs?k Regional Council
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Oncological Center
city: London
country: United Kingdom
facility: Royal Marsden Hospital - Fulham
city: Northwood
country: United Kingdom
facility: Mount Vernon Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Hosp NHS Fnd
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: