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

Breast Cancer Clinical Trial

— INAVO120  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04191499
• Other study ID #: WO41554
• Secondary ID: 2019-002455-42
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: January 29, 2020
• Est. completion date: September 30, 2030

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 325
• Est. completion date: September 30, 2030
• Est. primary completion date: September 29, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 60 days after the final dose of study treatment

• Major surgical procedure, or significant traumatic injury, within 28 days prior to Day 1 of Cycle 1

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Inavolisib
Participants will receive oral inavolisib on Days 1-28 of each 28-day cycle.
• Placebo
Participants will receive oral placebo on Days 1-28 of each 28-day cycle.
• Palbociclib
Participants will receive oral palbociclib on Days 1-21 of each 28-day cycle.
• Fulvestrant
Participants will receive intramuscular (IM) fulvestrant approximately every 4 weeks.

Locations

Country	Name	City	State
Argentina	Fundación CENIT para la Investigación en Neurociencias	Buenos Aires
Argentina	Centro Oncologico Korben; Oncology	Ciudad Autonoma Buenos Aires
Argentina	Hosp Provincial D. Centenarios; Oncology Dept	Rosario
Argentina	Clinica Viedma S.A.	Viedma
Australia	Western Health	Fitzroy	Victoria
Australia	Peninsula and South Eastern Haematology and Oncology Group	Frankston	Victoria
Australia	Macquarie University Hospital	Macquarie Park	New South Wales
Australia	Mater Adult Hospital; Oncology	South Brisbane	Queensland
Australia	Westmead Hospital; Medical Oncology and Pallative Care	Westmead	New South Wales
Australia	Southern Medical Day Care Centre	Wollongong	New South Wales
Australia	Princess Alexandra Hospital; Cancer Trials Unit	Woolloongabba	Queensland
Belgium	UZ Leuven Gasthuisberg	Leuven
Brazil	Hospital Araujo Jorge; Departamento de Ginecologia E Mama	Goiania	GO
Brazil	Santa Casa de Misericordia de Porto Alegre	Porto Alegre	RS
Brazil	Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda	Sao Paulo	SP
Canada	Tom Baker Cancer Centre-Calgary	Calgary	Alberta
Canada	London Regional Cancer Program, London Health Sciences Centre, Baines Centre	London	Ontario
Canada	Ottawa Hospital	Ottawa	Ontario
Canada	Hopital du Saint Sacrement	Quebec City	Quebec
Canada	Princess Margaret Cancer Center	Toronto	Ontario
China	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	Fuzhou City
China	Sun Yet-sen University Cancer Center	Guangzhou City
China	Zhejiang Cancer Hospital; Zhejiang Cancer Hospital cancer department	Hangzhou City
China	Harbin Medical University Cancer Hospital	Harbin
China	Shandong Cancer Hospital	Jinan
China	Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)	Nanjing City
China	Fudan University Shanghai Cancer Center; Medical Oncology	Shanghai City
China	Hebei Medical University Fourth Hospital;(Tumor Hospital of Hebei Province)	Shijiazhuang
China	Tianjin Cancer Hospital	Tianjin
China	Hubei Cancer Hospital	Wuhan
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City
China	First Affiliated Hospital of Medical College of Xi'an Jiaotong University	Xi'an
China	Henan Cancer Hospital	Zhengzhou
Denmark	Vejle Sygehus; Onkologisk Afdeling	Vejle
France	Centre Jean Perrin Centre Regional de Lutte Contre Le Cancer D auvergne	Clermont-ferrand
France	Centre Georges Francois Leclerc; Oncologie 3	Dijon
France	Centre Oscar Lambret; Senologie	Lille
France	Hopital Dupuytren; Oncologie Medicale	Limoges
France	Hopital Prive Jean Mermoz; Cancerologie	Lyon
France	Institut régional du Cancer Montpellier	Montpellier
France	Institut Universitaire du Cancer de Toulouse-Oncopole	Toulouse
Georgia	Acad. F. Todua Medical Center	Tbilisi
Georgia	Cancer Research Centre	Tbilisi
Georgia	Israel-Georgian Medical Research Clinic Healthycore	Tbilisi
Georgia	Multiprofile Clinic Consilium Medulla	Tbilisi
Georgia	S Khechinashvili University Clinic Ltd	Tbilisi
Georgia	Tbilisi Oncology Dispensary	Tbilisi
Germany	Ambulantes Tumorzentrum Spandau; Dres. Benno Mohr und Uwe Peters	Berlin
Germany	Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum	Essen
Germany	Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum Mannheim; Frauenklinik	Mannheim
Germany	Klinikum Mutterhaus der Borromaeerinnen gGmbH; Haematologie/Onkologie	Trier
Germany	Universitätsfrauenklinik Ulm; Abteilung Gynäkologie	Ulm
Greece	Anticancer Hospital Ag. Savas ; 2Nd Dept. of Oncology - Internal Medicine	Athens
Greece	Univ General Hosp Heraklion; Medical Oncology	Heraklion
Greece	Euromedical General Clinic of Thessaloniki; Oncology Department	Thessaloniki
Hong Kong	Queen Mary Hospital; Dept of Medicine	Hong Kong
Hong Kong	Prince of Wales Hospital; Department of Clinical Onocology	Shatin
Hungary	Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly	Budapest
Hungary	Uzsoki Utcai Korhaz; Onkoradiológiai Osztály	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont ; Department of Oncology	Debrecen
Hungary	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet; Megyei Onkologiai Kozpont	Szolnok
Italy	Irccs Centro Di Riferimento Oncologico (CRO)	Aviano	Friuli-Venezia Giulia
Italy	Ospedale Santa Maria Annunziata; Oncologia	Bagno a Ripoli	Toscana
Italy	Az. Osp. Spedali Civili; Divisione Di Oncologia - Iii Medicina	Brescia	Lombardia
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	Lombardia
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli	Campania
Italy	IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II	Padova	Veneto
Italy	A.O. Universitaria Di Parma	Parma	Emilia-Romagna
Italy	Azienda Ospedaliero Universitaria Pisana; Unita Operativa Oncologia Medica 2	Pisa	Toscana
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Kyungpook National University Medical Center	Daegu
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Ewha Womans University Mokdong Hospital	Seoul
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Malaysia	Hospital Sultan Ismail; Oncology	Johor Bahru	Johor
Malaysia	National Cancer Institute IKN	Putrajaya	Federal Territory OF Putrajaya
Malaysia	Sarawak General Hospital; Department of Radiotherapy, Oncology and Palliative care	Sarawak
New Zealand	Palmerston North Hospital; Regional Cancer Treatment Service	Palmerston North
Poland	Centrum Terapii Wspolczesnej J.M.Jasnorzewska Spolka Komandytowo-Akcyjna	?ód?
Poland	Narodowy Instytut Onkologii Odzia? w Gliwicach; Centrum Diagnostyki i Leczenia Chorób Piersi	Gliwice
Poland	Przychodnia Lekarska KOMED, Roman Karaszewski	Konin
Poland	Opolskie Centrum Onkologii; Onkologia Kliniczna z Odcinkiem Dziennym	Opole
Poland	Lecznice Citomed Sp. z o.o.	Torun
Poland	Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowtw.Piersi i Chir.Rekonstr	Warszawa
Poland	Wojskowy Instytut Medyczny; Klinika Onkologii	Warszawa
Portugal	Centro Clinico Champalimaud; Oncologia Medica	Lisboa
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Russian Federation	Blokhin Cancer Research Center; Out-Patients Dept	Moscow	Moskovskaja Oblast
Russian Federation	MEDSI Clinical Hospital on Pyatnitsky Highway; Department of antitumor drug therapy	Moscow	Moskovskaja Oblast
Russian Federation	Moscow Clinical Scientific Center	Moscow	Moskovskaja Oblast
Russian Federation	LLC Medscan	Moskva	Moskovskaja Oblast
Russian Federation	Medical Clinic "AB Medical group"	Sankt-peterburg	Sankt Petersburg
Russian Federation	Volgograd Regional Clinical Oncology Dispensary	Volgograd
Russian Federation	Regional Clinical Oncology Hospital	Yaroslavl
Russian Federation	Clinical Hospital Lapino (LLC Haven)	Yudino	Moskovskaja Oblast
Singapore	National Cancer Centre; Medical Oncology	Singapore
Singapore	National University Hospital; National University Cancer Institute, Singapore (NCIS)	Singapore
Spain	Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia	Badalona	Barcelona
Spain	Hospital Clinic de Barcelona. Unidad de Nuevas Terapias;Oncology Department	Barcelona
Spain	Hospital del Mar; Servicio de Oncologia	Barcelona
Spain	Insituto Catalán de Oncologia (ICO)	Barcelona
Spain	Vall d?Hebron Institute of Oncology (VHIO), Barcelona	Barcelona
Spain	Hospital General Universitario de Elche; Servicio de Oncologia	Elche	Alicante
Spain	Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia	Jaen
Spain	Hospital Universitario de Canarias;servicio de Oncologia	La Laguna	Tenerife
Spain	Clinica Universidad de Navarra-Madrid	Madrid
Spain	Hospital Clinico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Universitario Puerta de Hierro; Servicio de Oncologia	Majadahonda	Madrid
Spain	Clinica Universitaria de Navarra; Servicio de Oncologia	Pamplona	Navarra
Spain	Hospital Universitario Virgen Macarena; Servicio de Oncologia	Sevilla
Spain	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia
Spain	Instituto Valenciano Oncologia; Oncologia Medica	Valencia
Taiwan	Kaohsiung Medical Uni Chung-Ho Hospital; Dept of Surgery	Kaohsiung
Taiwan	Chi-Mei Medical Centre; Hematology & Oncology	Tainan
Taiwan	National Taiwan Uni Hospital; General Surgery	Taipei
Taiwan	Tri-Service General Hospital, Division of General Surgery	Taipei
Taiwan	VETERANS GENERAL HOSPITAL; Department of General Surgery	Taipei
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology	Taipei City
Thailand	Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital; Department of Surgery/Head Neck and Breast Unit; Clinical Trial	Chiang Mai
Thailand	Chulabhorn Hospital; Medical Oncology	Lak Si
Thailand	Songklanagarind Hospital; Department of Oncology	Songkhla
Turkey	Adana Baskent University Hospital; Medical Oncology	Adana
Turkey	Gulhane Training and Research Hospital	Ankara
Turkey	Ege University Medical Faculty; Medical Oncology Department	Bornova, ?zm?r
Turkey	Istanbul University Cerrahpasa Faculty of Medicine	Istanbul
Turkey	Prof. Dr. Cemil Tascioglu City Hospital; Med Onc	Istanbul
Ukraine	City Clinical Hospital #4	Dnipropetrovsk
Ukraine	Municipal Institution SubCarpathian Clinical Oncological Centre; Surgical department#2	Ivano-Frankivsk	KIEV Governorate
Ukraine	SI Institute of general&urgent surgery n/a Zaytseva V.T NAMSU; Purulent Surgery department	Kharkiv	Kharkiv Governorate
Ukraine	ME Kryviy Rih Oncology Dispensary of Dnipropetrovs?k Regional Council; Chemotherapy Department	Kryvyi Rih
Ukraine	Kyiv City Clinical Oncological Center	Kyiv
Ukraine	RCI Sumy Regional Clinical Oncological Dispensary	Sumy
Ukraine	Uzhhorod Central City Clinical Hospital	Uzhhorod	KIEV Governorate
United Kingdom	Bristol Royal Infirmary	Bristol
United Kingdom	Princess Alexandra Hospital; Oncology Department	Harlow
United Kingdom	Barts Health NHS Trust; Cancer Research Delivery Group	London
United Kingdom	Royal Marsden Hospital - Fulham; Oncology Department	London
United Kingdom	St Georges University Hospitals NHS Foundation Trust	London
United Kingdom	Christie Foundation Trust	Manchester
United Kingdom	Mount Vernon Hospital; Mount Vernon Cancer Centre	Northwood
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	Churchill Hospital; Department of Oncology	Oxford
United Kingdom	Peterborough City Hospital, Edith Cavell Campus; Oncology Department	Peterborough
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital	Portsmouth
United Kingdom	Royal Marsden Hosp NHS Fnd; Medicine - Breast Unit	Sutton
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Texas Onc-Central Austin CA Ct	Austin	Texas
United States	Beverly Hills Cancer Center	Beverly Hills	California
United States	Massachusetts General Hospital.	Boston	Massachusetts
United States	Sarah Cannon Research Institute / Tennessee Oncology	Chattanooga	Tennessee
United States	Texas Tech University Health Sciences Center; Department of Internal Medicine	El Paso	Texas
United States	Tennessee Oncology - Nashville	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Florida Cancer Specialists (St. Petersburg ? St. Anthony?s Professional Building)	Saint Petersburg	Florida
United States	Northwest Medical Specialties	Tacoma	Washington
United States	Texas Oncology - Northeast Texas	Tyler	Texas
United States	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Denmark,  France,  Georgia,  Germany,  Greece,  Hong Kong,  Hungary,  Italy,  Korea, Republic of,  Malaysia,  New Zealand,  Poland,  Portugal,  Russian Federation,  Singapore,  Spain,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)		From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 6 years)
Secondary	Objective Response Rate (ORR)		Up to 6 years
Secondary	Best Overall Response Rate (BOR)		Up to 6 years
Secondary	Duration of Response (DOR)		From the first occurrence of a CR or PR to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 6 years)
Secondary	Clinical Benefit Rate (CBR)		Up to 6 years
Secondary	Overall Survival (OS)		From randomization to death from any cause (up to 6 years)
Secondary	Time to Deterioration (TTD) in Pain		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)
Secondary	TTD in Physical Function		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)
Secondary	TTD in Role Function		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)
Secondary	TTD in Global Health Status		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)
Secondary	Percentage of Participants with Adverse Events		From randomization through the end of study (up to 6 years)
Secondary	Plasma Concentration of Inavolisib		At pre-defined intervals from baseline to the end of study (up to 6 years)
Secondary	Plasma Concentration of Palbociclib		At pre-defined intervals from baseline to the end of study (up to 6 years)
Secondary	Plasma Concentration of Fulvestrant		At pre-defined intervals from baseline to the end of study (up to 6 years)