A Study of Taselisib + Fulvestrant Versus Placebo + Fulvestrant in Participants With Advanced or Metastatic Breast Cancer Who Have Disease Recurrence or Progression During or After Aromatase Inhibitor Therapy

NCT ID: NCT02340221

Last Updated: 2022-07-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 631 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-09
• Study Completion Date: 2021-06-29

Brief Summary

This international, multicenter, randomized, double-blinded, placebo-controlled study is designed to compare the efficacy and safety of taselisib + fulvestrant with that of placebo + fulvestrant in postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative, oncogene that encodes for phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA)-mutant, unresectable, locally advanced or metastatic breast cancer after recurrence or progression during or after an aromatase inhibitor (AI) therapy. There will be a 2:1 randomization to the taselisib arm versus the placebo arm. Enrollment will be enriched for participants with PIK3CA mutant tumors via central testing. The anticipated duration of the study is approximately 3.5 years.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Taselisib + Fulvestrant

Participants received taselisib 4 milligrams (mg) taken orally QD beginning at Cycle 1, Day 1 and fulvestrant 500 mg by IM injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.

Group Type: EXPERIMENTAL

Taselisib

Intervention Type: DRUG

Taselisib 4 mg was administered as two tablets of 2 mg each as per the schedule specified in the respective arm.

Fulvestrant

Intervention Type: DRUG

Fulvestrant 500 mg was administered as two IM injections of 250 mg each as per the schedule specified in the respective arms.

Placebo + Fulvestrant

Participants received placebo taken orally once daily (QD) beginning at Cycle 1, Day 1, and fulvestrant 500 mg administered by intramuscular (IM) injection at Cycle 1, Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until disease progression, unacceptable toxicity, or study termination by the Sponsor.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo matching to taselisib was administered as per the schedule specified in the respective arm.

Fulvestrant

Intervention Type: DRUG

Fulvestrant 500 mg was administered as two IM injections of 250 mg each as per the schedule specified in the respective arms.

Interventions

Taselisib

Taselisib 4 mg was administered as two tablets of 2 mg each as per the schedule specified in the respective arm.

Intervention Type: DRUG

Placebo

Placebo matching to taselisib was administered as per the schedule specified in the respective arm.

Intervention Type: DRUG

Fulvestrant

Fulvestrant 500 mg was administered as two IM injections of 250 mg each as per the schedule specified in the respective arms.

Intervention Type: DRUG

Other Intervention Names

GDC-0032, RO5537381; Faslodex

Eligibility Criteria

Inclusion Criteria

• Postmenopausal women with histologically or cytologically confirmed locally advanced or metastatic estrogen receptor (ER) positive breast cancer
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Participants for whom endocrine therapy (example [e.g.], fulvestrant) is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study
• Radiologic/objective evidence of recurrence or progression to the most recent systemic therapy for breast cancer
• Radiologic/objective evidence of breast cancer recurrence or progression while on or within 12 months of the end of adjuvant treatment with an aromatase inhibitor (AI), or progression while on or within 1 month of the end of prior AI treatment for locally advanced or metastatic breast cancer
• Measurable disease via Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) or non-measurable, evaluable disease with at least one evaluable bone lesion via RECIST v1.1
• Consent to provide a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block (preferred) or a minimum of 20 (25 preferred) freshly cut unstained tumor slides from the most recently collected, available tumor tissue for oncogene that encodes for phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA)-mutation testing
• A valid cobas PIK3CA mutation result by central testing is required
• Adequate hematologic and end-organ function within 28 days prior to treatment initiation

Exclusion Criteria

• Human epidermal growth factor receptor 2 (HER2)-positive disease by local laboratory testing (immunohistochemistry 3 positive [IHC 3+] staining or in situ hybridization positive)
• Prior treatment with fulvestrant
• Prior treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor, mammalian target of rapamycin (mTOR) inhibitor (e.g. everolimus), or protein kinase B (AKT) inhibitor
• Prior anti-cancer therapy within 2 weeks prior to Day 1 of Cycle 1
• Prior radiation therapy within 2 weeks prior to Day 1 of Cycle 1
• All acute treatment-related toxicity must have resolved to Grade less than or equal to (</=) 1 or be deemed stable by the Investigator
• Prior treatment with greater than (>) 1 cytotoxic chemotherapy regimen for metastatic breast cancer
• Concurrent hormone replacement therapy
• Known untreated or active central nervous system (CNS) metastases
• Type 1 or Type 2 diabetes mellitus requiring anti-hyperglycemic medications
• History of inflammatory bowel disease or active bowel inflammation
• Clinically significant cardiac or pulmonary dysfunction
• Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with human immunodeficiency virus (HIV), hepatitis B or C virus

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Arizona Oncology

Tucson, Arizona, United States

Arizona Oncology Associates, P.C.

Tucson, Arizona, United States

Georgia Cancer Specialists - Northside

Atlanta, Georgia, United States

Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital

Marietta, Georgia, United States

Ingalls Hospital

Harvey, Illinois, United States

Maryland Oncology Hematology

Rochville, Maryland, United States

Dana Farber Can Ins

Boston, Massachusetts, United States

Mercy Hospitals East Communities d/b/a Mercy Hospital St. Louis

St Louis, Missouri, United States

MSKCC at Basking Ridge

Basking Ridge, New Jersey, United States

John Theurer Cancer Ctr at Hackensack Univ Medical Ctr

Hackensack, New Jersey, United States

Memorial Sloan-Kettering; Cancer Center

Commack, New York, United States

Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering; at Westchester

Harrison, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Memorial Sloan Kettering Nassau

Uniondale, New York, United States

Oregon Health & Science University; Knight Cancer Institute, Community Hematology Oncology

Beaverton, Oregon, United States

Pinnacle Health

Harrisburg, Pennsylvania, United States

Liverpool Hospital; Cancer Therapy Centre

Liverpool, New South Wales, Australia

Macquarie University Hospital

Macquarie Park, New South Wales, Australia

Newcastle Mater Misericordiae Hospital; Oncology

Waratah, New South Wales, Australia

Mater Hospital; Oncology

Brisbane, Queensland, Australia

Austin Hospital; Medical Oncology

Heidelberg, Victoria, Australia

Sunshine Hospital; Oncology Research

St Albans, Victoria, Australia

St John of God Murdoch Hospital; Oncology West

Murdoch, Western Australia, Australia

Lkh-Univ. Klinikum Graz; Klinik Für Innere Medizin I

Graz, , Austria

Tiroler Landeskrankenanstalten Ges.M.B.H.; Abt. Für Gynäkologie

Innsbruck, , Austria

Ordensklinikum Linz Barmherzige Schwestern; Abt. fur Innere Medizin 1

Linz, , Austria

Medizinische Universität Wien; Univ.Klinik für Innere Medizin I

Vienna, , Austria

University Clinical Center of the Republic of Srpska

Banja Luka, , Bosnia and Herzegovina

Clinic of Oncology, University Clinical Center Sarajevo

Sarajevo, , Bosnia and Herzegovina

Complex Oncological Center - Plovdiv, EOOD

Plovdiv, , Bulgaria

MHAT Nadezhda

Sofia, , Bulgaria

SHATO - Sofia

Sofia, , Bulgaria

SHATOD Dr. Marko Antonov Markov-Varna, EOOD

Varna, , Bulgaria

Cross Cancer Institute

Edmonton, Alberta, Canada

British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

Grand River Hospital

Kitchener, Ontario, Canada

The Ottawa Hospital Cancer Centre; Oncology

Ottawa, Ontario, Canada

Sunnybrook Health Science Centre

Toronto, Ontario, Canada

McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology

Montreal, Quebec, Canada

Hospital Du Saint-Sacrement

Québec, Quebec, Canada

the First Hospital of Jilin University

Changchun, , China

Jilin Cancer Hospital

Changchun, , China

Jiangsu Cancer Hospital

Nanjing, , China

Fudan University Shanghai Cancer Center

Shanghai, , China

Zhejiang Cancer Hospital

Zhejiang, , China

Clinica del Country

Bogotá, , Colombia

Oncomedica S.A.

Montería, , Colombia

University Hospital; Oncology and Radiotherapy

Hradec Králové, , Czechia

Fakultni nemocnice Olomouc; Onkologicka klinika

Olomouc, , Czechia

Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

KYS Sadesairaala; Syopatautien poliklinikka

Kuopio, , Finland

Turku Uni Central Hospital; Oncology Clinics

Turku, , Finland

Centre Jean Perrin; Hopital De Semaine

Clermont-Ferrand, , France

Centre Georges François Leclerc; Service Pharmacie, Bp 77980

Dijon, , France

Hopital Prive Drome Ardeche; Chir 2A 2B

Guilherand-Granges, , France

CHD Vendée

La Roche-sur-Yon, , France

Hopital Dupuytren; Oncologie Medicale

Limoges, , France

Institut régional du Cancer Montpellier

Montpellier, , France

Institut Curie; Oncologie Medicale

Paris, , France

Ch Lyon Sud; Onco Secteur Jules Courmont

Pierre-Bénite, , France

Pole de Cancerologie Prive Strasbourgeois

Strasbourg, , France

Centre Alexis Vautrin; Oncologie Medicale

Vandœuvre-lès-Nancy, , France

Hochwaldkrankenhaus; Abt.Gynäkologie Geburtshilfe u.Senologie

Bad Nauheim, , Germany

Praxisklinik Krebsheilkunde für Frauen / Brustzentrum (Dres. Kittel/Klare)

Berlin, , Germany

Onkologische Schwerpunktpraxis Kurfürstendamm

Berlin, , Germany

Universitätsklinikum Essen; Zentrum Für Frauenheilkunde

Essen, , Germany

Kooperatives Mammazentrum Hamburg Krankenhaus Jerusalem

Hamburg, , Germany

Klinikum der Universität München; Frauenklinik - Onkologie II

München, , Germany

Klinikum Mutterhaus der Borromäerinnen, Innere Medizin I

Trier, , Germany

Alexandras General Hospital of Athens; Oncology Department

Athens, , Greece

IASO General Hospital of Athens

Athens, , Greece

Univ General Hosp Heraklion; Medical Oncology

Heraklion, , Greece

University Hospital of Patras Medical Oncology

Pátrai, , Greece

Euromedical General Clinic of Thessaloniki; Oncology Department

Thessaloniki, , Greece

Papageorgiou General Hospital; Medical Oncology

Thessaloniki, , Greece

Istituto Nazionale Tumori Irccs Fondazione g. PASCALE;U.O.C. Oncologia Medica Senologica

Napoli, Campania, Italy

ARCISPEDALE S. MARIA NUOVA - REGGIO EMILIA; Struttura Semplice Coordinamento Breast Unit Integrata

Reggio Emilia, Emilia-Romagna, Italy

A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia

Udine, Friuli Venezia Giulia, Italy

IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A

Genoa, Liguria, Italy

Istituto Europeo Di Oncologia

Milan, Lombardy, Italy

Centro Catanese Di Oncologia; Oncologia Medica

Catania, Sicily, Italy

Azienda Ospedaliero-Universitaria Careggi; SOD Radioterapia

Florence, Tuscany, Italy

Azienda USL 9 Grosseto; Dipartimento Politiche del Farmaco

Grosseto, Tuscany, Italy

Azienda usl 5 Di Pisa-Ospedale Di Pontedera;U.O. Oncologia

Pontedera, Tuscany, Italy

AZ. Usll12 Veneziana-Ospedale Dell'angelo;Oncologia Medica

Mestre, Veneto, Italy

Iem-Fucam

D.F., , Mexico

Instituto Nacional De Cancerologia; Oncology; Tumores Mamarios

Distrito Federal, , Mexico

Consultorio de Medicina Especializada; Dentro de Condominio San Francisco

Mexico City, , Mexico

Hospital San Jose Del Tec. de Monterrey; Oncology

Monterrey, , Mexico

Oaxaca Site Management Organization

Oaxaca City, , Mexico

Medisch Centrum Alkmaar

Alkmaar, , Netherlands

Ziekenhuis Rijnstate

Arnhem, , Netherlands

Instituto Nacional de Enfermedades Neoplasicas

Lima, , Peru

Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional

Lima, , Peru

Oncocenter Peru S.A.C.; Oncosalud

Lima, , Peru

Instituto Regional de Enfermedades Neoplasicas - IREN Norte

Trujillo, , Peru

Bialostockie Centrum Onkologii; Oddzial Onkologii Klinicznej

Bialystok, , Poland

Centrum Onkologii w Bydgoszczy; Oddzial Kliniczny Onkologii

Bydgoszcz, , Poland

Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii

Gdansk, , Poland

Przychodnia Lekarska KOMED, Roman Karaszewski

Konin, , Poland

Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii

Krakow, , Poland

Woj.Wielospecjalistyczne Centrum Onkologii i Traumatologii; Oddz.Hematologii Pododz.Chemioterapii

Lodz, , Poland

Centrum Onkologii Ziemi LUBELSKIEJ im. Sw Jana z Dukli, I oddz. Chemioterapii

Lublin, , Poland

Zachodniopomorskie Centrum Onkologii, Osrodek Innowacyjnosci, Rozwoju i Badan Klinicznych

Szczecin, , Poland

Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii

Warsaw, , Poland

Wojewodzki Szpital Specjalistyczny; Osrodek Badawczo-Rozwojowy, Oddzial Chemioterapii

Wroclaw, , Poland

Hospital Garcia de Orta; Servico de Oncologia Medica

Almada, , Portugal

IPO de Lisboa; Servico de Oncologia Medica

Lisbon, , Portugal

Hospital da Luz; Departamento de Oncologia Medica

Lisbon, , Portugal

Hospital de Santa Maria; Servico de Oncologia Medica

Lisbon, , Portugal

IPO do Porto; Servico de Oncologia Medica

Porto, , Portugal

Institut of Oncology Al. Trestioreanu Bucharest; Oncology Department

Bucharest, , Romania

Prof. Dr. I. Chiricuta Institute of Oncology

Cluj-Napoca, , Romania

Oncology Center Sf. Nectarie

Craiova, , Romania

Euroclinic Center of Oncology SRL

Iași, , Romania

Moscow City Oncology Hospital #62

Moscovskaya Oblast, Moscow Oblast, Russia

Regional Clinical Oncology Dispensary; Surgery Dept, Thoracic

Arkhangelsk, , Russia

Ivanovo Regional Oncology Dispensary

Ivanovo, , Russia

Clinical Oncology Dispensary of Ministry of Health of Tatarstan

Kazan', , Russia

State Inst. Of Healthcare Orenburg Regional Clinical Oncology Dis

Orenburg, , Russia

S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)

Saint Petersburg, , Russia

Institute for Onc/Rad Serbia

Belgrade, , Serbia

Inje university Haeundae Paik Hospital

Busan, , South Korea

Chungbuk National University Hospital

Cheongju-si, , South Korea

National Cancer Center

Goyang-si, , South Korea

Korea University Anam Hospital

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Ulsan University Hosiptal

Ulsan, , South Korea

Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia

Santiago de Compostela, LA Coruña, Spain

Hospital Universitario Puerta de Hierro; Servicio de Oncologia

Majadahonda, Madrid, Spain

Hospital Universitario de Canarias;servicio de Oncologia

San Cristóbal de La Laguna, Tenerife, Spain

Hospital de Cruces; Servicio de Oncologia

Bilbao, Vizcaya, Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clínic i Provincial; Servicio de Hematología y Oncología

Barcelona, , Spain

Centro Oncologico MD Anderson Internacional; Servicio de Oncologia

Madrid, , Spain

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, , Spain

HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia

Madrid, , Spain

Fundación IVO

Valencia, , Spain

Hospital Universitario Miguel Servet; Servicio Oncologia

Zaragoza, , Spain

Uni Hospital Linkoeping; Dept. of Oncology

Linköping, , Sweden

Sodersjukhuset; Onkologkliniken

Stockholm, , Sweden

Akademiska sjukhuset, Onkologkliniken

Uppsala, , Sweden

VETERANS GENERAL HOSPITAL; Department of General Surgery

Taipei, , Taiwan

National Taiwan Uni Hospital; General Surgery

Taipei, , Taiwan

Mackay Memorial Hospital; Dept of Surgery

Taipei, , Taiwan

Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology

Taipei, , Taiwan

Department of Surgery, King Chulalongkorn Memorial Hospital

Bangkok, , 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

Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology

Adana, , Turkey (Türkiye)

Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department

Edirne, , Turkey (Türkiye)

Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology

Istanbul, , Turkey (Türkiye)

Ege Uni Medical Faculty; Oncology Dept

Izmir, , Turkey (Türkiye)

Hacettepe Uni Medical Faculty Hospital; Oncology Dept

Sihhiye/Ankara, , Turkey (Türkiye)

Countries

United States; Australia; Austria; Bosnia and Herzegovina; Bulgaria; Canada; China; Colombia; Czechia; Finland; France; Germany; Greece; Italy; Mexico; Netherlands; Peru; Poland; Portugal; Romania; Russia; Serbia; South Korea; Spain; Sweden; Taiwan; Thailand; Turkey (Türkiye)

References

Moein A, Jin JY, Wright MR, Wong H. Quantitative characterization of the effects of fulvestrant alone or in combination with taselisib (PI3Kinase inhibitor) on longitudinal tumor growth in patients with estrogen receptor-positive, HER2-negative, PIK3CA-mutant, advanced or metastatic breast cancer. Cancer Chemother Pharmacol. 2024 Sep;94(3):421-436. doi: 10.1007/s00280-024-04690-4. Epub 2024 Jun 27.

Reference Type: DERIVED

PMID: 38937298 (View on PubMed)

Dent S, Cortes J, Im YH, Dieras V, Harbeck N, Krop IE, Wilson TR, Cui N, Schimmoller F, Hsu JY, He J, De Laurentiis M, Sousa S, Drullinsky P, Jacot W. Phase III randomized study of taselisib or placebo with fulvestrant in estrogen receptor-positive, PIK3CA-mutant, HER2-negative, advanced breast cancer: the SANDPIPER trial. Ann Oncol. 2021 Feb;32(2):197-207. doi: 10.1016/j.annonc.2020.10.596. Epub 2020 Nov 10.

Reference Type: DERIVED

PMID: 33186740 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2014-003185-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO29058

Identifier Type: -

Identifier Source: org_study_id