A Study of Ipatasertib in Combination With Paclitaxel as a Treatment for Participants With PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple-Negative Breast Cancer or Hormone Receptor-Positive, HER2-Negative Breast Cancer

NCT ID: NCT03337724

Last Updated: 2024-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 579 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-06
• Study Completion Date: 2023-01-04

Brief Summary

This study will evaluate the efficacy of ipatasertib + paclitaxel versus placebo + paclitaxel in participants with histologically confirmed, locally advanced or metastatic triple-negative breast cancer (TNBC) and in participants with locally advanced or metastatic hormone receptor positive (HR+)/ human epidermal growth factor receptor 2 negative (HER2-) breast adenocarcinoma who are not suitable for endocrine therapy.

Conditions

Breast Cancer

Study Design

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

Study Groups

Ipatasertib + Paclitaxel

Group Type: EXPERIMENTAL

Ipatasertib

Intervention Type: DRUG

Ipatasertib, 400 milligrams (mg), administered orally once a day (QD) on Days 1-21 of each 28-day cycle until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Paclitaxel

Intervention Type: DRUG

Paclitaxel, 80 mg/square meter (m\^2), administered intravenously (IV) on Days 1, 8, and 15 of each 28-day cycle until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Placebo + Paclitaxel

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

Paclitaxel, 80 mg/square meter (m\^2), administered intravenously (IV) on Days 1, 8, and 15 of each 28-day cycle until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Placebo

Intervention Type: DRUG

Matching placebo, administered orally QD on Days 1-21 of each 28-day cycle until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Interventions

Ipatasertib

Ipatasertib, 400 milligrams (mg), administered orally once a day (QD) on Days 1-21 of each 28-day cycle until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Intervention Type: DRUG

Paclitaxel

Paclitaxel, 80 mg/square meter (m\^2), administered intravenously (IV) on Days 1, 8, and 15 of each 28-day cycle until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Intervention Type: DRUG

Placebo

Matching placebo, administered orally QD on Days 1-21 of each 28-day cycle until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Women or men aged =>18 years with histologically documented triple-negative breast cancer (TNBC) or HR+/HER2- adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to resection with curative intent
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Adequate hematologic and organ function within 14 days prior to treatment initiation
• Histologically documented TNBC or HR+/HER2- adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to resection with curative intent
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Eligible for taxane monotherapy, as per local investigator assessment (e.g., absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control which may require combination chemotherapy)
• HR+/HER2- breast cancer that is not considered appropriate for endocrine-based therapy and meets one of the following: patient has recurrent disease <=5 years of being on adjuvant endocrine therapy or if patient with de novo metastatic disease have progressed within 6 months of being on first line endocrine therapy.
• Consent to submit a formalin-fixed, paraffin-embedded tumor (FFPE) tissue block or freshly cut unstained, serial tumor slides from the most recently collected tumor tissue for central molecular analysis
• Confirmation of biomarker eligibility using an appropriately validated molecular assay at a diagnostic laboratory, Clinically Laboratory Improvement Amendments (CLIA) or equivalently accredited i.e., valid results from either central testing or local testing of tumor tissue or blood demonstrating PIK3CA/AKT1/PTEN-altered status
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods and agreement to refrain from donating sperm

Exclusion Criteria

• Treatment with approved or investigational cancer therapy within 14 days prior to treatment initiation
• Any previous chemotherapy for inoperable locally advanced or metastatic TNBC or HR+/HER2- adenocarcinoma of the breast (patients receiving neo/adjuvant chemotherapy eligible provided they have at least a 12 month disease-free interval)
• History of or known presence of brain or spinal cord metastases
• Malignancies other than breast cancer within 5 years prior to treatment initiation (except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer)
• Prior treatment with an Akt inhibitor (prior PI3K or mTOR inhibitors are allowed)
• History of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills
• Active infection requiring systemic anti-microbial treatment (including antibiotics, anti-fungals, and anti-viral agents)
• Known human immunodeficiency virus (HIV) infection
• Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis, current drug or alcohol abuse, or cirrhosis
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of treatment (or anticipated need during study)
• Pregnant or breastfeeding, or intending to become pregnant during the study
• Clinically significant cardiac dysfunction (including NYHA Class II/III/IV heart failure, left ventricular ejection fraction [LVEF] <50%, active ventricular arrhythmia requiring medication, history of myocardial infarction within 6 months of treatment initiation, clinically significant electrocardiogram [ECG] abnormalities).
• Need for chronic corticosteroid therapy of >=10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressants for a chronic disease
• Unresolved, clinically significant toxicity from prior therapy, except for alopecia and Grade 1 peripheral neuropathy
• Uncontrolled clinical symptoms including pleural effusion, pericardial effusion, or ascites, tumor-related pain, hypercalcemia (or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy)
• History of Type I or Type II diabetes mellitus requiring insulin
• Grade >=2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia
• History of or active inflammatory bowel disease or active bowel inflammation
• Clinically significant lung disease (including pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, active infection/ history of opportunistic infections)
• Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of treatment
• Grade >=2 peripheral neuropathy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• 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

UCSD Moores Cancer Center

La Jolla, California, United States

USC Norris Cancer Center

Los Angeles, California, United States

USC Norris Cancer Center; USC Oncology Hematology Newport Beach

Newport Beach, California, United States

Kaiser Permanente - Oakland

Oakland, California, United States

Kaiser Permanente - Roseville

Roseville, California, United States

UC Davis; Comprehensive Cancer Center

Sacramento, California, United States

Kaiser Permanente Sacramento Medical Center

Sacramento, California, United States

Kaiser Permanente - San Francisco (2238 Geary)

San Francisco, California, United States

UCSF Comprehensive Cancer Ctr

San Francisco, California, United States

K. Permanente - San Jose

San Jose, California, United States

Kaiser Permanente - San Leandro

San Leandro, California, United States

K. Permanente - Santa Clara

Santa Clara, California, United States

Kaiser Permanente - South San Francisco

South San Francisco, California, United States

Kaiser Permanente - Vallejo

Vallejo, California, United States

K. Permanente - Walnut Creek

Walnut Creek, California, United States

Memorial Regional Hospital

Hollywood, Florida, United States

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, United States

UF Health Cancer Center at Orlando Health

Orlando, Florida, United States

Memorial Hospital West

Pembroke Pines, Florida, United States

University of Maryland

Baltimore, Maryland, United States

Mercy Medical Center

Baltimore, Maryland, United States

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Memorial Sloan Kettering Cancer Center at Westchester

Harrison, New York, United States

Memorial Sloan Kettering

New York, New York, United States

West Clinic

Germantown, Tennessee, United States

Texas Oncology, P.A.

Dallas, Texas, United States

UT Southwestern Medical Center; Simmons Comprehensive Cancer Center, Simmons Pharmacy

Dallas, Texas, United States

Oncology Consultants PA

Houston, Texas, United States

Fundación CENIT para la Investigación en Neurociencias

Buenos Aires, , Argentina

Hosp Provincial D. Centenarios; Oncology Dept

Rosario, , Argentina

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

Calvary Mater Newcastle; Medical Oncology

Waratah, New South Wales, Australia

Westmead Hospital; Medical Oncology

Wentworthville, New South Wales, Australia

Mater Hospital; Cancer Services

South Brisbane, Queensland, Australia

Cabrini Medical Centre; Oncology

Malvern, Victoria, Australia

Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit

Bull Creek, Western Australia, Australia

Cliniques Universitaires St-Luc

Brussels, , Belgium

GHdC Site Notre Dame

Charleroi, , Belgium

UZ Leuven Gasthuisberg

Leuven, , Belgium

Santa Casa de Misericordia de Salvador

Salvador, Estado de Bahia, Brazil

Hospital Araujo Jorge; Departamento de Ginecologia E Mama

Goiânia, Goiás, Brazil

Hospital do Câncer de Londrina

Londrina, Paraná, Brazil

Instituto Nacional de Cancer - INCa; Oncologia

Rio de Janeiro, Rio de Janeiro, Brazil

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Nossa Senhora da Conceicao

Porto Alegre, Rio Grande do Sul, Brazil

Faculdade de Medicina do ABC - FMABC

Santo André, São Paulo, Brazil

Hospital Perola Byington

São Paulo, São Paulo, Brazil

British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

Jewish General Hospital

Montreal, Quebec, Canada

Sociedad de Investigaciones Medicas Ltda (SIM)

Temuco, , Chile

Clinica CIMCA

San José, , Costa Rica

ICIMED Instituto de Investigación en Ciencias Médicas

San José, , Costa Rica

Masaryk?v onkologický ústav; Klinika komplexní onkologické pé?e

Brno, , Czechia

Fakultni nemocnice Olomouc; Onkologicka klinika

Olomouc, , Czechia

CHU Besançon - Hôpital Jean Minjoz

Besançon, , France

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, , France

Centre Georges Francois Leclerc; Oncologie 3

Dijon, , France

ICM; Medecine B3

Montpellier, , France

Centre Catherine De Sienne

Nantes, , France

APHP - Hospital Saint Louis

Paris, , France

Institut Jean Godinot; Oncologie Medicale

Reims, , France

Onkologische Schwerpunktpraxis Kurfürstendamm

Berlin, , Germany

Praxis Dr.med. Katja Ziegler-Löhr

Cologne, , Germany

Praxis für Interdisziplinäre Onkologie und Hämatologie GbR

Freiburg im Breisgau, , Germany

Universitätsklinikum Hamburg-Eppendorf; Frauenklinik

Hamburg, , Germany

Universitätsklinikum des Saarlandes; Klinik f. Frauenheilkunden und Geburtshilfe

Homburg/Saar, , Germany

Dres. Andreas Köhler und Roswitha Fuchs

Langen, , Germany

Mühlenkreiskliniken; Johannes Wesling Klinikum Minden; Klinik für Frauenheilkunde und Geburtshilfe

Minden, , Germany

Oncologianova GmbH - Gesellschaft für Innovationen in der Onkologie

Recklinghausen, , Germany

Universitätsfrauen- und Poliklinik am Klinikum Suedstadt

Rostock, , Germany

Universitätsklinikum Würzburg; Frauenklinik

Würzburg, , Germany

Anticancer Hospital Ag Savas; 1St Dept of Internal Medicine

Athens, , Greece

Agioi Anargyroi; 3Rd Dept. of Medical Oncology

Athens, , Greece

Euromedical General Clinic of Thessaloniki; Oncology Department

Thessaloniki, , Greece

Orszagos Onkologial Intezet; Onkologiai Osztaly X

Budapest, , Hungary

Borsod-Abauj-Zemplen Megyei Korhaz Es Egyetemi Oktato Korhaz; Onkologiai Osztaly

Miskolc, , Hungary

Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika

Szeged, , Hungary

Hetenyi Geza County Hospital; Onkologiai Kozpont

Szolnok, , Hungary

Zala County Hospital ICU

Zalaegerszeg, , Hungary

Indraprastha Apollo Hospitals

New Delhi, National Capital Territory of Delhi, India

Rajiv Gandhi Cancer Inst.&Research Center; Medical Oncology

New Delhi, National Capital Territory of Delhi, India

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

Napoli, Campania, Italy

Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica

Bologna, Emilia-Romagna, Italy

Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica

Aviano, Friuli Venezia Giulia, Italy

Ospedale Santa Maria Annunziata; Oncologia

Bagno a Ripoli, Tuscany, Italy

IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II

Padua, Veneto, Italy

Aichi Cancer Center Hospital

Aichi, , Japan

National Cancer Center Hospital East

Chiba, , Japan

National Hospital Organization Kyushu Cancer Center;Breast Oncology

Fukuoka, , Japan

Fukushima Medical University Hospital

Fukushima, , Japan

Hyogo Medical University Hospital

Hyōgo, , Japan

St. Marianna University Hospital

Kanagawa, , Japan

Kanagawa Cancer Center

Kanagawa, , Japan

Tokai University Hospital

Kanagawa, , Japan

Kumamoto Shinto General Hospital

Kumamoto, , Japan

Niigata Cancer Center Hospital

Niigata, , Japan

Okayama University Hospital

Okayama, , Japan

National Hospital Organization Osaka National Hospital

Osaka, , Japan

Kinki University Hospital, Faculty of Medicine; Surgery

Osaka, , Japan

Saitama Cancer Center, Breast Oncology

Saitama, , Japan

Shizuoka Cancer Center

Shizuoka, , Japan

National Cancer Center Hospital

Tokyo, , Japan

St. Luke's International Hospital

Tokyo, , Japan

The Cancer Institute Hospital of JFCR

Tokyo, , Japan

Showa University Hospital; Breast Surgery

Tokyo, , Japan

Centro Medico Dalinde

Mexico City, Mexico CITY (federal District), Mexico

Centro Médico Zambrano Hellion

Monterrey, Nuevo León, Mexico

Merida | Investigacion Clinica

Mérida, Yucatán, Mexico

CENEIT Oncologicos; DENTRO DE CONDOMINIO SAN FRANCISCO

Mexico City, , Mexico

Clinical Hospital; Oncology Department

Bitola, , North Macedonia

PHI University Clinic of Radiotherapy and Oncology; Breast malignancy

Skopje, , North Macedonia

PHI University Clinic of Radiotherapy and Oncology; Malignant diseases of thorax

Skopje, , North Macedonia

Centro Medico Monte Carmelo

Arequipa, , Peru

Hospital Daniel Alcides Carrion

Callao, , Peru

Clínica San Gabriel; Unidad de Investigación Oncológica de la Clínica San Gabriel

Lima, , Peru

Hospital Nacional Cayetano Heredia; Ocología; Servicio de Hematología Oncología Médica

Lima, , Peru

Oncosalud Sac; Oncología

Lima, , Peru

Instituto Nacional de Enfermedades Neoplasicas

Lima, , Peru

Clinica Ricardo Palma

San Isidro, , Peru

Instituto Regional de Enfermedades Neoplasicas - IREN Norte

Trujillo, , Peru

Instyt. Centrum Zdrowia Matki Polki; Klinika Chirurgii Onk. Chorób Piersi z Podod. Onko Klinicznej

?ód?, , Poland

Narodowy Inst.Onkol.im.Sklodowskiej-Curie Panstw.Inst.Bad Gliwice; III Klin. Radioter. i Chemioter.

Gliwice, , Poland

Narodowy Instytut Onkologii im. M.Sklodowskiej-Curie; Klinika Nowotworow Piersi i Chirurgii Rekonstr

Warsaw, , Poland

Arkhangelsk Regional Clinical Oncology Dispensary

Arkhangelsk, Arhangelsk, Russia

Moscow City Oncology Hospital #62

Moscovskaya Oblast, Moscow Oblast, Russia

Federal State Institution, Moscow Research Oncology Institute n.a. P.A. Hertzen; Oncourology

Moscow, Moscow Oblast, Russia

Blokhin Cancer Research Center; Combined Treatment

Moskva, Moscow Oblast, Russia

FSI Rostov research oncological institute of MoH and SD of RF; PAD

Rostov-on-Don, Rostov Oblast, Russia

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

Saint Petersburg, Sankt-Peterburg, Russia

Clinical Oncology Dispensary of Ministry of Health of Tatarstan

Kazan', Tatarstan Republic, Russia

Ivanovo Regional Oncology Dispensary

Ivanovo, , Russia

SBIH Kaluga Region Clinical Oncology Dispensary

Kaluga, , Russia

National University Hospital; National University Cancer Institute, Singapore (NCIS)

Singapore, , Singapore

National Cancer Centre; Medical Oncology

Singapore, , Singapore

Institute of Oncology Ljubljana

Ljubljana, , Slovenia

Medical Oncology Centre of Rosebank; Oncology

Johannesburg, , South Africa

National Cancer Center

Goyang-si, , South Korea

Inha University Hospital

Incheon, , South Korea

Seoul National University Bundang Hospital

Seongnam-si, , 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

Hospital Provincial de Castellon; Servicio de Oncologia

Castellon, Castellon, Spain

Hospital Universitario Reina Sofia; Servicio de Oncologia

Córdoba, Cordoba, Spain

Hospital de Donostia; Servicio de Oncologia

Guipuzcoa, Guipuzcoa, Spain

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 del Mar; Servicio de Oncologia

Barcelona, , Spain

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, , Spain

Hospital Clinic Barcelona; Servicio de oncologia

Barcelona, , 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

Hospital Universitario Virgen del Rocio; Servicio de Oncologia

Seville, , Spain

Hospital Clinico Universitario; Oncologia

Valencia, , Spain

Chi Mei Medical Center Liou Ying Campus

Liuying Township, , Taiwan

VETERANS GENERAL HOSPITAL; Department of General Surgery

Taipei, , Taiwan

National Taiwan Uni Hospital; General Surgery

Taipei, , Taiwan

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

Taipei, , Taiwan

Ankara Bilkent City Hospital

Ankara, , Turkey (Türkiye)

Dicle Uni Medical Faculty; Internal Medicine

Diyarbakır, , Turkey (Türkiye)

Medipol University Medical Faculty; Oncology Department

Istanbul, , Turkey (Türkiye)

Prof. Dr. Cemil Tascioglu City Hospital; Med Onc

Istanbul, , Turkey (Türkiye)

Katip Celebi University Ataturk Training and Research Hospital; Oncology

Izmir, , Turkey (Türkiye)

Sakarya University Medical School; Medical Oncology

Sakarya, , Turkey (Türkiye)

Chemotherapy SI Dnipropetrovsk MA of MOHU

Dnipropetrovsk, , Ukraine

Kyiv City Clinical Oncological Center, Day Hospital Department for Oncological patients

Kiev, , Ukraine

National Cancer Institute MOH of Ukraine

Kiev, , Ukraine

Lviv State Oncological Regional Treatment and Diagnostic Center

Lviv, , Ukraine

Velindre Cancer Centre

Cardiff, , United Kingdom

University Hospital coventry; Oncology Department

Coventry, , United Kingdom

The Beatson West of Scotland Cancer Centre; Cancer Clinical Trials Unit

Glasgow, , United Kingdom

Royal Marsden Hospital - London

London, , United Kingdom

Derriford Hospital

Plymouth, , United Kingdom

Royal Stoke University Hospital

Stoke-on-Trent, , United Kingdom

Royal Marsden Hospital; Dept of Medical Oncology

Sutton, , United Kingdom

Countries

United States; Argentina; Australia; Belgium; Brazil; Canada; Chile; Costa Rica; Czechia; France; Germany; Greece; Hungary; India; Italy; Japan; Mexico; North Macedonia; Peru; Poland; Russia; Singapore; Slovenia; South Africa; South Korea; Spain; Taiwan; Turkey (Türkiye); Ukraine; United Kingdom

References

Turner N, Dent RA, O'Shaughnessy J, Kim SB, Isakoff SJ, Barrios C, Saji S, Bondarenko I, Nowecki Z, Lian Q, Reilly SJ, Hinton H, Wongchenko MJ, Kovic B, Mani A, Oliveira M. Ipatasertib plus paclitaxel for PIK3CA/AKT1/PTEN-altered hormone receptor-positive HER2-negative advanced breast cancer: primary results from cohort B of the IPATunity130 randomized phase 3 trial. Breast Cancer Res Treat. 2022 Feb;191(3):565-576. doi: 10.1007/s10549-021-06450-x. Epub 2021 Dec 3.

Reference Type: DERIVED

PMID: 34860318 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-001548-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CO40016

Identifier Type: -

Identifier Source: org_study_id