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 (IPATunity130)

February 15, 2024 updated by: Hoffmann-La Roche

A Double-Blind, Placebo-Controlled, Randomized Phase III Study of Ipatasertib in Combination With Paclitaxel as a Treatment for Patients With PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple-Negative Breast Cancer or Hormone Receptor-Positive, HER2-Negative Breast Cancer

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

579

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1125ABD
        • Fundación Cenit para la Investigación en Neurociencias
      • Rosario, Argentina, S2002KDS
        • Hosp Provincial D. Centenarios; Oncology Dept
  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Chris O'Brien Lifehouse
      • Waratah, New South Wales, Australia, 2298
        • Calvary Mater Newcastle; Medical Oncology
      • Wentworthville, New South Wales, Australia, 2145
        • Westmead Hospital; Medical Oncology
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
        • Mater Hospital; Cancer Services
    • Victoria
      • Malvern, Victoria, Australia, 3144
        • Cabrini Medical Centre; Oncology
    • Western Australia
      • Bull Creek, Western Australia, Australia, 6149
        • Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit
  • Belgium
      • Bruxelles, Belgium, 1200
        • Cliniques Universitaires St-Luc
      • Charleroi, Belgium, 6000
        • GHdC Site Notre Dame
      • Leuven, Belgium, 3000
        • UZ Leuven Gasthuisberg
  • Brazil
    • BA
      • Salvador, BA, Brazil, 40050-410
        • Santa Casa de Misericordia de Salvador
    • GO
      • Goiania, GO, Brazil, 74605-070
        • Hospital Araujo Jorge; Departamento de Ginecologia E Mama
    • PR
      • Londrina, PR, Brazil, 86015-520
        • Hospital do Câncer de Londrina
    • RJ
      • Rio de Janeiro, RJ, Brazil, 20560-120
        • Instituto Nacional de Cancer - INCa; Oncologia
    • RS
      • Porto Alegre, RS, Brazil, 90610-000
        • Hospital Sao Lucas - PUCRS
      • Porto Alegre, RS, Brazil, 91350-200
        • Hospital Nossa Senhora da Conceicao
    • SP
      • Santo Andre, SP, Brazil, 09060-650
        • Faculdade de Medicina do ABC - FMABC
      • Sao Paulo, SP, Brazil, 01317-000
        • Hospital Perola Byington
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital
  • Chile
      • Temuco, Chile, 4800827
        • Sociedad de Investigaciones Medicas Ltda (SIM)
  • Costa Rica
      • San José, Costa Rica, 10103
        • Clinica CIMCA
      • San José, Costa Rica, 10108
        • ICIMED Instituto de Investigación en Ciencias Médicas
  • Czechia
      • Brno, Czechia, 656 53
        • Masaryk?v onkologický ústav; Klinika komplexní onkologické pé?e
      • Olomouc, Czechia, 779 00
        • Fakultni nemocnice Olomouc; Onkologicka klinika
  • France
      • Besançon Cedex, France, 25030
        • CHU Besancon - Hôpital Jean Minjoz
      • Bordeaux, France, 33300
        • Polyclinique Bordeaux Nord Aquitaine
      • Dijon, France, 21079
        • Centre Georges Francois Leclerc; Oncologie 3
      • Montpellier cedex 5, France, 34298
        • ICM; Medecine B3
      • Nantes, France, 44202
        • Centre Catherine de Sienne
      • Paris, France, 75475
        • APHP - Hospital Saint Louis
      • Reims CEDEX, France, 51056
        • Institut Jean Godinot; Oncologie Medicale
  • Germany
      • Berlin, Germany, 10707
        • Onkologische Schwerpunktpraxis Kurfürstendamm
      • Freiburg, Germany, 79110
        • Praxis für Interdisziplinäre Onkologie und Hämatologie GbR
      • Hamburg, Germany, 20246
        • Universitätsklinikum Hamburg-Eppendorf; Frauenklinik
      • Homburg/Saar, Germany, 66424
        • Universitätsklinikum des Saarlandes; Klinik f. Frauenheilkunden und Geburtshilfe
      • Köln, Germany, 50679
        • Praxis Dr.med. Katja Ziegler-Löhr
      • Langen, Germany, 63225
        • Dres. Andreas Köhler und Roswitha Fuchs
      • Minden, Germany, 32429
        • Mühlenkreiskliniken; Johannes Wesling Klinikum Minden; Klinik für Frauenheilkunde und Geburtshilfe
      • Recklinghausen, Germany, 45659
        • Oncologianova GmbH - Gesellschaft für Innovationen in der Onkologie
      • Rostock, Germany, 18059
        • Universitätsfrauen- und Poliklinik am Klinikum Suedstadt
      • Würzburg, Germany, 97080
        • Universitätsklinikum Würzburg; Frauenklinik
  • Greece
      • Athens, Greece, 145 64
        • Agioi Anargyroi; 3Rd Dept. of Medical Oncology
      • Athens, Greece, 115 22
        • Anticancer Hospital Ag Savas; 1St Dept of Internal Medicine
      • Thessaloniki, Greece, 546 45
        • Euromedical General Clinic of Thessaloniki; Oncology Department
  • Hungary
      • Budapest, Hungary, 1122
        • Orszagos Onkologial Intezet; Onkologiai Osztaly X
      • Miskolc, Hungary, 3501
        • Borsod-Abauj-Zemplen Megyei Korhaz Es Egyetemi Oktato Korhaz; Onkologiai Osztaly
      • Szeged, Hungary, 6720
        • Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika
      • Szolnok, Hungary, 5004
        • Hetenyi Geza County Hospital; Onkologiai Kozpont
      • Zalaegerszeg, Hungary, 8900
        • Zala County Hospital ICU
  • India
    • Delhi
      • New Delhi, Delhi, India, 110076
        • Indraprastha Apollo Hospitals
      • New Delhi, Delhi, India, 110085
        • Rajiv Gandhi Cancer Inst.&Research Center; Medical Oncology
  • Italy
    • Campania
      • Napoli, Campania, Italy, 80131
        • Istituto Nazionale Tumori Irccs Fondazione g. PASCALE;U.O.C. Oncologia Medica Senologica
    • Emilia-Romagna
      • Bologna, Emilia-Romagna, Italy, 40138
        • Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica
    • Friuli-Venezia Giulia
      • Aviano, Friuli-Venezia Giulia, Italy, 33081
        • Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica
    • Toscana
      • Bagno a Ripoli, Toscana, Italy, 50012
        • Ospedale Santa Maria Annunziata; Oncologia
    • Veneto
      • Padova, Veneto, Italy, 35128
        • IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II
  • Japan
      • Aichi, Japan, 464-8681
        • Aichi Cancer Center Hospital
      • Chiba, Japan, 277-8577
        • National Cancer Center Hospital East
      • Fukuoka, Japan, 811-1395
        • National Hospital Organization Kyushu Cancer Center;Breast Oncology
      • Fukushima, Japan, 960-1295
        • Fukushima Medical University Hospital
      • Hyogo, Japan, 663-8501
        • Hyogo Medical University Hospital
      • Kanagawa, Japan, 241-8515
        • Kanagawa cancer center
      • Kanagawa, Japan, 259-1193
        • Tokai University Hospital
      • Kanagawa, Japan, 216-8511
        • St. Marianna University Hospital
      • Kumamoto, Japan, 862-8655
        • Kumamoto Shinto General Hospital
      • Niigata, Japan, 951-8566
        • Niigata Cancer Center Hospital
      • Okayama, Japan, 700-8558
        • Okayama University Hospital
      • Osaka, Japan, 540-0006
        • National Hospital Organization Osaka National Hospital
      • Osaka, Japan, 589-8511
        • Kinki University Hospital, Faculty of Medicine; Surgery
      • Saitama, Japan, 362-0806
        • Saitama Cancer Center, Breast Oncology
      • Shizuoka, Japan, 411-8777
        • Shizuoka Cancer Center
      • Tokyo, Japan, 142-8666
        • Showa University Hospital; Breast Surgery
      • Tokyo, Japan, 104-0045
        • National Cancer Center Hospital
      • Tokyo, Japan, 135-8550
        • The Cancer Institute Hospital Of JFCR
      • Tokyo, Japan, 104-8560
        • St. Luke's International Hospital
  • Korea, Republic of
      • Goyang-si, Korea, Republic of, 10408
        • National Cancer Center
      • Incheon, Korea, Republic of, 22332
        • Inha University Hospital
      • Seongnam-si, Korea, Republic of, 463-707
        • Seoul National University Bundang Hospital
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital, Yonsei University Health System
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center
  • Mexico
      • Mexico City, Mexico, 03100
        • CENEIT Oncologicos; DENTRO DE CONDOMINIO SAN FRANCISCO
    • Mexico CITY (federal District)
      • Cdmx, Mexico CITY (federal District), Mexico, 06760
        • Centro Medico Dalinde
    • Nuevo LEON
      • Monterrey, Nuevo LEON, Mexico, 66278
        • Centro Medico Zambrano Hellion
    • Yucatan
      • Mérida, Yucatan, Mexico, 97125
        • Merida | Investigacion Clinica
  • North Macedonia
      • Bitola, North Macedonia, 7000
        • Clinical Hospital; Oncology Department
      • Skopje, North Macedonia, 1000
        • PHI University Clinic of Radiotherapy and Oncology; Malignant diseases of thorax
      • Skopje, North Macedonia, 1000
        • PHI University Clinic of Radiotherapy and Oncology; Breast malignancy
  • Peru
      • Arequipa, Peru, 04001
        • Centro Medico Monte Carmelo
      • Callao, Peru, 07021
        • Hospital Daniel Alcides Carrion
      • Lima, Peru, Lima 34
        • Instituto Nacional de Enfermedades Neoplasicas
      • Lima, Peru, 15088
        • Clínica San Gabriel; Unidad de Investigación Oncológica de la Clínica San Gabriel
      • Lima, Peru, 41
        • Oncosalud Sac; Oncología
      • Lima, Peru, 15102
        • Hospital Nacional Cayetano Heredia; Ocología; Servicio de Hematología Oncología Médica
      • San Isidro, Peru, Lima 27
        • Clinica Ricardo Palma
      • Trujillo, Peru, 13014
        • Instituto Regional de Enfermedades Neoplasicas - IREN Norte
  • Poland
      • ?ód?, Poland, 93-338
        • Instyt. Centrum Zdrowia Matki Polki; Klinika Chirurgii Onk. Chorób Piersi z Podod. Onko Klinicznej
      • Gliwice, Poland, 44-101
        • Narodowy Inst.Onkol.im.Sklodowskiej-Curie Panstw.Inst.Bad Gliwice; III Klin. Radioter. i Chemioter.
      • Warszawa, Poland, 02-781
        • Narodowy Instytut Onkologii im. M.Sklodowskiej-Curie; Klinika Nowotworow Piersi i Chirurgii Rekonstr
  • Russian Federation
      • Ivanovo, Russian Federation, 153040
        • Ivanovo regional oncology dispensary
      • Kaluga, Russian Federation, 248007
        • SBIH Kaluga Region Clinical Oncology Dispensary
    • Arhangelsk
      • Arkhangelsk, Arhangelsk, Russian Federation, 163045
        • Arkhangelsk Regional Clinical Oncology Dispensary
    • Moskovskaja Oblast
      • Moscovskaya Oblast, Moskovskaja Oblast, Russian Federation, 143423
        • Moscow City Oncology Hospital #62
      • Moscow, Moskovskaja Oblast, Russian Federation, 125284
        • Federal State Institution, Moscow Research Oncology Institute n.a. P.A. Hertzen; Oncourology
      • Moskva, Moskovskaja Oblast, Russian Federation, 115478
        • Blokhin Cancer Research Center; Combined Treatment
    • Rostov
      • Rostov-on-Don, Rostov, Russian Federation, 344037
        • FSI Rostov research oncological institute of MoH and SD of RF; PAD
    • Sankt Petersburg
      • Saint-Petersburg, Sankt Petersburg, Russian Federation, 197758
        • S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
    • Tatarstan
      • Kazan, Tatarstan, Russian Federation, 420029
        • Clinical Oncology Dispensary of Ministry of Health of Tatarstan
  • Singapore
      • Singapore, Singapore, 119228
        • National University Hospital; National University Cancer Institute, Singapore (NCIS)
      • Singapore, Singapore, 168583
        • National Cancer Centre; Medical Oncology
  • Slovenia
      • Ljubljana, Slovenia, 1000
        • Institute of Oncology Ljubljana
  • South Africa
      • Johannesburg, South Africa, 2196
        • Medical Oncology Centre of Rosebank; Oncology
  • Spain
      • Barcelona, Spain, 08003
        • Hospital del Mar; Servicio de Oncologia
      • Barcelona, Spain, 08036
        • Hospital Clinic Barcelona; Servicio de oncologia
      • Barcelona, Spain, 08035
        • Vall d?Hebron Institute of Oncology (VHIO), Barcelona
      • Guipuzcoa, Spain, 20014
        • Hospital de Donostia; Servicio de Oncologia
      • Madrid, Spain, 28034
        • Hospital Ramon y Cajal; Servicio de Oncologia
      • Madrid, Spain, 28050
        • HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio; Servicio de Oncologia
      • Valencia, Spain, 46010
        • Hospital Clinico Universitario; Oncologia
    • Castellon
      • Castellon de La Plana, Castellon, Spain, 12002
        • Hospital Provincial de Castellon; Servicio de Oncologia
    • Cordoba
      • Córdoba, Cordoba, Spain, 14004
        • Hospital Universitario Reina Sofia; Servicio de Oncologia
    • LA Coruña
      • Santiago de Compostela, LA Coruña, Spain, 15706
        • Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
    • Madrid
      • Majadahonda, Madrid, Spain, 28222
        • Hospital Universitario Puerta de Hierro; Servicio de Oncologia
  • Taiwan
      • Liuying Township, Taiwan, 736
        • Chi Mei Medical Center Liou Ying Campus
      • Taipei, Taiwan, 00112
        • VETERANS GENERAL HOSPITAL; Department of General Surgery
      • Taipei, Taiwan, 100
        • National Taiwan Uni Hospital; General Surgery
      • Taipei City, Taiwan, 11259
        • Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology
  • Turkey
      • Ankara, Turkey, 06490
        • Ankara Bilkent City Hospital
      • Diyarbakir, Turkey, 10000
        • Dicle Uni Medical Faculty; Internal Medicine
      • Istanbul, Turkey, 34384
        • Prof. Dr. Cemil Tascioglu City Hospital; Med Onc
      • Istanbul, Turkey, 34214
        • Medipol University Medical Faculty; Oncology Department
      • Izmir, Turkey, 35360
        • Katip Celebi University Ataturk Training and Research Hospital; Oncology
      • Sakarya, Turkey, 54100
        • Sakarya University Medical School; Medical Oncology
  • Ukraine
      • Dnipropetrovsk, Ukraine, 49102
        • Chemotherapy SI Dnipropetrovsk MA of MOHU
      • Kiev, Ukraine, 03115
        • Kyiv City Clinical Oncological Center, Day Hospital Department for Oncological patients
      • Kiev, Ukraine, 36022
        • National Cancer Institute MOH of Ukraine
      • Lviv, Ukraine, 79031
        • Lviv State Oncological Regional Treatment and Diagnostic Center
  • United Kingdom
      • Cardiff, United Kingdom, CF14 2TL
        • Velindre Cancer Centre
      • Coventry, United Kingdom, CV2 2DX
        • University Hospital coventry; Oncology Department
      • Glasgow, United Kingdom, G12 0YN
        • The Beatson West of Scotland Cancer Centre; Cancer Clinical Trials Unit
      • London, United Kingdom, SW3 6JJ
        • Royal Marsden Hospital - London
      • Plymouth, United Kingdom, PL6 8BT
        • Derriford Hospital
      • Stoke-on-Trent, United Kingdom, ST4 6QG
        • Royal Stoke University Hospital
      • Sutton, United Kingdom, SM2 5PT
        • Royal Marsden Hospital; Dept of Medical Oncology
  • United States
    • California
      • La Jolla, California, United States, 92093
        • UCSD Moores Cancer Center
      • Los Angeles, California, United States, 90033
        • USC Norris Cancer Center
      • Newport Beach, California, United States, 92663
        • USC Norris Cancer Center; USC Oncology Hematology Newport Beach
      • Oakland, California, United States, 94611
        • Kaiser Permanente - Oakland
      • Roseville, California, United States, 95661
        • Kaiser Permanente - Roseville
      • Sacramento, California, United States, 95825
        • Kaiser Permanente Sacramento Medical Center
      • Sacramento, California, United States, 95817
        • UC Davis; Comprehensive Cancer Center
      • San Francisco, California, United States, 94115
        • Kaiser Permanente - San Francisco (2238 Geary)
      • San Francisco, California, United States, 94158
        • UCSF Comprehensive Cancer Ctr
      • San Jose, California, United States, 95119
        • K. Permanente - San Jose
      • San Leandro, California, United States, 94577
        • Kaiser Permanente - San Leandro
      • Santa Clara, California, United States, 95051
        • K. Permanente - Santa Clara
      • South San Francisco, California, United States, 94080
        • Kaiser Permanente - South San Francisco
      • Vallejo, California, United States, 94589
        • Kaiser Permanente - Vallejo
      • Walnut Creek, California, United States, 94596
        • K. Permanente - Walnut Creek
    • Florida
      • Hollywood, Florida, United States, 33021
        • Memorial Regional Hospital
      • Miami Beach, Florida, United States, 33140
        • Mount Sinai Comprehensive Cancer Center
      • Orlando, Florida, United States, 32824
        • UF Health Cancer Center at Orlando Health
      • Pembroke Pines, Florida, United States, 33028
        • Memorial Hospital West
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland
      • Baltimore, Maryland, United States, 21202
        • Mercy Medical Center
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
    • New York
      • Harrison, New York, United States, 10604
        • Memorial Sloan Kettering Cancer Center at Westchester
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • West Clinic
    • Texas
      • Dallas, Texas, United States, 75246
        • Texas Oncology, P.A.
      • Dallas, Texas, United States, 75390
        • UT Southwestern Medical Center; Simmons Comprehensive Cancer Center, Simmons Pharmacy
      • Houston, Texas, United States, 77030
        • Oncology Consultants PA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ipatasertib + Paclitaxel
Drug: 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.
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.
Experimental: Placebo + Paclitaxel
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cohort A: Progression-Free Survival (PFS)
Time Frame: From randomization up to 27 months
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined locally by the investigator through the use of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1), or death from any cause, whichever occurred first, assessed up to 27 months for this outcome measure. 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 on 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.
From randomization up to 27 months
Cohort B: PFS
Time Frame: From randomization up to 24.4 months
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first, assessed up to 24.4 months for this outcome measure. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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 was also considered progression. Abbreviation used in statistical analysis: PI3K=phosphoinositide 3-kinase and mTOR=mammalian target of rapamycin inhibitor.
From randomization up to 24.4 months
Cohort C: PFS
Time Frame: From enrollment up to 31 months
PFS for Cohort C was defined as the time from enrollment to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first, assessed up to 31 months for this outcome measure. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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 was also considered progression.
From enrollment up to 31 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cohort A and B: Objective Response Rate (ORR)
Time Frame: From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B
ORR was defined as percentage of participants with partial response (PR) or complete response (CR) on 2 consecutive occasions ≥4 weeks apart as determined by the investigator using RECIST v.1.1, assessed up to 27 months for Cohort A and up to 24.4 months for Cohort B, for this outcome measure. CR was 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Percentages are rounded off to the nearest decimal point.
From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B
Cohort C: ORR
Time Frame: From enrollment up to 31 months
ORR was defined as percentage of participants with PR or CR on 2 consecutive occasions ≥4 weeks apart as determined by the investigator using RECIST v.1.1, assessed up to 31 months for this outcome measure. CR was 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Percentages are rounded off to the nearest decimal point.
From enrollment up to 31 months
Cohort A and B: Duration of Response (DOR)
Time Frame: From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B
DOR was defined as the time from the first occurrence of a documented OR (CR or PR) to PD, as determined locally by the investigator through the use of RECIST v1.1, or death from any cause, whichever occurred first assessed up to 27 months for Cohort A and up to 24.4 months for Cohort B, for this outcome measure. CR was 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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 was also considered progression.
From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B
Cohort C: DOR
Time Frame: From enrollment up to 31 months
DOR was defined as the time from the first occurrence of a documented OR (CR or PR) to PD, as determined locally by the investigator through the use of RECIST v1.1, or death from any cause, whichever occurred first, assessed up to 31 months for this outcome measure. CR was 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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 was also considered progression.
From enrollment up to 31 months
Cohort A and B: Clinical Benefit Rate (CBR)
Time Frame: From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B
CBR was defined as percentage of participants with an objective response (CR or PR), or stable disease (SD) for at least 24 weeks, as determined by the investigator through the use of RECIST v.1.1. assessed up to From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B for this outcome measure. CR was 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Percentages are rounded off to the nearest decimal point.
From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B
Cohort C: CBR
Time Frame: From enrollment up to 31 months
CBR was defined as percentage of participants with an objective response (CR or PR), or SD for at least 24 weeks, as determined by the investigator through the use of RECIST v.1.1 assessed up to 31 months for this outcome measure. CR was 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Percentages are rounded off to the nearest decimal point.
From enrollment up to 31 months
Overall Survival (OS)
Time Frame: From randomization/ enrollment (Cohort C) up to death from any cause, up to 45 months for Cohort A, up to 46 months for Cohort B and up to 31 months for Cohort C
OS was defined as the time from randomization to death from any cause.
From randomization/ enrollment (Cohort C) up to death from any cause, up to 45 months for Cohort A, up to 46 months for Cohort B and up to 31 months for Cohort C
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Time Frame: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 (cycle length=28 days)
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) is a cancer-specific instrument with 30 questions covering symptoms, functioning, and health-related quality of life (HRQoL). The participant's assessment of overall HRQoL is assessed by using the last 2 questions (29 and 30) of the instrument, with each of these items based on a 7-point scale (1=very poor to 7=excellent), which are then combined into the GHS/QoL multi-item scale. The scores obtained for each question were averaged into a raw score for the scale, and this raw score for the scale was then subsequently linearly transformed to a scale score of 0 to 100, with a high score indicating better GHS/QoL. Negative change from Baseline values in the GHS/QoL change from baseline analysis indicated deterioration in HRQoL and positive values indicated improvement.
Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 (cycle length=28 days)
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Time Frame: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, and 44 (cycle length=28 days)
EORTC QLQ-C30 is a cancer-specific instrument with 30 questions covering symptoms, functioning, and health-related quality of life (HRQoL). The participant's assessment of overall HRQoL is assessed by using the last 2 questions (29 and 30) of the instrument, with each of these items based on a 7-point scale (1=very poor to 7=excellent), which are then combined into the GHS/QoL multi-item scale. The scores obtained for each question were averaged into a raw score for the scale, and this raw score for the scale was then subsequently linearly transformed to a scale score of 0 to 100, with a high score indicating better GHS/QoL. Negative change from Baseline values in the GHS/QoL change from baseline analysis indicated deterioration in HRQoL and positive values indicated improvement.
Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, and 44 (cycle length=28 days)
Cohort B: Time to Deterioration (TTD) in Pain
Time Frame: Baseline up to 24.4 months
Time to deterioration in GHS/HRQoL was defined as the time from randomization to first observed ≥ 11-point increase from Baseline in pain scale score (Question 9 and 19) in EORTC QLQ-C30 linearly transformed GHS/HRQoL scale score, assessed up 24.4 months for this outcome measure. TTD was planned to be assessed only in cohort with HR+/HER2 - breast cancer participants (Cohort B). Questions 9 and 19 that assessed pain, used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). The scores were linearly transformed on a scale of 0 to 100, with higher scores indicating increased severity in symptoms.
Baseline up to 24.4 months
Number of Participants With Adverse Events (AEs)
Time Frame: Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0.
Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
Number of Participants With at Least One Adverse Events of Special Interest (AESI)
Time Frame: Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the NCI CTCAE, Version 4.0. AESI include cases of potential drug-induced liver injury that include an elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law. Suspected transmission of an infectious agent by the study drug, Grade >= 3 fasting hyperglycemia, hepatotoxicity, diarrhea, rash, ALT/AST elevations. Grade >= 2 colitis/enterocolitis.
Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
Cohorts A and B:Plasma Concentration of Ipatasertib
Time Frame: Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days)
Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days)
Cohort C: Plasma Concentration of Ipatasertib
Time Frame: Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days)
Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days)
Cohorts A and B: Plasma Concentration of G-037720
Time Frame: Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days )
G-037720 was a metabolite of ipatasertib.
Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days )
Cohort C: Plasma Concentration of G-037720
Time Frame: Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days )
G-037720 was a metabolite of ipatasertib.
Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days )
Cohort C: 1-year Event-free PFS Rate
Time Frame: From enrollment until the occurrence of disease progression or death from any cause, whichever occurred earlier, up to 1 year
PFS was defined as the time from enrollment to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first. Event-free PFS rate was defined as percentage of participants who did not experience any event and survived at 1 year after enrollment. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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 was also considered progression. Percentages are rounded off to the nearest decimal point. As prespecified in the protocol, this outcome measure was applicable only to Cohort C.
From enrollment until the occurrence of disease progression or death from any cause, whichever occurred earlier, up to 1 year
Cohort C: 1-year Event-free OS Rate
Time Frame: From enrollment up to death from any cause, up to 1 year
OS was defined as the time from enrollment to death from any cause. Event-free OS rate was defined as percentage of participants who did not experience any event and survived at 1 year after enrollment. As prespecified in the protocol, this outcome measure was applicable only to Cohort C. Percentages were rounded off to the nearest decimal.
From enrollment up to death from any cause, up to 1 year
Cohort C: Serum Concentration of Atezolizumab
Time Frame: Day 1 of Cycle 1: 30 minutes post dose, predose on Day 15 of Cycle 1 and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length=28 days)
As prespecified in the protocol, this outcome measure was applicable only to Cohort C.
Day 1 of Cycle 1: 30 minutes post dose, predose on Day 15 of Cycle 1 and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length=28 days)
Cohort C: Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
Time Frame: Up to 45.5 months
The numbers of ADA-positive participants after drug administration were summarized for participants exposed to atezolizumab. As prespecified in the protocol, this outcome measure was applicable only to Cohort C.
Up to 45.5 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

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General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 6, 2018

Primary Completion (Actual)

January 4, 2023

Study Completion (Actual)

January 4, 2023

Study Registration Dates

First Submitted

November 7, 2017

First Submitted That Met QC Criteria

November 7, 2017

First Posted (Actual)

November 9, 2017

Study Record Updates

Last Update Posted (Actual)

March 12, 2024

Last Update Submitted That Met QC Criteria

February 15, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CO40016
  • 2017-001548-36 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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