Ipatasertib Plus Abiraterone Plus Prednisone/Prednisolone, Relative to Placebo Plus Abiraterone Plus Prednisone/Prednisolone in Adult Male Patients With Metastatic Castrate-Resistant Prostate Cancer (IPATential150)

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial Testing Ipatasertib Plus Abiraterone Plus Prednisone/Prednisolone, Relative to Placebo Plus Abiraterone Plus Prednisone/Prednisolone in Adult Male Patients With Asymptomatic or Mildly Symptomatic, Previously Untreated, Metastatic Castrate-Resistant Prostate Cancer

The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of ipatasertib plus abiraterone and prednisone/prednisolone compared with placebo plus abiraterone and prednisone/prednisolone in participants with metastatic castrate-resistant prostate cancer (mCRPC).

Study Overview

• Status: Completed
• Conditions: Metastatic Prostate Cancer
• Intervention / Treatment: Drug: Abiraterone; Drug: Placebo; Drug: Prednisone/Prednisolone; Drug: Ipatasertib

• Study Type: Interventional
• Enrollment (Actual): 1101
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Macquarie University, New South Wales, Australia, 2109
      • Macquarie University Hospital
  • South Australia
    • Kurralta Park, South Australia, Australia, 5037
      • Adelaide Cancer Centre
  • Victoria
    • EAST Bentleigh, Victoria, Australia, VIC 3165
      • Monash Medical Centre
    • Melbourne, Victoria, Australia, 3000
      • Peter Maccallum Cancer Centre
    • Melbourne, Victoria, Australia, 3128
      • Eastern Health
• Austria
  • Graz, Austria, 8036
    • Lkh-Univ. Klinikum Graz
  • Linz, Austria, 4020
    • Ordensklinikum Linz Elisabethinen
  • Salzburg, Austria, 5020
    • Landeskrankenhaus Salzburg
• Belgium
  • Gent, Belgium, 9000
    • UZ Gent
  • Kortrijk, Belgium, 8500
    • AZ Groeninge
  • Liège, Belgium, 4000
    • CHU Sart-Tilman
• Brazil
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 31190-131
      • Hospital Luxemburgo
  • Rio Grande Do Norte
    • Natal, Rio Grande Do Norte, Brazil, 59040150
      • Liga Norte Riograndense Contra o Câncer
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 91350-200
      • Hospital Nossa Senhora da Conceicao
  • São Paulo
    • Sao Paulo, São Paulo, Brazil, 01246-000
      • Instituto do Cancer do Estado de Sao Paulo - ICESP
• Canada
  • Quebec, Canada, G1J 1Z4
    • CHU de Québec - Université Laval - Hôtel-Dieu de Québec
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA-Vancouver Cancer Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Hamilton Health Sciences - Juravinski Cancer Centre
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health Oshawa
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Center
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Research Institute
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H4J 1C5
      • Hopital Sacre-Coeur Research Centre
• China
  • Beijing Shi, China, 100050
    • Beijing Friendship Hospital Affiliated of Capital University of Medical Science
  • Nanjing, China, 210009
    • Jiangsu Cancer Hospital
  • Nanjing, China, 210029
    • Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center
  • Shanghai, China, 200032
    • Zhongshan Hospital Fudan University
  • Xi'an, China, 710061
    • First Affiliated Hospital of Medical College of Xi'an Jiaotong University
• Costa Rica
  • San Jose, Costa Rica, 10103
    • Clinica CIMCA
  • San Jose, Costa Rica, 1007
    • ICIMED Instituto de Investigación en Ciencias Médicas
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital, Urologisk Afd. K
  • Odense, Denmark, 5000
    • Odense Universitetshospital, Onkologisk Afdeling R
• France
  • Angers, France, 49055
    • ICO Paul Papin
  • Caen, France, 14076
    • Centre Francois Baclesse
  • Clermont Ferrand, France, 63011
    • Centre Jean Perrin
  • La Roche Sur Yon, France, 85025
    • CHD Vendee
  • Lille, France, 59000
    • Hôpital Claude Huriez
  • Montpellier, France, 34298
    • Institut Régional du Cancer Montpellier
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Nimes, France, 30029
    • Institut de cancerologie du Gard
  • Paris, France, 75674
    • Institut Mutualiste Montsouris
  • Poitiers, France, 86021
    • CHU Poitiers
  • Saint-Mande, France, 94160
    • Hopital d'Instruction des Armees de Begin
  • Suresnes, France, 92151
    • Hôpital Foch
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Greece
  • Athens, Greece, 155 62
    • IASO General Hospital of Athens
  • Athens, Greece, 115 28
    • Alexandras Hospital
  • Patras, Greece, 265 04
    • University Hospital of Patras Medical Oncology
  • Thessaloniki, Greece, 546 29
    • Papageorgiou General Hospital
• Hungary
  • Budapest, Hungary, 1122
    • Orszagos Onkologiai Intezet
  • Budapest, Hungary, 1145
    • Budapesti Uzsoki Utcai Korhaz
  • Budapest, Hungary, 1082
    • Semmelwies University of Medicine
  • Debrecen, Hungary, H4032
    • Debreceni Egyetem Klinikai Kozpont
  • Miskolc, Hungary, 3526
    • B-A-Z County Hospital
• Ireland
  • Cork, Ireland, DUMMY_VALUE
    • Cork University Hospital
  • Dublin, Ireland, 7
    • Mater Private Hospital
  • Dublin, Ireland, 7
    • Mater Misericordiae Uni Hospital
  • Dublin, Ireland, 24
    • Adelaide & Meath Hospital, Dublin, Incorporating the National Children's Hospital
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Kfar-Saba, Israel, 4428164
    • Meir Medical Center
  • Petach Tikva, Israel, 4941492
    • Belinson Medical Center, Division of Oncology
  • Ramat Gan, Israel, 5262000
    • Chaim Sheba medical center, Oncology division
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Istituto Nazionale Tumori Irccs Fondazione g. Pascale
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • I.R.S.T Srl IRCCS
    • Modena, Emilia-Romagna, Italy, 41100
      • A.O. Universitaria Policlinico Di Modena
  • Lazio
    • Roma, Lazio, Italy, 00152
      • Azienda Ospedaliera San Camillo Forlanini
  • Lombardia
    • Cremona, Lombardia, Italy, 26100
      • A.O. Istituti Ospitalieri - Cremona
    • Milano, Lombardia, Italy, 20133
      • Irccs Istituto Nazionale Dei Tumori (Int)
    • Milano, Lombardia, Italy, 20153
      • A.O. San Carlo Borromeo
    • Rozzano, Lombardia, Italy, 20089
      • Istituto Clinico Humanitas
  • Toscana
    • Arezzo, Toscana, Italy, 52100
      • Ospedale Area Aretina Nord
    • Firenze, Toscana, Italy, 50139
      • Azienda Ospedaliero-Universitaria Careggi
  • Trentino-Alto Adige
    • Trento, Trentino-Alto Adige, Italy, 38122
      • Ospedale di Trento-Presidio Ospedaliero Santa Chiara
• Japan
  • Aichi, Japan, 466-8560
    • Nagoya University Hospital
  • Aomori, Japan, 036-8563
    • Hirosaki University Hospital
  • Chiba, Japan, 285-8741
    • Toho University Sakura Medical Center
  • Chiba, Japan, 277-8577
    • National Cancer Center East
  • Gunma, Japan, 371-8511
    • Gunma University Hospital
  • Hokkaido, Japan, 003-0804
    • National Hospital Organization Hokkaido Cancer Center
  • Ishikawa, Japan, 920-8641
    • Kanazawa University Hospital
  • Kanagawa, Japan, 252-0375
    • Kitasato University Hospital
  • Kanagawa, Japan, 232-0024
    • Yokohama City University Medical Center
  • Kochi, Japan, 783-8505
    • Kochi Medical School Hospital
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital
  • Kyoto, Japan, 602-8566
    • University Hospital Kyoto Prefectural University of Medicine
  • Niigata, Japan, 951-8520
    • Niigata University Medical & Dental Hospital
  • Osaka, Japan, 589-8511
    • Kindai University Hospital
  • Tokyo, Japan, 160-8582
    • Keio University Hospital
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital Of JFCR
  • Tokyo, Japan, 113-8603
    • Nippon Medical School Hospital
  • Tokyo, Japan, 181-8611
    • Kyorin University Hospital
  • Yamaguchi, Japan, 755-8505
    • Yamaguchi University Hospital
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 10408
    • National Cancer Center
  • Gyeonggi-do, Korea, Republic of, 13620
    • Seoul National University Bundang 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
  • Seoul, Korea, Republic of, 06273
    • Gangnam Severance Hospital
• Mexico
  • Durango, Mexico, 34000
    • Consultorio de Especialidad en Urologia Privado
  • Mexico CITY (federal District)
    • Mexico City, Mexico CITY (federal District), Mexico, 11850
      • Hospital Angeles Mocel
  • Sinaloa
    • Culiacan, Sinaloa, Mexico, DUMMY_VALUE
      • Centro Medico Culiacan SA de CV
  • Yucatan
    • Mérida, Yucatan, Mexico, 97070
      • Medical Care & Research
• Norway
  • Grålum, Norway, 1714
    • Sykehuset Østfold Kalnes
  • Lørenskog, Norway, 1478
    • Akershus Universitetssykehus HF
• Poland
  • ?ód?, Poland, 93-513
    • Woj. Wielospec. Centrum Onkologii i Traumatologii
  • Opole, Poland, 45-060
    • SPZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarawskiego
  • Warszawa, Poland, 04-073
    • Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.
  • Warszawa, Poland, 02-781
    • Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie
  • Wroclaw, Poland, 53-413
    • Dolno?L?Skie Centrum Onkologii, Pulmonologii I Hematologii
• Portugal
  • Coimbra, Portugal, 3000-075
    • HUC
  • Lisboa, Portugal, 1649-035
    • Hospital de Santa Maria
  • Porto, Portugal, 4200-072
    • IPO do Porto
• Russian Federation
  • Altaj
    • Barnaul, Altaj, Russian Federation, 656049
      • Altai Regional Oncological Center
  • Moskovskaja Oblast
    • Moscovskaya Oblast, Moskovskaja Oblast, Russian Federation, 143423
      • Moscow City Oncology Hospital #62
    • Moscow, Moskovskaja Oblast, Russian Federation, 115478
      • Blokhin Cancer Research Center
  • Niznij Novgorod
    • Nizhny Novgorod, Niznij Novgorod, Russian Federation, 603001
      • Privolzhsk Regional Medical Center
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic I Provincial
  • Barcelona, Spain, 08041
    • Hospital De La Santa Creu I Sant Pau
  • Cordoba, Spain, 14004
    • Hospital Universitario Reina Sofía
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Malaga, Spain, 29010
    • Hospital Clinico Universitario Virgen de la Victoria
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Institut Catala d?Oncologia Hospital Germans Trias i Pujol
    • Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Insititut Catala D'Oncologia
    • Sabadell, Barcelona, Spain, 08208
      • Corporacio Sanitaria Parc Tauli
  • Islas Baleares
    • Palma De Mallorca, Islas Baleares, Spain, 07014
      • Hospital Universitario Son Espases
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria de Navarra
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical Uni Chung-Ho Hospital
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital-Linkou
• Thailand
  • Bangkok, Thailand, 10330
    • Chulalongkorn Hospital
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital
  • Bangkok, Thailand, 10700
    • Faculty of Med. Siriraj Hosp.
  • Chiangmai, Thailand, 50200
    • Maharaj Nakorn ChiangMai Hospital
• United Kingdom
  • Blackburn, United Kingdom, BB2 3HH
    • Royal Blackburn Hospital
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Northwood, United Kingdom, HA6 2RN
    • Mount Vernon & Watford Trust Hospital
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital
  • Wolverhampton, United Kingdom, WV10 0QP
    • Royal Wolverhampton hospital
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Ironwood Cancer & Research Centers
    • Scottsdale, Arizona, United States, 85025
      • Mayo Clinic Arizona
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90033
      • USC Norris Cancer Center
    • Orange, California, United States, 92868
      • UC Irvine Medical Center
    • Palo Alto, California, United States, 94305
      • Stanford University
    • San Francisco, California, United States, 94115
      • Pacific Hematology Oncology Associates
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Cancer Pavilion
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Lynn Cancer Institute/Boca Raton Regional Hospital
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute of Baptist Health, Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
  • Illinois
    • Peoria, Illinois, United States, 61615
      • Illinois Cancer Care
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Associates in Oncology/Hematology P.C.
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute..
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • HCA Midwest Division
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Urology Cancer Center & GU Research Network
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack Univ Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Tualatin, Oregon, United States, 97062
      • Northwest Cancer Specialists, P.C.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Charleston Oncology, P .A
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
  • Texas
    • The Woodlands, Texas, United States, 77380
      • Texas Oncology - Gulf Coast
  • Utah
    • Salt Lake City, Utah, United States, 84132-0001
      • Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Eastern Collaborative Oncology Group (ECOG) performance status of 0 or 1 at screening
• Adequate hematologic and organ function within 28 days before the first study treatment
• Ability to comply with the study protocol, in the investigator's judgment
• Willingness and ability of participants to use the electronic device to report selected study outcomes; Caregivers and site staff can assist with patient diary input but patient must be able to independently comprehend and answer the questionnaires
• Life expectancy of at least 6 months
• Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm
• For enrollment into the China extension cohort, residence in the People's Republic of China

Disease-specific Inclusion Criteria:

• Histologically confirmed prostate adenocarcinoma without neuroendocrine differentiation or small-cell features
• Consent to provide a formalin-fixed paraffin-embedded (FFPE) tissue block (preferred) or a minimum of 15 (20 preferred) freshly cut unstained tumor slides from the most recently collected, available tumor tissue accompanied by an associated pathology report (with tumor content information, Gleason score, and disease staging) for PTEN IHC and NGS testing and for other protocol-mandated secondary and exploratory assessments. If only 12-14 slides are available, the patient may still be eligible for the study, after discussion with and approval by the Medical Monitor. Cytologic or fine-needle aspiration samples are not acceptable. Tumor tissue from bone metastases is not acceptable
• A valid PTEN IHC result (testingcentral laboratory tested with results directly sent to IxRS) (e.g., participants with an "invalid" or "failed" PTEN IHC result are not permitted to enroll)
• Metastatic disease documented prior to randomization by clear evidence of bone lesions on bone scan and/or measurable soft tissue disease by computed tomography (CT) and/or magnetic resonance imaging (MRI) (at least one target lesion) according to RECIST v1.1
• Asymptomatic or mildly symptomatic form of prostate cancer
• Progressive disease before initiating study treatment
• Ongoing androgen deprivation with gonadotropin-releasing hormone (GnRH) analog or bilateral orchiectomy, with serum testosterone <= 50 ng/dL (<= 1.7 nmol/L) within 28 days before randomization

Exclusion Criteria:

• Inability or unwillingness to swallow whole pills
• History of malabsorption syndrome or other condition that would interfere with enteral absorption
• Clinically significant history of liver disease consistent with Child-Pugh Class B or C, including cirrhosis, current alcohol abuse, or current known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Need of more than 10 mg/day of prednisone or an equivalent dose of other anti-inflammatory corticosteroids as a current systemic corticosteroid therapy to treat a chronic disease (e.g., rheumatic disorder)
• Active infection requiring intravenous (IV) antibiotics within 14 days before Day 1, Cycle 1
• Immunocompromised status because of current known active infection with HIV or because of the use of immunosuppressive therapies for other conditions
• Major surgical procedure or significant traumatic injury within 28 days prior to Day 1, Cycle 1, or anticipation of the need for major surgery during study treatment
• History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), untreated coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), myocardial infarction or atrial thrombotic events within the past 6 months, severe unstable angina, New York Heart Association Class III and IV heart disease or depressed left ventricular ejection fraction (LVEF; previously documented LVEF < 50% without documentation of recovery), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome
• History of another malignancy within 5 years prior to randomization, except for either adequately treated non-melanomatous carcinoma of the skin, adequately treated melanoma in situ, adequately treated non-muscle-invasive urothelial carcinoma of the bladder (Tis, Ta, and low grade T1 tumors), or other malignancies where the patient has undergone potentially curative therapy with no evidence of disease and are deemed by the treating physician to have a recurrence rate of <5% at 5 years
• Any other diseases, cardiovascular, pulmonary, or metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the participants at high risk from treatment complications.

Disease-Specific Exclusion Criteria:

• Pathologic findings consistent with small-cell or neuroendocrine carcinoma of the prostate
• Any therapy including chemotherapy (e.g., docetaxel) or biological therapy (e.g., vaccine, immunotherapy) for the treatment of castration-resistant prostate cancer. Previous treatment with flutamide, steroidal anti-androgens, androgens, estrogens, bicalutamide, nilutamide, or 5-α reductase inhibitor is permitted.
• Use of opioid medications for cancer-related pain, including codeine and dextropropoxyphene, currently or any time within 4 weeks of Day 1, Cycle 1
• Prior treatment with abiraterone or other known potent CYP17 inhibitors (e.g., ketoconazole, orteronel) or investigational agents that block androgen synthesis. Previous treatment with itraconazole and fluconazole is permitted.
• Prior treatment with enzalutamide or other potent androgen-receptor blockers, approved or experimental (e.g., ARN-509, ODM-201, or galeterone)
• Prior treatment with flutamide (Eulexin®), steroidal anti-androgens (e.g., cyproterone acetate, chlormadinone acetate), androgens, or estrogens treatment within 4 weeks of Cycle 1, Day 1
• Prior treatment with bicalutamide (Casodex®) or nilutamide (Nilandron®) within 6 weeks of Cycle 1, Day 1
• Prior treatment with 5-alpha reductase inhibitors within 4 weeks of Cycle 1, Day 1
• Prior treatment with systemic radiopharmaceuticals (e.g., radium-223 and strontium-89). Radiopharmaceuticals for the purpose of imaging are permitted. Focal palliative radiation to treat cancer-related pain is permitted provided that the last treatment with radiation is at least 14 days prior to Cycle 1, Day 1.
• Prior treatment with approved or experimental therapeutic agents with known inhibition of the PI3K pathway, including PI3K inhibitors, AKT inhibitors, and mTOR inhibitors
• Administration of an investigational therapeutic agent within 28 days of Cycle 1, Day 1
• Known untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsant medications or corticosteroids for symptomatic control); a CT or MRI scan of the brain will be performed at screening if required by the local health authority
• Any chronic therapy or use of food supplements that are strong CYP3A4/5 inducers or inhibitors or sensitive substrates of CYP3A or CYP2D6 with a narrow therapeutic window

Abiraterone-Specific Exclusion Criteria:

• Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 95 mmHg)
• History of pituitary or adrenal dysfunction
• Any ongoing cardiac arrhythmias (including atrial fibrillation) that require medical therapy

Ipatasertib-Specific Exclusion Criteria:

• Type 1 or Type 2 diabetes mellitus requiring insulin at study entry
• History of inflammatory bowel disease (e.g., Crohn disease and ulcerative colitis), active bowel inflammation (e.g., diverticulitis)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Placebo + Abiraterone; Participants received Placebo plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.	Drug: Abiraterone; Oral tablets of abiraterone, 1000 mg QD, taken on an empty stomach and swallowed whole with water.; Drug: Placebo; Oral tablets (matched to ipatasertib appearance), given QD beginning on Day 1 of Cycle 1 until disease progression or intolerable toxicity.; Drug: Prednisone/Prednisolone; Oral tablets of 5 mg, taken twice daily (BID) until disease progression or intolerable toxicity.
Experimental: Ipatasertib + Abiraterone; Participants received Ipatasertib plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.	Drug: Abiraterone; Oral tablets of abiraterone, 1000 mg QD, taken on an empty stomach and swallowed whole with water.; Drug: Prednisone/Prednisolone; Oral tablets of 5 mg, taken twice daily (BID) until disease progression or intolerable toxicity.; Drug: Ipatasertib; Oral tablets, 400 mg, given once daily (QD) beginning on Day 1 of Cycle 1 until disease progression or intolerable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed Radiographic Progression-free Survival (rPFS), Per Prostate Cancer Working Group 3 (PCWG3) Criteria in Phosphatase and Tensin Homolog (PTEN) Loss Population	rPFS was defined as time from date of randomization to the first occurrence of documented disease progression (PD), as assessed by the investigator with use of the PCWG3 criteria or death from any cause, whichever occurs first. PD for soft tissue was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 millimeters (mm) in the SOD of target lesions; progression of non-target lesions; the appearance of one or more new lesions according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) criteria. PD for bone lesions was defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later according to the PCWG3 criteria. The Kaplan-Meier (KM) estimate was used to determine the median rPFS.	Up to approximately 32 months
Investigator-assessed rPFS, Per PCWG3 Criteria in ITT Population	rPFS was defined as time from date of randomization to the first occurrence of documented PD, as assessed by the investigator with use of the PCWG3 criteria or death from any cause, whichever occurs first. PD for soft tissue was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the SOD of target lesions; progression of non-target lesions; the appearance of one or more new lesions according to RECIST v1.1 criteria. PD for bone lesions was defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later according to the PCWG3 criteria. The KM estimate was used to determine the median rPFS.	Up to approximately 32 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentrations of Ipatasertib at Specified Timepoints	Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants.	1-3 hours post-dose (Cycle 1, Day 1; Cycle 1 Day 15 and Cycle 3 Day 1) and pre-dose at steady state (Cycle 1 Day 15, Cycle 3 Day 1, Cycle 6 Day 1) (each cycle length= 28 days)
Plasma Concentrations of Abiraterone at Specified Timepoints	Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants.	Pre-dose at steady state in Cycle 1, Day 15 and Cycle 3 Day 1 (each cycle length= 28 days)
Overall Survival (OS) in PTEN-loss Population	OS was defined as the time from randomization to death due to any cause. KM estimates were used to determine the median OS.	Up to approximately 6.5 years
OS in ITT Population	OS was defined as the time from randomization to death due to any cause. KM estimates were used to determine the median OS.	Up to approximately 6.5 years
Time to Pain Progression in PTEN-loss Population	Time to pain progression was defined as the time from randomization to the first occurrence of confirmed clinically meaningful cancer-related pain progression event. Cancer-related pain progression refers to pain onset for participants who were asymptomatic at baseline or pain worsening for those who were mildly symptomatic at baseline. Pain severity was graded on a 10-point numeric rating scale [NRS], with 0=no pain and 10=severe pain. Pain severity progression was defined as a ≥ 2-point absolute increase from baseline. KM estimates were used to determine the median time to pain progression.	Up to approximately 5.5 years
Time to Pain Progression in ITT Population	Time to pain progression was defined as the time from randomization to the first occurrence of confirmed clinically meaningful cancer-related pain progression event. Cancer-related pain progression refers to pain onset for participants who were asymptomatic at baseline or pain worsening for those who were mildly symptomatic at baseline. Pain severity was graded on a 10-point NRS, with 0=no pain and 10=severe pain. Pain severity progression was defined as a ≥ 2-point absolute increase from baseline. KM estimates were used to determine the median time to pain progression.	Up to approximately 5.5 years
Time to Initiation of Cytotoxic Chemotherapy for Prostate Cancer (PC) in PTEN-loss Population	Time to initiation of cytotoxic chemotherapy was defined as the time interval from the date of randomization to the date of initiation of cytotoxic chemotherapy (use of antineoplastic agents: docetaxel, cabazitaxel, mitoxantrone, estramustine, cisplatin, carboplatin, cyclophosphamide, doxorubicin, mitomycin, irinotecan, 5-fluorouracil, gemcitabine, or etoposide) for PC. KM estimates were used to determine the median time to initiation of cytotoxic chemotherapy.	Up to approximately 5.5 years
Time to Initiation of Cytotoxic Chemotherapy for PC in ITT Population	Time to initiation of cytotoxic chemotherapy was defined as the time interval from the date of randomization to the date of initiation of cytotoxic chemotherapy (use of antineoplastic agents: docetaxel, cabazitaxel, mitoxantrone, estramustine, cisplatin, carboplatin, cyclophosphamide, doxorubicin, mitomycin, irinotecan, 5-fluorouracil, gemcitabine, or etoposide) for PC. KM estimates were used to determine the median time to initiation of cytotoxic chemotherapy.	Up to approximately 5.5 years
Time to Function Deterioration Per European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Physical Function (PF) Scale and Role Function (RF) Scale in PTEN-loss Population	Time to function deterioration=time from date of randomization to date of 10-point or more score decrease on either EORTC QLQ-C30 5-item PF/2-item RF scale scores, held for two consecutive assessments or death within 28 days, whichever occurs first. EORTC QLQ-C30 consists of 30 questions that assess 5 aspects of participant functioning (physical,emotional,role,cognitive&social), 3 symptom scales (fatigue,nausea&vomiting,pain), global health/quality of life (GHS/QoL)&6 single items (dyspnea,insomnia,appetite loss,constipation,diarrhea&financial difficulties). PF scale has 5 questions about participants physical functioning&daily activities. RF scale has 2 questions about work/daily activities&hobbies/leisurely activities. PF&RF are scored on a 4-point scale (1=Not at All to 4=Very Much). Obtained scores are linearly transformed to score range of 0-100, where higher scores indicate a higher response level (better PF)&better functioning/support.	Up to approximately 5.5 years
Time to Function Deterioration Per EORTC QLQ-C30 PF Scale and RF Scale in ITT Population	Time to function deterioration=time from date of randomization to date of 10-point or more score decrease on either EORTC QLQ-C30 5-item PF/2-item RF scale scores, held for two consecutive assessments or death within 28 days, whichever occurs first. EORTC QLQ-C30 consists of 30 questions that assess 5 aspects of participant functioning (physical,emotional,role,cognitive & social), 3 symptom scales (fatigue,nausea&vomiting,pain), GHS/QoL & 6 single items (dyspnea,insomnia,appetite loss,constipation,diarrhea & financial difficulties). PF scale has 5 questions about participants physical functioning & daily activities. RF scale has 2 questions about work/daily activities & hobbies/leisurely activities. PF&RF are scored on a 4-point scale (1=Not at All to 4=Very Much). Obtained scores are linearly transformed to score range of 0-100, where higher scores indicate a higher response level (better PF) & better functioning/support.	Up to approximately 5.5 years
Time to Prostate-specific Antigen (PSA) Progression, Per the PCWG3 Criteria in PTEN-loss Population	Time to PSA progression was defined as the time from the date of randomization to the first occurrence of PSA progression, per the PCWG3 criteria. PSA progression was defined as a PSA increase that was ≥ 25% and ≥ 2 nanograms per milliliters (ng/mL) above the baseline or the nadir, which was confirmed by a second value ≥ 3 weeks later. KM estimate was used to determine the median time to PSA.	Up to approximately 5.5 years
Time to PSA Progression, Per the PCWG3 Criteria in ITT Population	Time to PSA progression was defined as the time from the date of randomization to the first occurrence of PSA progression, per the PCWG3 criteria. PSA progression was defined as a PSA increase that was ≥ 25% and ≥ 2 ng/mL above the baseline or the nadir, which was confirmed by a second value ≥ 3 weeks later. KM estimate was used to determine the median time to PSA.	Up to approximately 5.5 years
Time to First Opioid Use in PTEN-loss Population	Time to first opioid use was defined as the time interval from the date of randomization to the date of an initiation of opioid analgesic use for cancer-related pain, and consumption reported on at least 7 consecutive days. KM estimate was used to determine the median time to first opioid use.	Up to approximately 5.5 years
Time to First Opioid Use in ITT Population	Time to first opioid use was defined as the time interval from the date of randomization to the date of an initiation of opioid analgesic use for cancer-related pain, and consumption reported on at least 7 consecutive days. KM estimate was used to determine the median time to first opioid use.	Up to approximately 5.5 years
Time to Symptomatic Skeletal Event (SSE) in PTEN-loss Population	Time to SSE was defined as the time from randomization to the first occurrence of an SSE. A SSE was defined using one of the following: use of external-beam radiotherapy to relieve skeletal symptoms (including initiation of radium-223 to treat symptoms of bone metastases); occurrence of a new symptomatic pathological bone fracture (vertebral or non-vertebral); clinically apparent occurrence of spinal cord compression, or a tumor-related orthopedic surgical intervention. KM estimates were used to determine the median time to SSE.	Up to approximately 5.5 years
Time to SSE in ITT Population	Time to SSE was defined as the time from randomization to the first occurrence of an SSE. A SSE was defined using one of the following: use of external-beam radiotherapy to relieve skeletal symptoms (including initiation of radium-223 to treat symptoms of bone metastases); occurrence of a new symptomatic pathological bone fracture (vertebral or non-vertebral); clinically apparent occurrence of spinal cord compression, or a tumor-related orthopedic surgical intervention. KM estimates were used to determine the median time to SSE.	Up to approximately 5.5 years
Objective Response Rate (ORR) Per RECIST V1.1 and PCWG3 Criteria in Participants With Measurable Disease in PTEN-loss Population	ORR was defined as the percentage of participants who had an objective response (OR) with measurable disease at baseline. An OR was defined as a complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator using RECIST v1.1 and PCWG3 criteria in participants with measurable disease at baseline. CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. An estimate of ORR was calculated for each treatment arm, and its 95% CI was calculated using the Clopper-Pearson method. Percentages have been rounded off.	Up to approximately 5.5 years
ORR Per RECIST V1.1 and PCWG3 Criteria in Participants With Measurable Disease in ITT Population	ORR was defined as the percentage of participants who had an OR with measurable disease at baseline. An OR was defined as a CR or PR on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator using RECIST v1.1 and PCWG3 criteria in participants with measurable disease at baseline. CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. An estimate of ORR was calculated for each treatment arm, and its 95% CI was calculated using the Clopper-Pearson method. Percentage have been rounded off.	Up to approximately 5.5 years
Duration of Confirmed Response (DOCR) in PTEN-loss Population	DOCR was defined as the time from the first documented OR (CR or PR) to documented PD as determined by the investigator using RECIST v1.1 and PCWG3 criteria, or death from any cause, whichever occurred first. CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the SOD of target lesions; progression of non-target lesions; the appearance of one or more new lesions. DOR was estimated using the KM methodology.	Up to approximately 5.5 years
DOCR in ITT Population	DOCR was defined as the time from the first documented OR (CR or PR) to documented PD as determined by the investigator using RECIST v1.1 and PCWG3 criteria, or death from any cause, whichever occured first. CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the SOD of target lesions; progression of non-target lesions; the appearance of one or more new lesions. DOR was estimated using the KM methodology.	Up to approximately 5.5 years
PSA Response Rate in PTEN-loss Population	PSA response rate was defined as the percentage of participants achieving a PSA decline ≥ 50% from baseline. Participants without a post-baseline PSA assessment were considered to be non-responders. Percentages have been rounded off.	Up to approximately 5.5 years
PSA Response Rate in ITT Population	PSA response rate was defined as the percentage of participants achieving a PSA decline ≥ 50% from baseline. Participants without a post-baseline PSA assessment were considered to be non-responders. Percentages have been rounded off.	Up to approximately 5.5 years
Investigator-assessed rPFS Per PCWG3 Criteria in PTEN-loss Population by Next-generation Sequencing (NGS)	rPFS was defined as time from date of randomization to the first occurrence of documented PD, as assessed by the investigator using the PCWG3 criteria or death from any cause, whichever occurs first. PD for soft tissue was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the SOD of target lesions; progression of non-target lesions; the appearance of one or more new lesions. PD for bone lesions was defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later.	Up to approximately 32 months
Percentage of Participants With Adverse Events (AEs)	An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), 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 were also considered as AEs. Percentages have been rounded off.	Up to 28 days after last study drug administration (approximately 6.5 years)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• Kotani N, Wilkins JJ, Wade JR, Dang S, Sutaria DS, Yoshida K, Sundrani S, Ding H, Garcia J, Hinton H, Sane R, Chanu P. Characterization of exposure-response relationships of ipatasertib in patients with metastatic castration-resistant prostate cancer in the IPATential150 study. Cancer Chemother Pharmacol. 2022 Dec;90(6):511-521. doi: 10.1007/s00280-022-04488-2. Epub 2022 Oct 28.
• Sweeney C, Bracarda S, Sternberg CN, Chi KN, Olmos D, Sandhu S, Massard C, Matsubara N, Alekseev B, Parnis F, Atduev V, Buchschacher GL Jr, Gafanov R, Corrales L, Borre M, Stroyakovskiy D, Alves GV, Bournakis E, Puente J, Harle-Yge ML, Gallo J, Chen G, Hanover J, Wongchenko MJ, Garcia J, de Bono JS. Ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer (IPATential150): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2021 Jul 10;398(10295):131-142. doi: 10.1016/S0140-6736(21)00580-8.

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2017
• Primary Completion (Actual): March 16, 2020
• Study Completion (Actual): April 24, 2024

Study Registration Dates

• First Submitted: March 2, 2017
• First Submitted That Met QC Criteria: March 2, 2017
• First Posted (Actual): March 7, 2017

Study Record Updates

• Last Update Posted (Actual): June 6, 2025
• Last Update Submitted That Met QC Criteria: May 19, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Metastatic Castrate-Resistant Prostate Cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Protein Kinase Inhibitors; Prednisone; Prednisolone; Ipatasertib
• Other Study ID Numbers: CO39303; 2016-004429-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No