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: Active, not recruiting
• 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 Park, New South Wales, Australia, 2109
      • Macquarie University Hospital
  • South Australia
    • Kurralta Park, South Australia, Australia, 5037
      • Adelaide Cancer Centre
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre; Oncology
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
    • Melbourne, Victoria, Australia, 3128
      • Eastern Health; GU - Oncology
• Austria
  • Graz, Austria, 8036
    • LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie
  • Linz, Austria, 4020
    • Ordensklinikum Linz Elisabethinen; Abteilung für Urologie und Andrologie
  • Salzburg, Austria, 5020
    • Landeskrankenhaus Salzburg; Universitätsklinik für Urologie und Andrologie der PMU
• Belgium
  • Gent, Belgium, 9000
    • UZ Gent
  • Kortrijk, Belgium, 8500
    • Az Groeninge
  • Liège, Belgium, 4000
    • CHU Sart-Tilman
• Brazil
  • MG
    • Belo Horizonte, MG, Brazil, 31190-131
      • Hospital Luxemburgo; Oncologia
  • RN
    • Natal, RN, Brazil, 59040150
      • Liga Norte Riograndense Contra O Cancer
  • RS
    • Porto Alegre, RS, Brazil, 90040-373
      • Hospital Nossa Senhora da Conceicao
  • SP
    • Sao Paulo, SP, 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; Oncology
    • Toronto, Ontario, Canada, M5G 1Z5
      • 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 City, China, 211100
    • Jiangsu Cancer Hospital
  • Nanjing City, China, 210008
    • Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
  • Shanghai, China, 200032
    • Zhongshan Hospital Fudan University
  • Shanghai City, China, 200120
    • Fudan University Shanghai Cancer Center
  • Xi'an, China, 710061
    • First Affiliated Hospital of Medical College of Xi'an Jiaotong University
• Costa Rica
  • San José, Costa Rica, 10103
    • Clinica CIMCA
  • San José, Costa Rica, 10108
    • ICIMED Instituto de Investigación en Ciencias Médicas
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital, Urologisk Afd. K
  • Odense C, Denmark, 5000
    • Odense Universitetshospital, Onkologisk Afdeling R
• France
  • Angers, France, 49055
    • ICO Paul Papin; Oncologie Medicale.
  • Caen, France, 14076
    • Centre Francois Baclesse; Oncologie
  • Clermont Ferrand, France, 63011
    • Centre Jean Perrin
  • La Roche Sur Yon, France, 85025
    • CHD Vendée
  • Lille, France, 59000
    • Hopital Claude Huriez; Urologie
  • Montpellier, France, 34298
    • Institut régional du Cancer Montpellier
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Nimes, France, 30029
    • Institut de Cancérologie du Gard
  • Paris, France, 75674
    • Institut Mutualiste Montsouris; Oncologie
  • Poitiers, France, 86000
    • CHU Poitiers
  • Saint-Mande, France, 94160
    • Hopital d'Instruction des Armees de Begin
  • Suresnes, France, 92151
    • Hopital Foch; Oncologie
  • Villejuif, France, 94805
    • Institut Gustave Roussy; Departement Oncologie Medicale
• Greece
  • Athens, Greece, 155 62
    • IASO General Hospital of Athens
  • Athens, Greece, 115 28
    • Alexandras Hospital; Dept. of Clin. Therapeutics, Athens Uni School of Medicine
  • Patras, Greece, 265 04
    • University Hospital of Patras Medical Oncology
  • Thessaloniki, Greece, 564 29
    • Papageorgiou General Hospital; Medical Oncology
• Hungary
  • Budapest, Hungary, 1082
    • Semmelwies University of Medicine; Urology Dept.
  • Budapest, Hungary, 1122
    • Orszagos Onkologiai Intezet; "C" Belgyógyászati-Onkológiai és Klinikai Farmakológiai Osztály
  • Budapest, Hungary, 1145
    • Budapesti Uzsoki Utcai Kórház
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont ; Department of Oncology
  • Miskolc, Hungary, 3526
    • B-A-Z County Hospital
• Ireland
  • Cork, Ireland
    • Cork University Hospital
  • Dublin, Ireland, 7
    • Mater Misericordiae Uni Hospital; Oncology
  • Dublin, Ireland, 7
    • Mater Private Hospital
  • Dublin, Ireland, D24 NR0A
    • Adelaide & Meath Hospital, Dublin, Incorporating the National Children's Hospital; Oncology Day Unit
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus; Oncology
  • Kfar-Saba, Israel, 4428164
    • Meir Medical Center; Oncology
  • 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; Dipartimento Uro-Ginecologico
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • I.R.S.T Srl IRCCS; Oncologia Medica
    • Modena, Emilia-Romagna, Italy, 41124
      • A.O. Universitaria Policlinico Di Modena; Oncologia
  • Lazio
    • Roma, Lazio, Italy, 00152
      • Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica
  • Lombardia
    • Cremona, Lombardia, Italy, 26100
      • A.O. Istituti Ospitalieri - Cremona; S.C. Oncologia
    • Milano, Lombardia, Italy, 20133
      • Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
    • Milano, Lombardia, Italy, 20153
      • A.O. San Carlo Borromeo; U.O.C. Oncologia
    • Rozzano, Lombardia, Italy, 20089
      • Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
  • Toscana
    • Arezzo, Toscana, Italy, 52100
      • Ospedale Area Aretina Nord; U.O.C. Oncologia
    • Firenze, Toscana, Italy, 50139
      • Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1
  • Trentino-Alto Adige
    • Trento, Trentino-Alto Adige, Italy, 38122
      • Ospedale di Trento-Presidio Ospedaliero Santa Chiara; Oncologia Medica
• 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, 105-8470
    • Toranomon Hospital
  • 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
  • Goyang-si, Korea, Republic of, 10408
    • National Cancer Center
  • Seongnam-si, Korea, Republic of, 463-707
    • 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)
    • Cdmx, Mexico CITY (federal District), Mexico, 03100
      • Health Pharma Professional Research
    • Mexico City, Mexico CITY (federal District), Mexico, 11850
      • Hospital Angeles Mocel
  • Sinaloa
    • Culiacan, Sinaloa, Mexico
      • Centro Medico Culiacan SA de CV; Consultorio Medico 303 B
  • Yucatan
    • Mérida, Yucatan, Mexico, 97070
      • Medical Care & Research
• Norway
  • Grålum, Norway, 1714
    • Sykehuset Østfold Kalnes; Onkologisk seksjon
  • Lørenskog, Norway, 1478
    • Akershus Universitetssykehus HF
• Poland
  • ?ód?, Poland, 93-513
    • Woj. Wielospec. Centrum Onkologii i Traumatologii
  • Opole, Poland, 45-061
    • SPZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarawskiego
  • Warszawa, Poland, 02-781
    • Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Klinika Nowotworow Ukladu Moczowego
  • Warszawa, Poland, 04-073
    • Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.
  • Wroc?aw, Poland, 53-413
    • Dolno?l?skie Centrum Onkologii, Pulmonologii i Hematologii
• Portugal
  • Coimbra, Portugal, 3000-075
    • HUC; Servico de Urologia e Transplantacao Renal
  • Lisboa, Portugal, 1649-035
    • Hospital de Santa Maria; Servico de Oncologia Medica
  • Porto, Portugal, 4200-072
    • IPO do Porto; Servico de Oncologia Medica
• Russian Federation
  • Altaj
    • Barnaul, Altaj, Russian Federation, 656052
      • 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; Urological Dept
    • Moscow, Moskovskaja Oblast, Russian Federation, 117997
      • Russian Scientific Center of Roentgenoradiology
    • Moscow, Moskovskaja Oblast, Russian Federation, 125248
      • P.A. Herzen Oncological Inst. ; Oncology
  • Niznij Novgorod
    • Nizhny Novgorod, Niznij Novgorod, Russian Federation, 603001
      • Privolzhsk Regional Medical Center
• Spain
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial; Servicio de Urología
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal; Servicio de Oncologia
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos; Servicio de Oncologia
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre; Servicio de Oncologia
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
  • Malaga, Spain, 29010
    • Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio; Servicio de Oncologia
  • 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, 8208
      • Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
  • Cordoba
    • Córdoba, Cordoba, Spain, 14004
      • Hospital Universitario Reina Sofia; Servicio de Oncologia
  • Islas Baleares
    • Palma De Mallorca, Islas Baleares, Spain, 07014
      • Hospital Universitario Son Espases; Servicio de Oncologia
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria de Navarra; Servicio de Oncologia
• Taiwan
  • Kaohsiung, Taiwan, 807
    • KAOHSIUNG MEDICAL UNI CHUNG-HO HOSPITAL; Dept. Of Urology
  • Taichung, Taiwan, 40447
    • China Medical University Hospital; Urology
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital; Division of Urology
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital-LinKou; Urology
• Thailand
  • Bangkok, Thailand, 10330
    • Chulalongkorn Hospital; Medical Oncology
  • Bangkok, Thailand, 10700
    • Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc
  • Chiangmai, Thailand, 50200
    • Maharaj Nakorn Chiangmai Hospital; Department of Surgery/ Urology unit
• United Kingdom
  • Blackburn, United Kingdom, BB2 3HH
    • Royal Blackburn Hospital
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrookes Nhs Trust; Oncology Clinical Trials Unit
  • 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; Dept. of Clinical Oncology
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital; Institute of Cancer Research
  • Wolverhampton, United Kingdom, WV10 0QP
    • Royal Wolverhampton hospital; McHale Building
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Ironwood Cancer & Research Centers
    • Scottsdale, Arizona, United States, 85025
      • Mayo Clinic Arizona
  • California
    • Beverly Hills, California, United States, 90211
      • USC/Westside Cancer Ctr
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90033
      • USC Norris Cancer Center
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente San Diego - Los Angeles
    • 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; John Theurer Cancer Ctr
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Cleveland Clinic
  • Oregon
    • Tigard, Oregon, United States, 97223
      • 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, 84112
      • 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 PCWG3 Criteria (PTEN Loss Population)	Radiographic progression-free survival is defined as time from date of randomization to the first occurrence of documented disease progression, as assessed by the investigator with use of the Prostate Cancer Working Group 3 (PCWG3) criteria or death from any cause, whichever occurs first. Disease progression for soft tissue is 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, and an absolute increase of at least 5 mm in the sum of diameters of target lesions; progression of non target lesions; the appearance of one or more new lesions. Disease progression for bone lesions is defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later. rPFS will be analyzed in participants with phosphatase and tensin homolog (PTEN) - loss tumors (using the Ventana PTEN immunohistochemistry (IHC) assay).	Up to approximately 31 months
Investigator-Assessed Radiographic Progression-Free Survival (rPFS) Per PCWG3 Criteria (Intent-To-Treat (ITT) Population)	Radiographic progression-free survival is defined as time from date of randomization to the first occurrence of documented disease progression, as assessed by the investigator with use of the Prostate Cancer Working Group 3 (PCWG3) criteria or death from any cause, whichever occurs first. Disease progression for soft tissue is 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, and an absolute increase of at least 5 mm in the sum of diameters of target lesions; progression of non target lesions; the appearance of one or more new lesions. Disease progression for bone lesions is defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later. rPFS will be analyzed in the Intent-to-Treat (ITT) population.	Up to approximately 31 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall Survival (OS) is defined as the time from randomization to death due to any cause. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.	Up to approximately 7 years
Time to Pain Progression	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 are asymptomatic at baseline or pain worsening for those who are mildly symptomatic at baseline. Pain severity will be graded on a 10-point scale, with 0=no pain and 10=severe pain. Pain severity progression is defined as a ≥ 2-point absolute increase from baseline. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.	Up to approximately 7 years
Time to Initiation of Cytotoxic Chemotherapy	Time to initiation of cytotoxic chemotherapy is 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 prostate cancer. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.	Up to approximately 7 years
Time to Function Deterioration	Time to function deterioration was defined as the time from the date of randomisation to the date of 10-point or more decrease on either the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) PF (Physical Functioning) or RF (Role Functioning) scale scores (range, 0-100) held for two consecutive assessments, or a 10 point or more score decrease followed by death (any cause) within 28 days, whichever occurs first. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.	Up to approximately 7 years
Time to Prostate-Specific Antigen (PSA) Progression	Time to PSA progression is defined as the time from the date of randomization to the first occurrence of PSA progression, per the PCWG3 criteria. PSA progression is defined as a PSA increase that is ≥ 25% and ≥ 2 ng/mL above the baseline or the nadir, which is confirmed by a second value ≥ 3 weeks later. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.	Up to approximately 7 years
Time to First Opioid Use	Time to first opioid use is defined as the documentation of the first opioid prescription for cancer-related pain followed by the participant's record of opioid intake or availability of an Analgesic Quantification Algorithm (AQA) daily score. Participants reporting use of opioid for cancer-related pain at baseline will be excluded from the analysis. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.	Up to approximately 7 years
Time to Symptomatic Skeletal Event (SSE)	Time to SSE is defined as the time interval from the date of randomization to the date of an SSE. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.	Up to approximately 7 years
Objective Response Rate (ORR)	An objective response is 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. Participants without a post-baseline tumor assessment will be considered non-responders. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.	Up to approximately 7 years
PSA Response Rate	PSA response rate is defined as the percentage of participants achieving a PSA decline ≥50% from baseline. Participants without a post-baseline PSA assessment will be considered non-responders. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.	Up to approximately 7 years
Investigator-Assessed rPFS Per PCWG3 Criteria in Participants With PTEN-Loss Tumors by Next-Generation Sequencing (NGS)	Investigator-assessed rPFS is defined as time from date of randomization to the first occurrence of documented disease progression, as assessed by the investigator with use of the Prostate Cancer Working Group 3 (PCWG3) criteria or death from any cause, whichever occurs first and will be analyzed in participants with PTEN-loss tumors by NGS. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.	Up to approximately 7 years
Duration of Response (DOR)	Duration of Response (DOR) is defined as the time from first occurrence of a documented confirmed objective response until the time of documented disease progression as determined by the investigator using RECIST v1.1 and PCWG3 criteria, or death from any cause, whichever occurs first. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.	Up to approximately 7 years
Percentage of Participants With Adverse Events (AEs)	An Adverse Event (AE) is 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 Adverse Event 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 are also considered as Adverse Events. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.	Baseline up until 28 days after the last dose of study drug or initiation of subsequent lines of anti-cancer therapy, whichever occurs first (up to a maximum of 7 years).
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)

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 (Estimated): April 30, 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): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Metastatic Castrate-Resistant Prostate Cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protein Kinase Inhibitors; Prednisolone; Prednisone; 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