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

Metastatic Prostate Cancer Clinical Trial

— IPATential150  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03072238
• Other study ID #: CO39303
• Secondary ID: 2016-004429-17
• Status: Completed
• Phase: Phase 3
• Start date: June 30, 2017
• Est. completion date: April 24, 2024

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1101
• Est. completion date: April 24, 2024
• Est. primary completion date: March 16, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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-a 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)

Related Conditions & MeSH terms

• Metastatic Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Ipatasertib
Oral tablets, 400 mg, given once daily (QD) beginning on Day 1 of Cycle 1 until disease progression or intolerable toxicity.
• Abiraterone
Oral tablets of abiraterone, 1000 mg QD, taken on an empty stomach and swallowed whole with water.
• Placebo
Oral tablets (matched to ipatasertib appearance), given QD beginning on Day 1 of Cycle 1 until disease progression or intolerable toxicity.
• Prednisone/Prednisolone
Oral tablets of 5 mg, taken twice daily (BID) until disease progression or intolerable toxicity.

Locations

Country	Name	City	State
Australia	Monash Medical Centre; Oncology	Clayton	Victoria
Australia	Adelaide Cancer Centre	Kurralta Park	South Australia
Australia	Macquarie University Hospital	Macquarie Park	New South Wales
Australia	Eastern Health; GU - Oncology	Melbourne	Victoria
Australia	Peter Maccallum Cancer Centre	Melbourne	Victoria
Austria	LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie	Graz
Austria	Ordensklinikum Linz Elisabethinen; Abteilung für Urologie und Andrologie	Linz
Austria	Landeskrankenhaus Salzburg; Universitätsklinik für Urologie und Andrologie der PMU	Salzburg
Belgium	UZ Gent	Gent
Belgium	AZ Groeninge	Kortrijk
Belgium	CHU Sart-Tilman	Liège
Brazil	Hospital Luxemburgo; Oncologia	Belo Horizonte	MG
Brazil	Liga Norte Riograndense Contra O Câncer	Natal	RN
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Canada	Hamilton Health Sciences - Juravinski Cancer Centre	Hamilton	Ontario
Canada	Hopital Sacre-Coeur Research Centre	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Lakeridge Health Oshawa; Oncology	Oshawa	Ontario
Canada	CHU de Québec - Université Laval - Hôtel-Dieu de Québec	Quebec
Canada	Princess Margaret Cancer Center	Toronto	Ontario
Canada	Sunnybrook Research Institute	Toronto	Ontario
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
China	Beijing Friendship Hospital Affiliated of Capital University of Medical Science	Beijing Shi
China	Jiangsu Cancer Hospital	Nanjing City
China	Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School	Nanjing City
China	Zhongshan Hospital Fudan University	Shanghai
China	Fudan University Shanghai Cancer Center	Shanghai City
China	First Affiliated Hospital of Medical College of Xi'an Jiaotong University	Xi'an
Costa Rica	Clinica CIMCA	San José
Costa Rica	ICIMED Instituto de Investigación en Ciencias Médicas	San José
Denmark	Aarhus Universitetshospital, Urologisk Afd. K	Aarhus N
Denmark	Odense Universitetshospital, Onkologisk Afdeling R	Odense C
France	ICO Paul Papin; Oncologie Medicale.	Angers
France	Centre Francois Baclesse; Oncologie	Caen
France	Centre Jean Perrin	Clermont Ferrand
France	CHD Vendée	La Roche Sur Yon
France	Hopital Claude Huriez; Urologie	Lille
France	Institut régional du Cancer Montpellier	Montpellier
France	Centre Antoine Lacassagne	Nice
France	Institut de cancerologie du Gard	Nimes
France	Institut Mutualiste Montsouris; Oncologie	Paris
France	CHU Poitiers	Poitiers
France	Hopital d'Instruction des Armees de Begin	Saint-Mande
France	Hopital Foch; Oncologie	Suresnes
France	Institut Gustave Roussy; Departement Oncologie Medicale	Villejuif
Greece	Alexandras Hospital; Dept. of Clin. Therapeutics, Athens Uni School of Medicine	Athens
Greece	IASO General Hospital of Athens	Athens
Greece	University Hospital of Patras Medical Oncology	Patras
Greece	Papageorgiou General Hospital; Medical Oncology	Thessaloniki
Hungary	Budapesti Uzsoki Utcai Kórház	Budapest
Hungary	Orszagos Onkologiai Intezet; "C" Belgyógyászati-Onkológiai és Klinikai Farmakológiai Osztály	Budapest
Hungary	Semmelwies University of Medicine; Urology Dept.	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont ; Department of Oncology	Debrecen
Hungary	B-A-Z County Hospital	Miskolc
Ireland	Cork University Hospital	Cork
Ireland	Adelaide & Meath Hospital, Dublin, Incorporating the National Children's Hospital; Oncology Day Unit	Dublin
Ireland	Mater Misericordiae Uni Hospital; Oncology	Dublin
Ireland	Mater Private Hospital	Dublin
Israel	Rambam Health Care Campus; Oncology	Haifa
Israel	Meir Medical Center; Oncology	Kfar-Saba
Israel	Belinson Medical Center, Division of Oncology	Petach Tikva
Israel	Chaim Sheba medical center, Oncology division	Ramat Gan
Italy	Ospedale Area Aretina Nord; U.O.C. Oncologia	Arezzo	Toscana
Italy	A.O. Istituti Ospitalieri - Cremona; S.C. Oncologia	Cremona	Lombardia
Italy	Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1	Firenze	Toscana
Italy	I.R.S.T Srl IRCCS; Oncologia Medica	Meldola	Emilia-Romagna
Italy	A.O. San Carlo Borromeo; U.O.C. Oncologia	Milano	Lombardia
Italy	Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2	Milano	Lombardia
Italy	A.O. Universitaria Policlinico Di Modena; Oncologia	Modena	Emilia-Romagna
Italy	ISTITUTO NAZIONALE TUMORI IRCCS FONDAZIONE G. PASCALE; Dipartimento Uro-Ginecologico	Napoli	Campania
Italy	Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica	Roma	Lazio
Italy	Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia	Rozzano	Lombardia
Italy	Ospedale di Trento-Presidio Ospedaliero Santa Chiara; Oncologia Medica	Trento	Trentino-Alto Adige
Japan	Nagoya University Hospital	Aichi
Japan	Hirosaki University Hospital	Aomori
Japan	National Cancer Center East	Chiba
Japan	Toho University Sakura Medical Center	Chiba
Japan	Gunma University Hospital	Gunma
Japan	National Hospital Organization Hokkaido Cancer Center	Hokkaido
Japan	Kanazawa University Hospital	Ishikawa
Japan	Kitasato University Hospital	Kanagawa
Japan	Yokohama City University Medical Center	Kanagawa
Japan	Kochi Medical School Hospital	Kochi
Japan	Kumamoto University Hospital	Kumamoto
Japan	University Hospital Kyoto Prefectural University of Medicine	Kyoto
Japan	Niigata University Medical & Dental Hospital	Niigata
Japan	Kindai University Hospital	Osaka
Japan	Keio University Hospital	Tokyo
Japan	Kyorin University Hospital	Tokyo
Japan	Nippon Medical School Hospital	Tokyo
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	Toranomon Hospital	Tokyo
Japan	Yamaguchi University Hospital	Yamaguchi
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Mexico	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)
Mexico	Centro Medico Culiacan SA de CV; Consultorio Medico 303 B	Culiacan	Sinaloa
Mexico	Consultorio de Especialidad en Urologia Privado	Durango
Mexico	Medical Care & Research	Mérida	Yucatan
Mexico	Hospital Angeles Mocel	Mexico City	Mexico CITY (federal District)
Norway	Sykehuset Østfold Kalnes; Onkologisk seksjon	Grålum
Norway	Akershus universitetssykehus HF	Lørenskog
Poland	Woj. Wielospec. Centrum Onkologii i Traumatologii	?ód?
Poland	SPZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarawskiego	Opole
Poland	Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Klinika Nowotworow Ukladu Moczowego	Warszawa
Poland	Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.	Warszawa
Poland	Dolno?l?skie Centrum Onkologii, Pulmonologii i Hematologii	Wroc?aw
Portugal	HUC; Servico de Urologia e Transplantacao Renal	Coimbra
Portugal	Hospital de Santa Maria; Servico de Oncologia Medica	Lisboa
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Russian Federation	Altai Regional Oncological Center	Barnaul	Altaj
Russian Federation	Moscow City Oncology Hospital #62	Moscovskaya Oblast	Moskovskaja Oblast
Russian Federation	Blokhin Cancer Research Center; Urological Dept	Moscow	Moskovskaja Oblast
Russian Federation	P.A. Herzen Oncological Inst. ; Oncology	Moscow	Moskovskaja Oblast
Russian Federation	Russian Scientific Center of Roentgenoradiology	Moscow	Moskovskaja Oblast
Russian Federation	Privolzhsk Regional Medical Center	Nizhny Novgorod	Niznij Novgorod
Spain	Institut Catala d?Oncologia Hospital Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Clinic i Provincial; Servicio de Urología	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia	Barcelona
Spain	Hospital Universitario Reina Sofia; Servicio de Oncologia	Córdoba	Cordoba
Spain	Insititut Catala D'Oncologia	Hospitalet de Llobregat	Barcelona
Spain	Hospital Clinico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid
Spain	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga
Spain	Hospital Universitario Son Espases; Servicio de Oncologia	Palma De Mallorca	Islas Baleares
Spain	Clinica Universitaria de Navarra; Servicio de Oncologia	Pamplona	Navarra
Spain	Corporacio Sanitaria Parc Tauli; Servicio de Oncologia	Sabadell	Barcelona
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Taiwan	KAOHSIUNG MEDICAL UNI CHUNG-HO HOSPITAL; Dept. Of Urology	Kaohsiung
Taiwan	China Medical University Hospital; Urology	Taichung
Taiwan	Taichung Veterans General Hospital; Division of Urology	Taichung
Taiwan	Chang Gung Memorial Hospital-LinKou; Urology	Taoyuan
Thailand	Chulalongkorn Hospital; Medical Oncology	Bangkok
Thailand	Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology	Bangkok
Thailand	Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc	Bangkok
Thailand	Maharaj Nakorn Chiangmai Hospital; Department of Surgery/ Urology unit	Chiangmai
United Kingdom	Royal Blackburn Hospital	Blackburn
United Kingdom	Addenbrookes Nhs Trust; Oncology Clinical Trials Unit	Cambridge
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Mount Vernon & Watford Trust Hospital; Dept. of Clinical Oncology	Northwood
United Kingdom	Royal Marsden Hospital; Institute of Cancer Research	Sutton
United Kingdom	Royal Wolverhampton hospital; McHale Building	Wolverhampton
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Northside Hospital	Atlanta	Georgia
United States	University of Colorado Hospital - Anschutz Cancer Pavilion	Aurora	Colorado
United States	USC/Westside Cancer Ctr	Beverly Hills	California
United States	Lynn Cancer Institute/Boca Raton Regional Hospital	Boca Raton	Florida
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Ironwood Cancer & Research Centers	Chandler	Arizona
United States	Charleston Oncology, P .A	Charleston	South Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	Karmanos Cancer Institute..	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Hackensack Univ Medical Center; John Theurer Cancer Ctr	Hackensack	New Jersey
United States	HCA Midwest Division	Kansas City	Missouri
United States	Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley	Las Vegas	Nevada
United States	Kaiser Permanente San Diego - Los Angeles	Los Angeles	California
United States	USC Norris Cancer Center	Los Angeles	California
United States	Miami Cancer Institute of Baptist Health, Inc.	Miami	Florida
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Yale Cancer Center	New Haven	Connecticut
United States	Urology Cancer Center & GU Research Network	Omaha	Nebraska
United States	UC Irvine Medical Center	Orange	California
United States	Stanford University	Palo Alto	California
United States	Illinois Cancer Care	Peoria	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Allegheny Cancer Center	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Associates in Oncology/Hematology P.C.	Rockville	Maryland
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Pacific Hematology Oncology Associates	San Francisco	California
United States	Mayo Clinic Arizona	Scottsdale	Arizona
United States	Texas Oncology - Gulf Coast	The Woodlands	Texas
United States	Northwest Cancer Specialists, P.C.	Tigard	Oregon
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Costa Rica,  Denmark,  France,  Greece,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Norway,  Poland,  Portugal,  Russian Federation,  Spain,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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).
Secondary	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)
Secondary	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)