Clinical trial NCT01485861: Study of Ipatasertib or Apitolisib With Abiraterone Acetate Versus Abiraterone Acetate in Participants With Castration-Resistant Prostate Cancer Previously Treated With Docetaxel Chemotherapy
Official title: A Phase Ib/II Study of Ipatasertib (GDC-0068) or Apitolisib (GDC-0980) With Abiraterone Acetate Versus Abiraterone Acetate in Patients With Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2011-12-06
Enrollment: 298
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This multicenter, international, Phase Ib/II trial consists of three stages: a Phase Ib, open-label stage in which the recommended Phase II dose was determined for ipataseritib administrated in combination with abiraterone and of apitolisib administrated in combination with abiraterone (this phase is no longer active), a Phase II, 3-arm, double-blind, randomized comparison of ipatasertib with abiraterone and prednisone/prednisolone versus placebo with abiraterone and prednisone/prednisolone and a safety single-arm, open-label cohort of ipatasertib 400 mg daily alone or in combination with prednisone/prednisolone or prednisone/prednisolone plus abiraterone.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed metastatic or advanced prostate adenocarcinoma that has been previously treated with docetaxel-based therapy and has progressed during treatment of at least one hormonal therapy(prior docetaxel is not required for the safety cohort)
* Two rising PSA levels greater than or equal to (\>/=) 2 ng/mL measured \>/= 1 week apart or radiographic evidence of disease progression in soft tissue or bone
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening
* Adequate hematologic and organ function
* Documented willingness to use an effective means of contraception
* Safety cohort only: agreement to use CGM for first cycle of treatment

Exclusion Criteria:

* History of Type I or Type II diabetes mellitus requiring insulin; safety cohort: patients who are receiving any pharmacologic treatment for diabetes are not eligible
* New York Heart Association Class III or IV heart failure or Left ventricular ejection fraction \< 50% or ventricular arrhythmia requiring medication
* Significant atherosclerotic disease, as evidenced by: unstable angina, history of myocardial infarction within 6 months prior to Day 1, or cerebrovascular accident within 6 months prior to Day 1
* Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs or active inflammatory disease which requires immunosuppressive therapy
* Clinically significant history of liver disease
* History of adrenal insufficiency or hyperaldosteronism
* Phase II only: Previous therapy for prostate cancer with 17 alpha-hydroxylase/C17,20-lyase inhibitors, including abiraterone
* Phase II only: Previous treatment for prostate cancer with Protein kinase B phosphatidylinositol 3 kinase and/or mammalian target of rapamycin inhibitors
* Need for chronic corticosteroid therapy of \>/= 20 mg of prednisone per day or an equivalent dose of other anti inflammatory corticosteroids or immunosuppressant

Primary outcomes:
measure: Phase Ib: Percentage of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: Days 1 to 28 of Cycle 1 (Cycle length = 28 days)
measure: Phase Ib: Percentage of Participants With Adverse Events (AEs)
timeFrame: Baseline up until 30 days following the last administration of study treatment or until initiation of another anti-cancer therapy, whichever occurs first (up to approximately 10 months).
measure: Phase Ib: Recommended Phase II Dose (RP2D) of Ipatasertib and Apitolisib
timeFrame: Days 1 to 28 of Cycle 1 (Cycle length = 28 days)
measure: Phase II: Radiographic Progression Free Survival (rPFS) (Intent-To-Treat [ITT] Population)
timeFrame: Screening up to radiographic progression or death, whichever occurred first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days)
measure: Phase II: rPFS in Participants With Institute of Cancer Research (ICR) Phosphatase and Tensin Homolog (PTEN) Loss
timeFrame: Screening up to radiographic progression or death, whichever occurred first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days)
Secondary outcomes:
measure: Phase Ib: Maximum Plasma Concentration (Cmax) of Ipatasertib When Co-Administered With Abiraterone
timeFrame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
measure: Phase Ib: Time to Cmax (Tmax) of Ipatasertib When Co-Administered With Abiraterone
timeFrame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
measure: Phase Ib: Area Under The Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) of Ipatasertib When Co-Administered With Abiraterone
timeFrame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
measure: Phase Ib: Total Body Clearance (CL/F) of Ipatasertib When Co-Administered With Abiraterone
timeFrame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 15 of Cycle 1 (cycle length = 28 days)
measure: Phase Ib: Accumulation Ratio of Ipatasertib When Co-Administered With Abiraterone
timeFrame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
measure: Phase Ib: Cmax of G-037720 (Metabolite of Ipatasertib)
timeFrame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
measure: Phase Ib: Tmax of G-037720 (Metabolite of Ipatasertib)
timeFrame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
measure: Phase Ib: AUC0-24 of G-037720 (Metabolite of Ipatasertib)
timeFrame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
measure: Phase Ib: Accumulation Ratio of G-037720 (Metabolite of Ipatasertib)
timeFrame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
measure: Phase Ib: Cmax of Apitolisib When Co-Administered With Abiraterone
timeFrame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
measure: Phase Ib: Tmax of Apitolisib When Co-Administered With Abiraterone
timeFrame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
measure: Phase Ib: AUC0-24 of Apitolisib When Co-Administered With Abiraterone
timeFrame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
measure: Phase Ib: Cmax of Abiraterone When Co-Administered With Ipatasertib or Apitolisib
timeFrame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
measure: Phase Ib: Tmax of Abiraterone When Co-Administered With Ipatasertib or Apitolisib
timeFrame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
measure: Phase Ib: AUC0-24 of Abiraterone When Co-Administered With Ipatasertib or Apitolisib
timeFrame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
measure: Phase Ib: Plasma Half-Life of Abiraterone When Co-Administered With Ipatasertib or Apitolisib
timeFrame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
measure: Phase Ib: Accumulation Ratio of Abiraterone When Co-Administered With Ipatasertib or Apitolisib
timeFrame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
measure: Phase II: Overall Survival (ITT Population)
timeFrame: Screening up to death (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 8.9 years overall]) (cycle length = 28 days)
measure: Phase II: Overall Survival in Participants With ICR IHC PTEN Loss
timeFrame: Screening up to death (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 8.9 years overall]) (cycle length = 28 days)
measure: Phase II: Percentage of Participants With PSA Progression (ITT Population)
timeFrame: Screening up to PSA progression (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days)
measure: Phase II: Percentage of Participants With PSA Progression in Participants With ICR PTEN Loss
timeFrame: Screening up to PSA progression (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days)
measure: Phase II: Time to PSA Progression (ITT Population)
timeFrame: Screening up to PSA progression (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days)
measure: Phase II: Time to PSA Progression in Participants With ICR PTEN Loss
timeFrame: Screening up to PSA progression (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days)
measure: Phase II: Percentage of Participants With PSA Response (ITT Population)
timeFrame: Baseline up to 30 days after last dose (assessed at baseline, Day 1 of every cycle [starting from Cycle 2] till 30 days after last dose [up to overall 3.6 years]) (cycle length = 28 days)
measure: Phase II: Percentage of Participants With PSA Response in Participants With ICR PTEN Loss
timeFrame: Baseline up to 30 days after last dose (assessed at baseline, Day 1 of every cycle [starting from Cycle 2] till 30 days after last dose [up to overall 3.6 years]) (cycle length = 28 days)
measure: Phase II: Percentage of Participants With Objective Response (ITT Population)
timeFrame: Screening up to radiographic progression or death, whichever occurred first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days)
measure: Phase II: Percentage of Participants With Objective Response in Participants With ICR PTEN Loss
timeFrame: Screening up to radiographic progression or death, whichever occurred first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days)
measure: Phase II: Duration of Tumor Response (ITT Population)
timeFrame: Screening up to radiographic progression or death, whichever occurred first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days)
measure: Phase II: Duration of Tumor Response in Participants With ICR PTEN Loss
timeFrame: Screening up to radiographic progression or death, whichever occurred first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days)
measure: Phase II: Percentage of Participants With Circulating Tumor Cells (CTC) Reduction Response (ITT Population)
timeFrame: Baseline, on Day 1 of Cycle 2, on Day 1 of Cycle 3, and at the treatment completion visit (up to overall 3.6 years) (cycle length=28 days)
measure: Phase II: Percentage of Participants With CTC Reduction Response in Participants With ICR PTEN Loss
timeFrame: Baseline, on Day 1 of Cycle 2, on Day 1 of Cycle 3, and at the treatment completion visit (up to overall 3.6 years) (cycle length=28 days)
measure: Phase II: Percentage of Participants With CTC Conversion (ITT Population)
timeFrame: Baseline, on Day 1 of Cycle 2, on Day 1 of Cycle 3, and at the treatment completion visit (up to overall 3.6 years) (cycle length=28 days)
measure: Phase II: Percentage of Participants With CTC Conversion in Participants With ICR PTEN Loss
timeFrame: Baseline, on Day 1 of Cycle 2, on Day 1 of Cycle 3, and at the treatment completion visit (up to overall 3.6 years) (cycle length=28 days)
measure: Phase II: Percentage of Participants With Pain Progression (ITT Population)
timeFrame: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years)
measure: Phase II: Percentage of Participants With Pain Progression in Participants With ICR PTEN Loss
timeFrame: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years)
measure: Phase II: Time to Pain Progression (ITT Population)
timeFrame: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years)
measure: Phase II: Time to Pain Progression in Participants With ICR PTEN Loss
timeFrame: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years)
measure: Phase II: Percentage of Participants With Adverse Events (AEs)
timeFrame: Baseline up until 30 days following the last administration of study treatment or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 8.9 years)
measure: Phase II: Ipatasertib Plasma Concentrations When Co-Administered With Abiraterone
timeFrame: Phase II: Cycle 1, Day 1: 1, 4 hours postdose; Cycle 1, Day 15: predose, 2, 4 hours postdose; Cycle 2, Day 1: predose, 1-4 hours postdose (cycle length = 28 days)
measure: Phase II: G-037720 (Metabolite of Ipatasertib) Plasma Concentrations
timeFrame: Phase II: Cycle 1, Day 1: 1, 4 hours postdose; Cycle 1, Day 15: predose, 2, 4 hours postdose; Cycle 2, Day 1: predose, 1-4 hours postdose (cycle length = 28 days)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute ? Bisgrove
state: Arizona
city: San Francisco
country: United States
facility: Pacific Hematology Oncology Associates
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - Fort Myers (New Hampshire Ct)
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists; Sarasota
state: Florida
city: Honolulu
country: United States
facility: Kaiser Permanente Medical Ctr
state: Hawaii
city: Baltimore
country: United States
facility: Johns Hopkins Univ; Bunting Blaustein Cancer Center
state: Maryland
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Omaha
country: United States
facility: Urology Cancer Center & GU Research Network
state: Nebraska
city: East Setauket
country: United States
facility: New York Cancer and Blood Specialists - Setauket Medical Oncology
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center - Tennessee Oncology, Pllc
state: Tennessee
city: Brno
country: Czechia
facility: Masarykuv onkologicky ustav
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove; I. interni klinika,Oddeleni invazivni kardiologie
city: Praha 2
country: Czechia
facility: Urocentrum Praha s.r.o.
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Praha
country: Czechia
facility: Fakultni Thomayerova Nemocnice; Revmatologicke Oddeleni
city: Angers
country: France
facility: ICO Paul Papin; Oncologie Medicale.
city: Lyon
country: France
facility: Centre Léon Bérard - Centre régional de lutte contre le cancer Rhône-Alpes
city: Paris
country: France
facility: Hia Du Val De Grace
city: Paris
country: France
facility: Institut Curie; Oncologie Medicale
city: Paris
country: France
facility: GH Paris Saint Joseph; Hopital De Jour Oncologie
city: Saint-Mande
country: France
facility: Hopital d'Instruction des Armees de Begin
city: Villejuif
country: France
facility: Institut Gustave Roussy; Departement Oncologie Medicale
city: Athens
country: Greece
facility: Alexandras Hospital; Dept. of Clin. Therapeutics, Athens Uni School of Medicine
city: Heraklion
country: Greece
facility: Univ General Hosp Heraklion; Medical Oncology
city: Larissa
country: Greece
facility: University Hospital of Larissa; Oncology
city: Patras
country: Greece
facility: University Hospital of Patras Medical Oncology
city: Piraeus
country: Greece
facility: Metropolitan Hospital; 2Nd Oncology Clinic
city: Meldola
country: Italy
facility: IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
state: Emilia-Romagna
city: Cremona
country: Italy
facility: Azienda Ospedaliera Istituti Ospitalieri
state: Lombardia
city: Milano
country: Italy
facility: Irccs Ospedale San Raffaele;Oncologia Medica
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
state: Lombardia
city: Arezzo
country: Italy
facility: Ospedale S. Donato; Divisione Di Reumatologia
state: Toscana
city: Amsterdam
country: Netherlands
facility: Het Nederlands Kanker Inst
city: Amsterdam
country: Netherlands
facility: Vu Medisch Centrum; Afdeling Longziekten
city: Den Haag
country: Netherlands
facility: MC Haaglanden; Oncologie
city: Nijmegen
country: Netherlands
facility: UMC St Radboud
city: Rotterdam
country: Netherlands
facility: Sint Franciscus Gasthuis; Inwendige Geneeskunde
city: Brasov
country: Romania
facility: Sf. Constantin Hospital; Oncology
city: Bucharest
country: Romania
facility: Prof. Dr. Th. Burghele Clin Urology Hosp
city: Cluj Napoca
country: Romania
facility: Prof. Dr. I. Chiricuta Institute of Oncology
city: Timisoara
country: Romania
facility: ONCOMED - Medical Centre
city: Turda
country: Romania
facility: Municipal Hosp Turdal; Oncology
city: Elche
country: Spain
facility: Hospital General Universitario de Elche; Servicio de Oncologia
state: Alicante
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
state: Barcelona
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
state: Barcelona
city: Sant Andreu de La Barca
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
state: Barcelona
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Madrid Norte Sanchinarro
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital; Centre for Clinical Haematology
city: Glasgow
country: United Kingdom
facility: Gartnavel General Hospital
city: Leeds
country: United Kingdom
facility: St. James University Hospital; Pharmacy Department
city: Liverpool
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: