Prostate CancerPhase 1/2NCT01485861
Study of Ipatasertib or Apitolisib With Abiraterone Acetate Versus Abiraterone Acetate in Participants With Castration-Resistant Prostate Cancer Previously Treated With Docetaxel Chemotherapy
A Phase 1/2 study testing Abiraterone, Apitolisib and Ipatasertib in people with Prostate Cancer, run by Genentech, Inc. at 59 sites in 9 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Abiraterone, Apitolisib and Ipatasertib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 298 participants
- Where
- 59 sitesin 9 countries
- Study dates
- 11 Jan 2012to 31 Aug 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
59 sites in 9 countries.
59 sites in 9 countries
United States12 sites
Johns Hopkins Univ; Bunting Blaustein Cancer Center
Baltimore, Maryland, 21231
Karmanos Cancer Institute
Detroit, Michigan, 48201
New York Cancer and Blood Specialists - Setauket Medical Oncology
East Setauket, New York, 11733
Florida Cancer Specialists - Fort Myers (New Hampshire Ct)
Fort Myers, Florida, 33901-8101
Kaiser Permanente Medical Ctr
Honolulu, Hawaii, 96819
Carolina Urologic Research Center
Myrtle Beach, South Carolina, 29572
Sarah Cannon Cancer Center - Tennessee Oncology, Pllc
Nashville, Tennessee, 37203
Weill Cornell Medical College
New York, New York, 10065
Urology Cancer Center & GU Research Network
Omaha, Nebraska, 68130
Pacific Hematology Oncology Associates
San Francisco, California, 94115
Florida Cancer Specialists; Sarasota
Sarasota, Florida, 34232
HonorHealth Research Institute ? Bisgrove
Scottsdale, Arizona, 85258
Spain9 sites
Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
Badalona, Barcelona, 08916
Hospital General Universitario de Elche; Servicio de Oncologia
Elche, Alicante, 03203
Hospital General Universitario Gregorio Marañon
Madrid, 28007
Hospital Universitario 12 de Octubre; Servicio de Oncologia
Madrid, 28041
Hospital Madrid Norte Sanchinarro
Madrid, 28050
Hospital Clinico Universitario Virgen de la Victoria
Málaga, 29010
Clinica Universitaria de Navarra
Pamplona, Navarre, 31008
Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
Sabadell, Barcelona, 8208
Hospital Univ Vall d'Hebron; Servicio de Oncologia
Sant Andreu de la Barca, Barcelona, 08740
France7 sites
ICO Paul Papin; Oncologie Medicale.
Angers, 49055
Centre Léon Bérard - Centre régional de lutte contre le cancer Rhône-Alpes
Lyon, 69008
Hia Du Val De Grace
Paris, 75230
Institut Curie; Oncologie Medicale
Paris, 75231
GH Paris Saint Joseph; Hopital De Jour Oncologie
Paris, 75674
Hopital d'Instruction des Armees de Begin
Saint-Mandé, 94160
Institut Gustave Roussy; Departement Oncologie Medicale
Villejuif, 94805
United Kingdom6 sites
Queen Elizabeth Hospital; Centre for Clinical Haematology
Birmingham, B15 2TH
Gartnavel General Hospital
Glasgow, G12 0XH
St. James University Hospital; Pharmacy Department
Leeds, LS9 7TF
The Clatterbridge Cancer Centre NHS Foundation Trust
Liverpool, L7 8YA
Sarah Cannon Research Institute
London, W1G 6AD
The Royal Marsden Hospital
Sutton, SM2 5PT
Czechia5 sites
Masarykuv onkologicky ustav
Brno, 656 53
Fakultni nemocnice Hradec Kralove; I. interni klinika,Oddeleni invazivni kardiologie
Hradec Králové, 50012
Urocentrum Praha s.r.o.
Prague, 120 00
Vseobecna fakultni nemocnice v Praze
Prague, 128 08
Fakultni Thomayerova Nemocnice; Revmatologicke Oddeleni
Prague, 140 59
Greece5 sites
Alexandras Hospital; Dept. of Clin. Therapeutics, Athens Uni School of Medicine
Athens, 115 28
Univ General Hosp Heraklion; Medical Oncology
Heraklion, 711 10
University Hospital of Larissa; Oncology
Larissa, 413 35
University Hospital of Patras Medical Oncology
Pátrai, 265 04
Metropolitan Hospital; 2Nd Oncology Clinic
Piraeus, 185 47
Italy5 sites
Ospedale S. Donato; Divisione Di Reumatologia
Arezzo, Tuscany, 52100
Azienda Ospedaliera Istituti Ospitalieri
Cremona, Lombardy, 26100
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
Meldola, Emilia-Romagna, 47014
Irccs Ospedale San Raffaele;Oncologia Medica
Milan, Lombardy, 20132
Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
Milan, Lombardy, 20133
Netherlands5 sites
Het Nederlands Kanker Inst
Amsterdam, 1066 EC
Vu Medisch Centrum; Afdeling Longziekten
Amsterdam, 1081 HV
UMC St Radboud
Nijmegen, 6525 GA
Sint Franciscus Gasthuis; Inwendige Geneeskunde
Rotterdam, 3045 PM
MC Haaglanden; Oncologie
The Hague, 2512 VA
Romania5 sites
Sf. Constantin Hospital; Oncology
Brasov, 500019
Prof. Dr. Th. Burghele Clin Urology Hosp
Bucharest, 050659
Prof. Dr. I. Chiricuta Institute of Oncology
Cluj-Napoca, 400015
ONCOMED - Medical Centre
Timișoara, 300239
Municipal Hosp Turdal; Oncology
Turda, 401103
About this study
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
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.
- Conditions
- Prostate Cancer
- Being tested
- Abiraterone, Apitolisib, Ipatasertib, Placebo, Prednisone
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AbirateroneDrug
Orally once daily
ApitolisibDrug
Orally once daily
IpatasertibDrug
Orally once daily
PlaceboDrug
Orally once daily
PrednisoneDrug
Orally bid
PrednisoloneDrug
Orally bid
| Study group | Role | What they receive |
|---|---|---|
| Phase Ib: Ipatasertib 400 mg + abiraterone | Experimental | Participants will receive ipatasertib 400 mg once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg twice daily (bid) continuously in 28-day treatment cycles until disease progression or intolerable toxicity. Receives: Drug: Abiraterone; Drug: Ipatasertib; Drug: Prednisone; Drug: Prednisolone |
| Phase Ib: Apitolisib 30 mg + abiraterone | Experimental | Participants will receive apitolisib 30 mg once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg twice daily (bid) continuously in 28-day treatment cycles until disease progression or intolerable toxicity. Receives: Drug: Abiraterone; Drug: Apitolisib; Drug: Prednisone; Drug: Prednisolone |
| Phase II: Ipatasertib 400 mg + abiraterone | Experimental | Participants will receive Ipatasertib 400 mg once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg bid continuously in 28-day treatment cycles until disease progression or intolerable toxicity. Receives: Drug: Abiraterone; Drug: Ipatasertib; Drug: Prednisone; Drug: Prednisolone |
| Phase II: Ipatasertib 200 mg + abiraterone | Experimental | Participants will receive Ipatasertib 200 mg once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg bid continuously in 28-day treatment cycles until disease progression or intolerable toxicity. Receives: Drug: Abiraterone; Drug: Ipatasertib; Drug: Prednisone; Drug: Prednisolone |
| Phase II: Placebo + abiraterone | Placebo comparator | Participants will receive placebo (for Ipatasertib) once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg bid continuously in 28-day treatment cycles until disease progression or intolerable toxicity. Receives: Drug: Abiraterone; Drug: Placebo; Drug: Prednisone; Drug: Prednisolone |
| Safety Cohort: Ipataseritib 400 mg + Abiraterone + Prednisone | Experimental | Participants will receive ipatasertib 400 mg orally once daily and/or prednisone/prednisolone 5 mg orally once daily or bid and/or abiraterone 1000 mg orally once daily according to the following schedule: ipatasertib in the morning during Cycle 1, Days 1-7; ipatasertib in the morning plus prednisone/prednisolone once at night during Cycle 1, Day 8; ipatasertib in the morning plus prednisone/prednisolone bid (morning and night) during Cycle 1, Days 9-11; ipatasertib in the morning plus prednisone/prednisolone bid (morning and night) and abiraterone in the morning during Cycle 1, Days 12-18; ipatasertib in the evening plus prednisone/prednisolone bid (morning and night) and abiraterone at the same time as ipatasertib during Cycle 1, Days 19-25; Cycle 2 and beyond ipatasertib once daily in the morning or evening, abiraterone at the same time as ipatasertib, and prednisone/prednisolone bid. Receives: Drug: Abiraterone; Drug: Ipatasertib; Drug: Prednisone; Drug: Prednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase Ib: Percentage of Participants With Dose-Limiting Toxicities (DLTs)
DLT: 1 of the following toxicities, at least possibly related to ipatasertib or apitolisib. 1) Grade ≥ 3 non-hematologic, non-hepatic major organ AE; 2) Grade ≥ 3 febrile neutropenia; 3) Grade ≥ 4 neutropenia (absolute neutrophils less than [<] 500 per microliter) lasting greater than (>) 7 days; 4) Grade ≥3 thrombocytopenia associated with acute hemorrhage; 5) Grade ≥4 thrombocytopenia; 6) Grade ≥4 anemia; 7) 1 episode of fasting Grade ≥4 hyperglycemia or 3 episodes of fasting Grade 3 hyperglycemia on separate days within 7 days, as determined by laboratory blood glucose evaluation; 8) Grade ≥3 elevation lasting for > 48 hours for hepatic transaminase or liver-specific alkaline phosphatase or total bilirubin. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v 4.0.
Measured: Days 1 to 28 of Cycle 1 (Cycle length = 28 days)
Phase Ib: Percentage of Participants With Adverse Events (AEs)
An Adverse Event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Measured: 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).
Phase Ib: Recommended Phase II Dose (RP2D) of Ipatasertib and Apitolisib
RP2D is a dose of a drug which would be used in Phase II stage of the study. RP2D was to be determined based on maximum tolerated dose (MTD) in Phase Ib stage of the study. The highest dose level (in 3+3 escalation scheme) with an acceptable safety profile and with a minimum of 6 participants at which fewer than one-third of participants experienced a DLT was declared the MTD and RP2D.
Measured: Days 1 to 28 of Cycle 1 (Cycle length = 28 days)
Phase II: Radiographic Progression Free Survival (rPFS) (Intent-To-Treat [ITT] Population)
rPFS: Time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments via CT scan and bone scans, or death on study from any cause, whichever occurred first. Progression was defined as follows: Soft tissue mass (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1): at least 20% increase in sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Bone: ≥ 2 new bone lesions plus 2 additional at confirmation on a second bone scan ≥ 4 weeks later (< 12 weeks after randomization). ≥ 2 new bone lesions consistent with progression, without need for confirmatory bone scan (≥ 12 weeks after randomization).
Measured: 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)
Phase II: rPFS in Participants With Institute of Cancer Research (ICR) Phosphatase and Tensin Homolog (PTEN) Loss
rPFS: Time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments via CT scan and bone scans, or death on study from any cause, whichever occurred first. Progression was defined as follows: Soft tissue mass (RECIST 1.1): at least 20% increase in sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Bone: ≥ 2 new bone lesions plus 2 additional at confirmation on 2nd bone scan ≥ 4 weeks later (< 12 weeks after randomization). ≥ 2 new bone lesions consistent with progression, without need for confirmatory bone scan (≥ 12 weeks after randomization). PTEN status was assessed by RUO IHC assay that was performed at ICR, UK. Samples with 100% of the tumor with no PTEN staining were classified as "ICR PTEN loss". Number of participants analyzed=participants with PTEN loss.
Measured: 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 (40)
Phase Ib: Maximum Plasma Concentration (Cmax) of Ipatasertib When Co-Administered With Abiraterone
Measured: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Time to Cmax (Tmax) of Ipatasertib When Co-Administered With Abiraterone
Measured: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Area Under The Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) of Ipatasertib When Co-Administered With Abiraterone
Measured: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Total Body Clearance (CL/F) of Ipatasertib When Co-Administered With Abiraterone
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Measured: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Accumulation Ratio of Ipatasertib When Co-Administered With Abiraterone
Accumulation Ratio was calculated as AUC0-24 (Cycle 1 Day 15) divided by AUC0-24 (Cycle 1 Day 1).
Measured: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Cmax of G-037720 (Metabolite of Ipatasertib)
G-037220 is N-dealkylated metabolite of ipatasertib and the main metabolite in circulation.
Measured: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Tmax of G-037720 (Metabolite of Ipatasertib)
G-037220 is N-dealkylated metabolite of ipatasertib and the main metabolite in circulation.
Measured: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: AUC0-24 of G-037720 (Metabolite of Ipatasertib)
G-037220 is N-dealkylated metabolite of ipatasertib and the main metabolite in circulation.
Measured: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Accumulation Ratio of G-037720 (Metabolite of Ipatasertib)
G-037220 is N-dealkylated metabolite of ipatasertib and the main metabolite in circulation. Accumulation Ratio was calculated as AUC0-24 (Cycle 1 Day 15) divided by AUC0-24 (Cycle 1 Day 1).
Measured: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Cmax of Apitolisib When Co-Administered With Abiraterone
Measured: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Tmax of Apitolisib When Co-Administered With Abiraterone
Measured: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: AUC0-24 of Apitolisib When Co-Administered With Abiraterone
Measured: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Cmax of Abiraterone When Co-Administered With Ipatasertib or Apitolisib
Measured: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Tmax of Abiraterone When Co-Administered With Ipatasertib or Apitolisib
Measured: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: AUC0-24 of Abiraterone When Co-Administered With Ipatasertib or Apitolisib
Measured: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Plasma Half-Life of Abiraterone When Co-Administered With Ipatasertib or Apitolisib
Measured: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Accumulation Ratio of Abiraterone When Co-Administered With Ipatasertib or Apitolisib
Accumulation Ratio was caculated as AUC0-24 (Cycle 1 Day 15) divided by AUC0-24 (Cycle 1 Day 1).
Measured: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase II: Overall Survival (ITT Population)
Overall survival was defined as the interval between the date of screening and death due to any cause. Overall survival was estimated using Kaplan Meier method.
Measured: 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)
Phase II: Overall Survival in Participants With ICR IHC PTEN Loss
Overall survival was defined as the interval between the date of randomization and death from any cause. Overall survival was estimated using Kaplan Meier method. PTEN status was assessed by RUO IHC assay that was performed at ICR, UK. Samples with 100% of the tumor with no PTEN staining were classified as "ICR PTEN loss".
Measured: 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)
Phase II: Percentage of Participants With PSA Progression (ITT Population)
PSA progression was defined as per Prostate Cancer Working Group 2 criteria. PSA progression was defined as a ≥ 25% increase and an absolute increase of ≥ 2 nanogram per milliliter (ng/mL) from the baseline value, or a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL from the nadir if PSA decreases from baseline after treatment, which was confirmed by a second value obtained ≥ 3 weeks later.
Measured: 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)
Phase II: Percentage of Participants With PSA Progression in Participants With ICR PTEN Loss
PSA progression was defined as per Prostate Cancer Working Group 2 criteria. PSA progression was defined as a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL from the baseline value, or a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL from the nadir if PSA decreases from baseline after treatment, which was confirmed by a second value obtained ≥ 3 weeks later. PTEN status was assessed by RUO IHC assay that was performed at ICR, UK. Samples with 100% of the tumor with no PTEN staining were classified as "ICR PTEN loss".
Measured: 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)
Phase II: Time to PSA Progression (ITT Population)
Time to PSA progression: Time from screening to the first occurrence of PSA progression, as determined by investigator. PSA progression was defined as per Prostate Cancer Working Group 2 criteria. PSA progression is defined as a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL from the baseline value, or a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL from the nadir if PSA decreases from baseline after treatment, which was confirmed by a second value obtained ≥ 3 weeks later.
Measured: 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)
Phase II: Time to PSA Progression in Participants With ICR PTEN Loss
Time to PSA progression: Time from screening to the first occurrence of PSA progression, as determined by investigator. PSA progression was defined as per Prostate Cancer Working Group 2 criteria. PSA progression was defined as a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL from the baseline value, or a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL from the nadir if PSA decreases from baseline after treatment, which was confirmed by a second value obtained ≥ 3 weeks later. PTEN status was assessed by RUO IHC assay that was performed at ICR, UK. Samples with 100% of the tumor with no PTEN staining were classified as "ICR PTEN loss".
Measured: 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)
Phase II: Percentage of Participants With PSA Response (ITT Population)
PSA response was defined as a > 50% decrease in PSA from baseline, which was to be confirmed after ≥ 4 weeks by a confirmatory PSA measurement.
Measured: 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)
Phase II: Percentage of Participants With PSA Response in Participants With ICR PTEN Loss
PSA response was defined as a > 50% decrease in PSA from baseline, which was to be confirmed after ≥ 4 weeks by a confirmatory PSA measurement. PTEN status was assessed by RUO IHC assay that was performed at ICR, UK. Samples with 100% of the tumor with no PTEN staining were classified as "ICR PTEN loss".
Measured: 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)
Phase II: Percentage of Participants With Objective Response (ITT Population)
Objective response was defined as having a confirm response (CR) or partial response (PR) according to a RECIST 1.1. CR was defined as disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to <10 mm in short axis. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions.
Measured: 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)
Phase II: Percentage of Participants With Objective Response in Participants With ICR PTEN Loss
Objective response was defined as having a CR or PR according to a RECIST 1.1. CR was defined as disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to <10 mm in short axis. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. PTEN status was assessed by RUO IHC assay that was performed at ICR, UK. Samples with 100% of the tumor with no PTEN staining were classified as "ICR PTEN loss". Number of participants analyzed=participants with PTEN loss and evaluable for this endpoint.
Measured: 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)
Phase II: Duration of Tumor Response (ITT Population)
Duration of tumor response: time period from 1st documentation of objective response (CR/PR) (whichever status was recorded first) to date of 1st occurrence of investigator documented disease progression or death. CR: disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to <10 mm in short axis. PR: at least 30% decrease in sum of diameters of target lesions (taking as reference baseline sum diameters), no progression in non-target lesions, and no new lesions. Progression: increase by at least 20% in sum of longest diameters of each target lesion, taking as reference smallest sum of longest diameters or appearance of one or more new lesions. Duration of tumor response was estimated using Kaplan Meier method.
Measured: 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)
Phase II: Duration of Tumor Response in Participants With ICR PTEN Loss
Duration of tumor response: time period from 1st documentation of objective response (CR/PR) (whichever status was recorded first) to date of 1st occurrence of investigator documented disease progression or death. CR: disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to <10 mm in short axis. PR: at least 30% decrease in sum of diameters of target lesions (taking as reference baseline sum diameters), no progression in non-target lesions, and no new lesions. Progression: increase by at least 20% in sum of longest diameters of each target lesion, taking as reference smallest sum of longest diameters or appearance of one or more new lesions. Duration of tumor response was estimated using Kaplan Meier method.
Measured: 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)
Phase II: Percentage of Participants With Circulating Tumor Cells (CTC) Reduction Response (ITT Population)
CTC reduction response was defined as participants with a reduction in CTCs of ≥ 30% compared to baseline.
Measured: 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)
Phase II: Percentage of Participants With CTC Reduction Response in Participants With ICR PTEN Loss
CTC reduction response was defined as participants with a reduction in CTCs of ≥ 30% compared to baseline. PTEN status was assessed by RUO IHC assay that was performed at ICR, UK. Samples with 100% of the tumor with no PTEN staining were classified as "ICR PTEN loss".
Measured: 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)
Phase II: Percentage of Participants With CTC Conversion (ITT Population)
CTC conversion was defined as a decline to < 5 cells/7.5 milliliter (mL) post baseline among participants with CTC ≥ 5 cells/7.5 mL at baseline.
Measured: 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)
Phase II: Percentage of Participants With CTC Conversion in Participants With ICR PTEN Loss
CTC conversion was defined as a decline to < 5 cells/7.5 milliliter (mL) post baseline among participants with CTC ≥ 5 cells/7.5 mL at baseline. PTEN status was assessed by RUO IHC assay that was performed at ICR, UK. Samples with 100% of the tumor with no PTEN staining were classified as "ICR PTEN loss".
Measured: 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)
Phase II: Percentage of Participants With Pain Progression (ITT Population)
Pain progression was defined as ≥ 2 point-increase from baseline on the modified Brief Pain Inventory - short form (mBPI-sf). The mBPI-sf consists of four questions that assess pain intensity (worst, least, average, right now) and seven items within one question that assess the impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each item was assessed on 0-10 scale with 0 being no pain to 10 being worst imaginable pain. Total score was the average of individual item (range 0-10).
Measured: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years)
Phase II: Percentage of Participants With Pain Progression in Participants With ICR PTEN Loss
Pain progression was defined as ≥ 2 point-increase from baseline on the modified Brief Pain Inventory - short form (mBPI-sf). The mBPI-sf consists of four questions that assess pain intensity (worst, least, average, right now) and seven items within one question that assess the impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each item was assessed on 0-10 scale with 0 being no pain to 10 being worst imaginable pain. Total score was the average of individual item (range 0-10). PTEN status was assessed by RUO IHC assay that was performed at ICR, UK. Samples with 100% of the tumor with no PTEN staining were classified as "ICR PTEN loss".
Measured: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years)
Phase II: Time to Pain Progression (ITT Population)
Time to pain progression was defined as the time from screening till first occurrence of pain progression. Pain progression was defined as ≥ 2 point-increase from baseline on the modified Brief Pain Inventory - short form (mBPI-sf). The mBPI-sf consists of four questions that assess pain intensity (worst, least, average, right now) and seven items within one question that assess the impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each item was assessed on 0-10 scale with 0 being no pain to 10 being worst imaginable pain. Total score was the average of individual item (range 0-10).
Measured: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years)
Phase II: Time to Pain Progression in Participants With ICR PTEN Loss
Time to pain progression was defined as the time from screening till first occurrence of pain progression. Pain progression: ≥ 2 point-increase from baseline on the modified Brief Pain Inventory - short form (mBPI-sf). The mBPI-sf consists of 4questions that assess pain intensity (worst, least, average, right now) and seven items within one question that assess the impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each item was assessed on 0-10 scale with 0 being no pain to 10 being worst imaginable pain. Total score was the average of individual item (range 0-10). PTEN status was assessed by RUO IHC assay that was performed at ICR, UK. Samples with 100% of the tumor with no PTEN staining were classified as "ICR PTEN loss".
Measured: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years)
Phase II: Percentage of Participants With Adverse Events (AEs)
An Adverse Event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Measured: 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)
Phase II: Ipatasertib Plasma Concentrations When Co-Administered With Abiraterone
Measured: 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)
Phase II: G-037720 (Metabolite of Ipatasertib) Plasma Concentrations
G-037220 is N-dealkylated metabolite of ipatasertib and the main metabolite in circulation.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2011 (estimated)
- Study start11 Jan 2012
- Primary completion1 Sep 2015
- Study completion31 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 298 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01485861
- Sponsor's protocol ID
- GO27983
- Other IDs
- 2011-004126-10
- Status last verified
- Aug 2023
- First submitted
- 2 Dec 2011
- Last updated
- 14 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01485861
- Acronym / sponsor ID
- GO27983
- Conditions
- Prostate Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 298 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- 11 Jan 2012 (actual)
- Primary completion
- 1 Sep 2015 (actual)
- Study completion
- 31 Aug 2022 (actual)
- First posted
- 6 Dec 2011 (estimated)
- Results
- Posted 14 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Phase Ib: Ipatasertib 400 mg + abiraterone | Experimental | Drug: Abiraterone, Drug: Ipatasertib, Drug: Prednisone, Drug: PrednisoloneParticipants will receive ipatasertib 400 mg once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg twice daily (bid) continuously in 28-day treatment cycles until disease progression or intolerable toxicity. |
| Phase Ib: Apitolisib 30 mg + abiraterone | Experimental | Drug: Abiraterone, Drug: Apitolisib, Drug: Prednisone, Drug: PrednisoloneParticipants will receive apitolisib 30 mg once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg twice daily (bid) continuously in 28-day treatment cycles until disease progression or intolerable toxicity. |
| Phase II: Ipatasertib 400 mg + abiraterone | Experimental | Drug: Abiraterone, Drug: Ipatasertib, Drug: Prednisone, Drug: PrednisoloneParticipants will receive Ipatasertib 400 mg once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg bid continuously in 28-day treatment cycles until disease progression or intolerable toxicity. |
| Phase II: Ipatasertib 200 mg + abiraterone | Experimental | Drug: Abiraterone, Drug: Ipatasertib, Drug: Prednisone, Drug: PrednisoloneParticipants will receive Ipatasertib 200 mg once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg bid continuously in 28-day treatment cycles until disease progression or intolerable toxicity. |
| Phase II: Placebo + abiraterone | Placebo comparator | Drug: Abiraterone, Drug: Placebo, Drug: Prednisone, Drug: PrednisoloneParticipants will receive placebo (for Ipatasertib) once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg bid continuously in 28-day treatment cycles until disease progression or intolerable toxicity. |
| Safety Cohort: Ipataseritib 400 mg + Abiraterone + Prednisone | Experimental | Drug: Abiraterone, Drug: Ipatasertib, Drug: Prednisone, Drug: PrednisoloneParticipants will receive ipatasertib 400 mg orally once daily and/or prednisone/prednisolone 5 mg orally once daily or bid and/or abiraterone 1000 mg orally once daily according to the following schedule: ipatasertib in the morning during Cycle 1, Days 1-7; ipatasertib in the morning plus prednisone/prednisolone once at night during Cycle 1, Day 8; ipatasertib in the morning plus prednisone/prednisolone bid (morning and night) during Cycle 1, Days 9-11; ipatasertib in the morning plus prednisone/prednisolone bid (morning and night) and abiraterone in the morning during Cycle 1, Days 12-18; ipatasertib in the evening plus prednisone/prednisolone bid (morning and night) and abiraterone at the same time as ipatasertib during Cycle 1, Days 19-25; Cycle 2 and beyond ipatasertib once daily in the morning or evening, abiraterone at the same time as ipatasertib, and prednisone/prednisolone bid. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AbirateroneOrally once daily | Drug | Phase II: Ipatasertib 200 mg + abiraterone, Phase II: Ipatasertib 400 mg + abiraterone, Phase II: Placebo + abiraterone, Phase Ib: Apitolisib 30 mg + abiraterone, Phase Ib: Ipatasertib 400 mg + abiraterone, Safety Cohort: Ipataseritib 400 mg + Abiraterone + Prednisone |
| ApitolisibOrally once daily | Drug | Phase Ib: Apitolisib 30 mg + abiraterone |
| IpatasertibOrally once daily | Drug | Phase II: Ipatasertib 200 mg + abiraterone, Phase II: Ipatasertib 400 mg + abiraterone, Phase Ib: Ipatasertib 400 mg + abiraterone, Safety Cohort: Ipataseritib 400 mg + Abiraterone + Prednisone |
| PlaceboOrally once daily | Drug | Phase II: Placebo + abiraterone |
| PrednisoneOrally bid | Drug | Phase II: Ipatasertib 200 mg + abiraterone, Phase II: Ipatasertib 400 mg + abiraterone, Phase II: Placebo + abiraterone, Phase Ib: Apitolisib 30 mg + abiraterone, Phase Ib: Ipatasertib 400 mg + abiraterone, Safety Cohort: Ipataseritib 400 mg + Abiraterone + Prednisone |
| PrednisoloneOrally bid | Drug | Phase II: Ipatasertib 200 mg + abiraterone, Phase II: Ipatasertib 400 mg + abiraterone, Phase II: Placebo + abiraterone, Phase Ib: Apitolisib 30 mg + abiraterone, Phase Ib: Ipatasertib 400 mg + abiraterone, Safety Cohort: Ipataseritib 400 mg + Abiraterone + Prednisone |
Primary outcome
Phase Ib: Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: Days 1 to 28 of Cycle 1 (Cycle length = 28 days)
DLT: 1 of the following toxicities, at least possibly related to ipatasertib or apitolisib. 1) Grade ≥ 3 non-hematologic, non-hepatic major organ AE; 2) Grade ≥ 3 febrile neutropenia; 3) Grade ≥ 4 neutropenia (absolute neutrophils less than [<] 500 per microliter) lasting greater than (>) 7 days; 4) Grade ≥3 thrombocytopenia associated with acute hemorrhage; 5) Grade ≥4 thrombocytopenia; 6) Grade ≥4 anemia; 7) 1 episode of fasting Grade ≥4 hyperglycemia or 3 episodes of fasting Grade 3 hyperglycemia on separate days within 7 days, as determined by laboratory blood glucose evaluation; 8) Grade ≥3 elevation lasting for > 48 hours for hepatic transaminase or liver-specific alkaline phosphatase or total bilirubin. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v 4.0.
Phase Ib: Percentage of Participants With Adverse Events (AEs)
Time frame: 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).
An Adverse Event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Phase Ib: Recommended Phase II Dose (RP2D) of Ipatasertib and Apitolisib
Time frame: Days 1 to 28 of Cycle 1 (Cycle length = 28 days)
RP2D is a dose of a drug which would be used in Phase II stage of the study. RP2D was to be determined based on maximum tolerated dose (MTD) in Phase Ib stage of the study. The highest dose level (in 3+3 escalation scheme) with an acceptable safety profile and with a minimum of 6 participants at which fewer than one-third of participants experienced a DLT was declared the MTD and RP2D.
Phase II: Radiographic Progression Free Survival (rPFS) (Intent-To-Treat [ITT] Population)
Time frame: 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)
rPFS: Time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments via CT scan and bone scans, or death on study from any cause, whichever occurred first. Progression was defined as follows: Soft tissue mass (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1): at least 20% increase in sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Bone: ≥ 2 new bone lesions plus 2 additional at confirmation on a second bone scan ≥ 4 weeks later (< 12 weeks after randomization). ≥ 2 new bone lesions consistent with progression, without need for confirmatory bone scan (≥ 12 weeks after randomization).
Phase II: rPFS in Participants With Institute of Cancer Research (ICR) Phosphatase and Tensin Homolog (PTEN) Loss
Time frame: 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)
rPFS: Time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments via CT scan and bone scans, or death on study from any cause, whichever occurred first. Progression was defined as follows: Soft tissue mass (RECIST 1.1): at least 20% increase in sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Bone: ≥ 2 new bone lesions plus 2 additional at confirmation on 2nd bone scan ≥ 4 weeks later (< 12 weeks after randomization). ≥ 2 new bone lesions consistent with progression, without need for confirmatory bone scan (≥ 12 weeks after randomization). PTEN status was assessed by RUO IHC assay that was performed at ICR, UK. Samples with 100% of the tumor with no PTEN staining were classified as "ICR PTEN loss". Number of participants analyzed=participants with PTEN loss.
40 secondary outcomes
Phase Ib: Maximum Plasma Concentration (Cmax) of Ipatasertib When Co-Administered With Abiraterone
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Time to Cmax (Tmax) of Ipatasertib When Co-Administered With Abiraterone
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Area Under The Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) of Ipatasertib When Co-Administered With Abiraterone
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Total Body Clearance (CL/F) of Ipatasertib When Co-Administered With Abiraterone
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Accumulation Ratio of Ipatasertib When Co-Administered With Abiraterone
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Cmax of G-037720 (Metabolite of Ipatasertib)
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Tmax of G-037720 (Metabolite of Ipatasertib)
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: AUC0-24 of G-037720 (Metabolite of Ipatasertib)
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Accumulation Ratio of G-037720 (Metabolite of Ipatasertib)
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Cmax of Apitolisib When Co-Administered With Abiraterone
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Tmax of Apitolisib When Co-Administered With Abiraterone
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: AUC0-24 of Apitolisib When Co-Administered With Abiraterone
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Cmax of Abiraterone When Co-Administered With Ipatasertib or Apitolisib
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Tmax of Abiraterone When Co-Administered With Ipatasertib or Apitolisib
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: AUC0-24 of Abiraterone When Co-Administered With Ipatasertib or Apitolisib
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Plasma Half-Life of Abiraterone When Co-Administered With Ipatasertib or Apitolisib
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase Ib: Accumulation Ratio of Abiraterone When Co-Administered With Ipatasertib or Apitolisib
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)
Phase II: Overall Survival (ITT Population)
Time frame: 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)
Phase II: Overall Survival in Participants With ICR IHC PTEN Loss
Time frame: 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)
Phase II: Percentage of Participants With PSA Progression (ITT Population)
Time frame: 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)
Phase II: Percentage of Participants With PSA Progression in Participants With ICR PTEN Loss
Time frame: 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)
Phase II: Time to PSA Progression (ITT Population)
Time frame: 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)
Phase II: Time to PSA Progression in Participants With ICR PTEN Loss
Time frame: 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)
Phase II: Percentage of Participants With PSA Response (ITT Population)
Time frame: 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)
Phase II: Percentage of Participants With PSA Response in Participants With ICR PTEN Loss
Time frame: 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)
Phase II: Percentage of Participants With Objective Response (ITT Population)
Time frame: 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)
Phase II: Percentage of Participants With Objective Response in Participants With ICR PTEN Loss
Time frame: 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)
Phase II: Duration of Tumor Response (ITT Population)
Time frame: 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)
Phase II: Duration of Tumor Response in Participants With ICR PTEN Loss
Time frame: 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)
Phase II: Percentage of Participants With Circulating Tumor Cells (CTC) Reduction Response (ITT Population)
Time frame: 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)
Phase II: Percentage of Participants With CTC Reduction Response in Participants With ICR PTEN Loss
Time frame: 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)
Phase II: Percentage of Participants With CTC Conversion (ITT Population)
Time frame: 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)
Phase II: Percentage of Participants With CTC Conversion in Participants With ICR PTEN Loss
Time frame: 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)
Phase II: Percentage of Participants With Pain Progression (ITT Population)
Time frame: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years)
Phase II: Percentage of Participants With Pain Progression in Participants With ICR PTEN Loss
Time frame: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years)
Phase II: Time to Pain Progression (ITT Population)
Time frame: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years)
Phase II: Time to Pain Progression in Participants With ICR PTEN Loss
Time frame: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years)
Phase II: Percentage of Participants With Adverse Events (AEs)
Time frame: 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)
Phase II: Ipatasertib Plasma Concentrations When Co-Administered With Abiraterone
Time frame: 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)
Phase II: G-037720 (Metabolite of Ipatasertib) Plasma Concentrations
Time frame: 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Prostate Cancer, Leukemia
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STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Recruiting
Rehabilitation and Sex Therapy to Optimize Recovery After Prostate Cancer Treatment
Prostate Cancer, Urinary Incontinence
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Genentech, Inc.
59 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Abiraterone, Apitolisib and Ipatasertib in people with Prostate Cancer, run by Genentech, Inc. at 59 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 59 sites in United States, Spain, France, United Kingdom, Czechia and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase Ib: Percentage of Participants With Dose-Limiting Toxicities (DLTs) (time frame: Days 1 to 28 of Cycle 1 (Cycle length = 28 days)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2023.