Study of Ipatasertib or Apitolisib With Abiraterone Acetate Versus Abiraterone Acetate in Participants With Castration-Resistant Prostate Cancer Previously Treated With Docetaxel Chemotherapy

Sponsor
Genentech, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT01485861
Collaborator
(none)
273
Enrollment
61
Locations
6
Arms
125.6
Anticipated Duration (Months)
4.5
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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in combination with abiraterone and of apitolisib administrated in combination with abiraterone (this phase is no longer active), a Phase II, 3-arm, double-blind, randomized comparison of ipatasertib with abiraterone and prednisone/prednisolone versus placebo with abiraterone and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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
273 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Masking Description:
In Phase II participants and investigators were blinded with regard to treatment status (i.e., ipatasertib vs. placebo). Phase Ib and the safety cohort were open-label.
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jan 11, 2012
Actual Primary Completion Date :
Sep 1, 2015
Anticipated Study Completion Date :
Jul 1, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: Phase Ib: Ipatasertib 400 mg + abiraterone

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.

Drug: Abiraterone
Orally once daily

Drug: Ipatasertib
Orally once daily

Drug: Prednisone
Orally bid

Drug: Prednisolone
Orally bid

Experimental: Phase Ib: Apitolisib 30 mg + abiraterone

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.

Drug: Abiraterone
Orally once daily

Drug: Apitolisib
Orally once daily

Drug: Prednisone
Orally bid

Drug: Prednisolone
Orally bid

Experimental: Phase II: Ipatasertib 400 mg + abiraterone

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.

Drug: Abiraterone
Orally once daily

Drug: Ipatasertib
Orally once daily

Drug: Prednisone
Orally bid

Drug: Prednisolone
Orally bid

Experimental: Phase II: Ipatasertib 200 mg + abiraterone

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.

Drug: Abiraterone
Orally once daily

Drug: Ipatasertib
Orally once daily

Drug: Prednisone
Orally bid

Drug: Prednisolone
Orally bid

Placebo Comparator: Phase II: Placebo + abiraterone

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.

Drug: Abiraterone
Orally once daily

Drug: Placebo
Orally once daily

Drug: Prednisone
Orally bid

Drug: Prednisolone
Orally bid

Experimental: Safety Cohort: Ipataseritib 400 mg + Abiraterone + Prednisone

Participants will receive Ipataseritib 400 mg once daily in the AM for Cycle 1 day 1-18. On Day 19, Ipataseritib 400 mg will be switched to PM dosing for the remainder of the Cycle 1. Prednisone 5 mg starts in the PM of Cycle 1 day 8 and taken BID thereafter for the remainder of the study treatment Abiraterone 1000mg once a day starts on Cycle1 day 12 in the AM and should be taken at the same time as Ipataseritib. Starting from cycle 1 day 19, Ipataseritib and Abiraterone are dosed in PM at should be taken together at the same time each day until cycle 2 day 1. Starting from Cycle 2 Day 1, Participants may choose to take Ipatasertib and Abiraterone in either the AM or PM; however, they should be taken together at approximately the same time each day. Participants will receive the study treatment until disease progression or intolerable toxicity.

Drug: Abiraterone
Orally once daily

Drug: Ipatasertib
Orally once daily

Drug: Prednisone
Orally bid

Drug: Prednisolone
Orally bid

Outcome Measures

Primary Outcome Measures

  1. Phase Ib: Percentage of Participants With Dose Limiting Toxicity (DLTs) [Days 1 to 28 of Cycle 1 (Cycle length = 28 days)]

  2. Phase Ib: Percentage of Participants with Adverse Events (AEs) [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 3.6 years overall)]

  3. Phase Ib: Recommended Phase II Dose (RP2D) of Ipatasertib [Days 1 to 28 of Cycle 1 (Cycle length = 28 days)]

  4. Phase II: Radiographic Progression Free Survival (rPFS) - ITT Population [Screening up to radiographic progression or death, whichever occurs first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter, and at treatment completion [up to 3.6 years overall]) (cycle length = 28 days)]

  5. Phase II: rPFS in Participants With Institute of Cancer Research (ICR) Phosphatase and Tensin Homolog (PTEN) Loss [Screening up to radiographic progression or death, whichever occurs first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter, and at treatment completion [up to 3.6 years overall]) (cycle length = 28 days)]

Secondary Outcome Measures

  1. Phase Ib: Maximum Plasma Concentration (Cmax) of Ipatasertib When Co-Administered With Abiraterone [Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)]

  2. Phase Ib: Time to Cmax (tmax) of Ipatasertib When Co-Administered With Abiraterone [Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)]

  3. Phase Ib: Area Under The Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) of Ipatasertib When Co-Administered With Abiraterone [Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)]

  4. Phase Ib: Total Body Clearance (CL/F) of Ipatasertib When Co-Administered With Abiraterone [Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)]

  5. Phase Ib: Accumulation Ratio of Ipatasertib When Co-Administered With Abiraterone [Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)]

  6. Phase Ib: Cmax of G-037720 (Metabolite of Ipatasertib) [Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)]

  7. Phase Ib: tmax of G-037720 (Metabolite of Ipatasertib) [Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)]

  8. Phase Ib: AUC0-24 of G-037720 (Metabolite of Ipatasertib) [Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Day 15 of Cycle 1 (cycle length=28 days)]

  9. Phase Ib: Accumulation Ratio of G-037720 (Metabolite of Ipatasertib) [Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)]

  10. Phase Ib: Cmax of Apitolisib When Co-Administered With Abiraterone [Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)]

  11. Phase Ib: tmax of Apitolisib When Co-Administered With Abiraterone [Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)]

  12. Phase Ib: AUC0-24 of Apitolisib When Co-Administered With Abiraterone [Pre-dose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length = 28 days)]

  13. Phase Ib: Cmax of Abiraterone When Co-Administered With Ipatasertib or Apitolisib [Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)]

  14. Phase Ib: tmax of Abiraterone When Co-Administered With Ipatasertib or Apitolisib [Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)]

  15. Phase Ib: AUC0-24 of Abiraterone When Co-Administered With Ipatasertib or Apitolisib [Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)]

  16. Phase Ib: Plasma Half-Life of Abiraterone When Co-Administered With Ipatasertib or Apitolisib [Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)]

  17. Phase Ib: Accumulation Ratio of Abiraterone When Co-Administered With Ipatasertib or Apitolisib [Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)]

  18. Phase II: Overall Survival - ITT Population [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)]

  19. Phase II: Overall Survival in Participants With ICR PTEN Loss [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)]

  20. Phase II: Prostate Specific Antigen (PSA) Response Rate (ITT Population) [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)]

  21. Phase II: PSA Response Rate in Participants With ICR PTEN Loss [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)]

  22. Phase II: Objective Response Rate as Assessed by RECIST 1.1 (ITT Population) [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)]

  23. Phase II: Objective Response Rate as Assessed by RECIST 1.1 in Participants With ICR PTEN Loss [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)]

  24. Phase II: Duration of Tumor Response (ITT Population) [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)]

  25. Phase II: Duration of Tumor Response in Participants with ICR PTEN Loss [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)]

  26. Phase II: Percentage of Participants With Circulating Tumor Cells (CTC) Reduction Response (ITT Population) [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)]

  27. Phase II: Percentage of Participants With CTC Reduction Response in Participants With ICR PTEN Loss [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)]

  28. Phase II: Percentage of Participants With Pain Progression (ITT Population) [Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years)]

  29. Phase II: Percentage of Participants With Pain Progression in Participants With ICR PTEN Loss [Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years)]

  30. Phase II: Time to Pain Progression (ITT Population) [Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years)]

  31. Phase II: Time to Pain Progression in Participants With ICR PTEN Loss [Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years)]

  32. Phase II: Percentage of Participants With Adverse Events (AEs) [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 8.9 years)]

  33. Phase II: Ipatasertib Plasma Concentrations When Co-Administered With Abiraterone [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)]

  34. Phase II: G-037720 (Metabolite of Ipatasertib) Plasma Concentrations [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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1HonorHealth Research Institute - BisgroveScottsdaleArizonaUnited States85258
2Pacific Hematology Oncology AssociatesSan FranciscoCaliforniaUnited States94115
3Florida Cancer Specialists - Fort Myers (New Hampshire Ct)Fort MyersFloridaUnited States33901-8101
4Florida Cancer Specialists; SarasotaSarasotaFloridaUnited States34232
5Kaiser Permanente Medical CtrHonoluluHawaiiUnited States96819
6Johns Hopkins Univ; Bunting Blaustein Cancer CenterBaltimoreMarylandUnited States21231
7Karmanos Cancer InstituteDetroitMichiganUnited States48201
8Urology Cancer Center & GU Research NetworkOmahaNebraskaUnited States68130
9New York Cancer and Blood Specialists - Setauket Medical OncologyEast SetauketNew YorkUnited States11733
10Weill Cornell Medical CollegeNew YorkNew YorkUnited States10065
11Carolina Urologic Research CenterMyrtle BeachSouth CarolinaUnited States29572
12Sarah Cannon Cancer Center - Tennessee Oncology, PllcNashvilleTennesseeUnited States37203
13Masarykuv onkologicky ustavBrnoCzechia656 53
14Fakultni nemocnice Hradec Kralove; I. interni klinika,Oddeleni invazivni kardiologieHradec KraloveCzechia50012
15Urocentrum Praha s.r.o.Praha 2Czechia120 00
16Vseobecna fakultni nemocnice v PrazePraha 2Czechia128 08
17Fakultni Thomayerova Nemocnice; Revmatologicke OddeleniPrahaCzechia140 59
18ICO Paul Papin; Oncologie Medicale.AngersFrance49055
19Centre Léon Bérard - Centre régional de lutte contre le cancer Rhône-AlpesLyonFrance69008
20Hia Du Val De GraceParisFrance75230
21Institut Curie; Oncologie MedicaleParisFrance75231
22GH Paris Saint Joseph; Hopital De Jour OncologieParisFrance75674
23Hopital d'Instruction des Armees de BeginSaint-MandeFrance94160
24Institut Gustave Roussy; Departement Oncologie MedicaleVillejuifFrance94805
25Alexandras Hospital; Dept. of Clin. Therapeutics, Athens Uni School of MedicineAthensGreece115 28
26Univ General Hosp Heraklion; Medical OncologyHeraklionGreece711 10
27University Hospital of Patras Medical OncologyPatrasGreece265 04
28Metropolitan Hospital; 2Nd Oncology ClinicPiraeusGreece185 47
29University Hospital of Larissa; OncologyΛαρισαGreece413 35
30IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia MedicaMeldolaEmilia-RomagnaItaly47014
31Azienda Ospedaliera San Camillo Forlanini; Oncologia MedicaRomaLazioItaly00152
32Azienda Ospedaliera Istituti OspitalieriCremonaLombardiaItaly26100
33Irccs Ospedale San Raffaele;Oncologia MedicaMilanoLombardiaItaly20132
34Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2MilanoLombardiaItaly20133
35Ospedale S. Donato; Divisione Di ReumatologiaArezzoToscanaItaly52100
36Het Nederlands Kanker InstAmsterdamNetherlands1066 EC
37Vu Medisch Centrum; Afdeling LongziektenAmsterdamNetherlands1081 HV
38MC Haaglanden; OncologieDen HaagNetherlands2512 VA
39UMC St RadboudNijmegenNetherlands6525 GA
40Sint Franciscus Gasthuis; Inwendige GeneeskundeRotterdamNetherlands3045 PM
41Sf. Constantin Hospital; OncologyBrasovRomania500019
42Prof. Dr. Th. Burghele Clin Urology HospBucharestRomania050659
43Prof. Dr. I. Chiricuta Institute of OncologyCluj NapocaRomania400015
44Institute of Oncology "Prof. Dr. I. Chiricuta"Cluj-NapocaRomania400015
45ONCOMED - Medical CentreTimisoaraRomania300239
46Municipal Hosp Turdal; OncologyTurdaRomania401103
47Hospital General Universitario de Elche; Servicio de OncologiaElcheAlicanteSpain03203
48Hospital Universitari Germans Trias i Pujol; Servicio de OncologiaBadalonaBarcelonaSpain08916
49Corporacio Sanitaria Parc Tauli; Servicio de OncologiaSabadellBarcelonaSpain8208
50Clinica Universitaria de NavarraPamplonaNavarraSpain31008
51Hospital Univ Vall d'Hebron; Servicio de OncologiaBarcelonaSpain08035
52Hospital General Universitario Gregorio MarañonMadridSpain28007
53Hospital Universitario 12 de Octubre; Servicio de OncologiaMadridSpain28041
54Hospital Madrid Norte SanchinarroMadridSpain28050
55Hospital Clinico Universitario Virgen de la VictoriaMalagaSpain29010
56Queen Elizabeth Hospital; Centre for Clinical HaematologyBirminghamUnited KingdomB15 2TH
57Gartnavel General HospitalGlasgowUnited KingdomG12 0XH
58St. James University Hospital; Pharmacy DepartmentLeedsUnited KingdomLS9 7TF
59The Clatterbridge Cancer Centre NHS Foundation TrustLiverpoolUnited KingdomL7 8YA
60Sarah Cannon Research InstituteLondonUnited KingdomW1G 6AD
61The Royal Marsden HospitalSuttonUnited KingdomSM2 5PT

Sponsors and Collaborators

  • Genentech, Inc.

Investigators

  • Study Director: Clinical Trials, Genentech, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01485861
Other Study ID Numbers:
  • GO27983
  • 2011-004126-10
First Posted:
Dec 6, 2011
Last Update Posted:
Oct 4, 2021
Last Verified:
Sep 1, 2021
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 4, 2021