Clinical Trials /

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

NCT01485861

Description:

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in combination with abiraterone and of GDC-0980 administrated in combination with abiraterone (this phase is no longer active), a Phase II, 3-arm, double-blind, randomized comparison of ipatasertib with abiraterone and prednisone/prednisolone versus placebo with abiraterone and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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Ipatasertib or GDC-0980 With Abiraterone Acetate Versus Coralie in Participants With Castration-Resistant Prostate Cancer Previously Treated With Docetaxel Chemotherapy
  • Official Title: A Phase Ib/II Study of GDC-0068 or GDC-0980 With Abiraterone Acetate Versus Abiraterone Acetate in Patients With Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: GO27983
  • SECONDARY ID: 2011-004126-10
  • NCT ID: NCT01485861

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
AbirateronePhase Ib: Ipatasertib 400 mg + abiraterone
GDC-0980Phase Ib: GDC-0980 30 mg + abiraterone
IpatasertibPhase Ib: Ipatasertib 400 mg + abiraterone
PlaceboPhase II: Placebo + abiraterone
PrednisonePhase Ib: Ipatasertib 400 mg + abiraterone
PrednisolonePhase Ib: Ipatasertib 400 mg + abiraterone

Purpose

This multicenter, international, Phase Ib/II trial consists of two stages: a Phase Ib, open-label stage in which the recommended Phase II dose will be determined for ipatasertib and GDC-0980 in combination with abiraterone and prednisone/prednisolone and a Phase II, 3-arm, double-blind, randomized comparison of ipatasertib with abiraterone and prednisone/prednisolone versus placebo with abiraterone and prednisone/prednisolone.

Trial Arms

NameTypeDescriptionInterventions
Phase Ib: Ipatasertib 400 mg + abirateroneExperimentalParticipants 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.
  • Abiraterone
  • Ipatasertib
  • Prednisone
  • Prednisolone
Phase Ib: GDC-0980 30 mg + abirateroneExperimentalParticipants will receive GDC-0980 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.
  • Abiraterone
  • GDC-0980
  • Prednisone
  • Prednisolone
Phase II: Ipatasertib 400 mg + abirateroneExperimentalParticipants 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.
  • Abiraterone
  • Ipatasertib
  • Prednisone
  • Prednisolone
Phase II: Ipatasertib 200 mg + abirateroneExperimentalParticipants 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.
  • Abiraterone
  • Ipatasertib
  • Prednisone
  • Prednisolone
Phase II: Placebo + abirateronePlacebo ComparatorParticipants 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.
  • Abiraterone
  • Placebo
  • Prednisone
  • Prednisolone

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed metastatic or advanced prostate adenocarcinoma that has been
             previously treated with docetaxel and has progressed during treatment of at least one
             hormonal therapy

          -  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

        Exclusion Criteria:

          -  History of Type I or Type II diabetes mellitus requiring insulin

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase Ib: Percentage of Participants With Dose Limiting Toxicity (DLTs)
Time Frame:Days 1 to 28 of Cycle 1 (Cycle length = 28 days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Phase II: Percentage of Participants Who Died - 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 3.6 years overall]) (cycle length = 28 days)
Safety Issue:
Description:
Measure: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 3.6 years overall]) (cycle length = 28 days)
Safety Issue:
Description:
Measure:Phase II: Percentage of Participants Who Died in Participants With ICR 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 3.6 years overall]) (cycle length = 28 days)
Safety Issue:
Description:
Measure:Phase II: Overall Survival in Participants With ICR 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 3.6 years overall]) (cycle length = 28 days)
Safety Issue:
Description:
Measure:Phase II: Percentage of Participants With Prostate-Specific Antigen (PSA) Progression (as Assessed by Prostate Cancer Working Group 2 Criteria) - 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)
Safety Issue:
Description:
Measure:Phase II: Time to PSA Progression (as Assessed by Prostate Cancer Working Group 2 Criteria) - 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)
Safety Issue:
Description:
Measure:Phase II: Percentage of Participants With PSA Progression (as Assessed by Prostate Cancer Working Group 2 Criteria) 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)
Safety Issue:
Description:
Measure:Phase II: Time to PSA Progression (as Assessed by Prostate Cancer Working Group 2 Criteria) 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)
Safety Issue:
Description:
Measure:Phase II: Percentage of Participants With PSA Response - ITT Population
Time Frame: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)
Safety Issue:
Description:
Measure:Phase II: Percentage of Participants With PSA Response in Participants With ICR PTEN Loss
Time Frame: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)
Safety Issue:
Description:
Measure:Phase II: Percentage of Participants With Objective Response as Assessed by RECIST 1.1 - 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)
Safety Issue:
Description:
Measure:Phase II: Percentage of Participants With Objective Response (as Assessed by RECIST 1.1) 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)
Safety Issue:
Description:
Measure:Phase II: Duration of Tumor Response, as Assessed by RECIST 1.1 - 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)
Safety Issue:
Description:
Measure:Phase II: Percentage of Participants With Circulating Tumor Cells (CTC) Reduction Response - ITT Population
Time Frame:Screening, 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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure:Phase Ib: Maximum Plasma Concentration (Cmax) (in nanograms per milliliter [ng/mL]) of Ipatasertib and GDC-0980 When Co-Administered With Abiraterone
Time Frame:Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)
Safety Issue:
Description:
Measure:Phase Ib: Time to Cmax (tmax) (in hours) of Ipatasertib and GDC-0980 When Co-Administered With Abiraterone
Time Frame:Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)
Safety Issue:
Description:
Measure:Phase Ib: Area Under The Concentration Time Curve From Time 0 to 24 Hours (AUC0-24) (in ng/mL*hours) of Ipatasertib and GDC-0980 When Co-Administered With Abiraterone
Time Frame:Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)
Safety Issue:
Description:
Measure:Phase Ib: Total Body Clearance (CL/F) of Ipatasertib When Co-Administered With Abiraterone
Time Frame:Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Day 15 of Cycle 1 (cycle length=28 days)
Safety Issue:
Description:
Measure:Phase Ib: Accumulation Ratio of Ipatasertib When Co-Administered With Abiraterone
Time Frame:Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)
Safety Issue:
Description:
Measure:Cmax of G-037720 (Metabolite of Ipatasertib)
Time Frame:Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)
Safety Issue:
Description:
Measure:tmax of G-037720 (Metabolite of Ipatasertib)
Time Frame:Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)
Safety Issue:
Description:
Measure:Phase Ib: AUC0-24 of G-037720 (Metabolite of Ipatasertib)
Time Frame:Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)
Safety Issue:
Description:
Measure:Phase Ib: Accumulation Ratio of G-037720 (Metabolite of Ipatasertib)
Time Frame:Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)
Safety Issue:
Description:
Measure:Phase Ib: Cmax of Abiraterone When Co-Administered With Ipatasertib or GDC-0980
Time Frame:Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)
Safety Issue:
Description:
Measure:Phase Ib: tmax of Abiraterone When Co-Administered With Ipatasertib or GDC-0980
Time Frame:Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)
Safety Issue:
Description:
Measure:Phase Ib: AUC0-24 of Abiraterone When Co-Administered With Ipatasertib or GDC-0980
Time Frame:Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)
Safety Issue:
Description:
Measure:Phase Ib: Plasma Half-Life of Abiraterone When Co-Administered With Ipatasertib or GDC-0980
Time Frame:Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)
Safety Issue:
Description:
Measure:Phase Ib: Accumulation Ratio of Abiraterone When Co-Administered With Ipatasertib or GDC-0980
Time Frame:Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Genentech, Inc.

Last Updated

March 20, 2017