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with abiraterone (this phase is no longer active), a Phase II, 3-arm, double-blind,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.
Title
- Brief Title: Study of Ipatasertib or Apitolisib With Abiraterone Acetate Versus Abiraterone Acetate in Participants With Castration-Resistant Prostate Cancer Previously Treated With Docetaxel Chemotherapy
- Official Title: A Phase Ib/II Study of Ipatasertib (GDC-0068) or Apitolisib (GDC-0980) With Abiraterone Acetate Versus Abiraterone Acetate in Patients With Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Chemotherapy
Clinical Trial IDs
- ORG STUDY ID:
GO27983
- SECONDARY ID:
2011-004126-10
- NCT ID:
NCT01485861
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Abiraterone | | Phase II: Ipatasertib 200 mg + abiraterone |
| Apitolisib | | Phase Ib: Apitolisib 30 mg + abiraterone |
| Ipatasertib | | Phase II: Ipatasertib 200 mg + abiraterone |
| Placebo | | Phase II: Placebo + abiraterone |
| Prednisone | | Phase II: Ipatasertib 200 mg + abiraterone |
| Prednisolone | | Phase II: Ipatasertib 200 mg + abiraterone |
Purpose
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with abiraterone (this phase is no longer active), a Phase II, 3-arm, double-blind,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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 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. | - Abiraterone
- Ipatasertib
- Prednisone
- 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. | - Abiraterone
- Apitolisib
- Prednisone
- 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. | - Abiraterone
- Ipatasertib
- Prednisone
- 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. | - Abiraterone
- Ipatasertib
- Prednisone
- 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. | - Abiraterone
- Placebo
- Prednisone
- Prednisolone
|
| Safety Cohort: Ipataseritib 400 mg + Abiraterone + Prednisone | Experimental | 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. | - Abiraterone
- Ipatasertib
- Prednisone
- Prednisolone
|
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed metastatic or advanced prostate adenocarcinoma that has been
previously treated with docetaxel-based therapy and has progressed during treatment of
at least one hormonal therapy(prior docetaxel is not required for the safety cohort)
- Two rising PSA levels greater than or equal to (>/=) 2 ng/mL measured >/= 1 week apart
or radiographic evidence of disease progression in soft tissue or bone
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening
- Adequate hematologic and organ function
- Documented willingness to use an effective means of contraception
- Safety cohort only: agreement to use CGM for first cycle of treatment
Exclusion Criteria:
- History of Type I or Type II diabetes mellitus requiring insulin; safety cohort:
patients who are receiving any pharmacologic treatment for diabetes are not eligible
- New York Heart Association Class III or IV heart failure or Left ventricular ejection
fraction < 50% or ventricular arrhythmia requiring medication
- Significant atherosclerotic disease, as evidenced by: unstable angina, history of
myocardial infarction within 6 months prior to Day 1, or cerebrovascular accident
within 6 months prior to Day 1
- Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory
drugs or active inflammatory disease which requires immunosuppressive therapy
- Clinically significant history of liver disease
- History of adrenal insufficiency or hyperaldosteronism
- Phase II only: Previous therapy for prostate cancer with 17
alpha-hydroxylase/C17,20-lyase inhibitors, including abiraterone
- Phase II only: Previous treatment for prostate cancer with Protein kinase B
phosphatidylinositol 3 kinase and/or mammalian target of rapamycin inhibitors
- Need for chronic corticosteroid therapy of >/= 20 mg of prednisone per day or an
equivalent dose of other anti inflammatory corticosteroids or immunosuppressant
| 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 Apitolisib 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 Apitolisib 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 Apitolisib 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 Apitolisib |
| 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 Apitolisib |
| 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 Apitolisib |
| 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 Apitolisib |
| 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 Apitolisib |
| 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: | Safety Cohort: Percentage of Participants with AEs, Graded According to the NCI CTCAE v4.0 |
| Time Frame: | Day -1 of Cycle 1 to Day 1 of Cycle 2 (cycle length=25 days) |
| Safety Issue: | |
| Description: | |
| Measure: | Safety Cohort: Comparing of Average and Peak Glucose over 24h by CGM for Participants Receiving Ipataseritib+Prednisone+Abiraterone with AM Dosing of Ipatasertib |
| Time Frame: | Day -1 of Cycle 1 to Day 1 of Cycle 2 (cycle lenght=25 days) |
| Safety Issue: | |
| Description: | |
| Measure: | Safety Cohort: Comparing of Average and Peak Glucose over 24h by CGM for Participants Receiving Ipataseritib+Prednisone+Abiraterone with PM Dosing of Ipatasertib |
| Time Frame: | Day -1 of Cycle 1 to Day 1 of Cycle 2 (cycle lenght=25 days) |
| Safety Issue: | |
| Description: | |
| Measure: | Safety Cohort: Comparing of Average and Peak Glucose Over 24h by CGM for Participants Receiving Ipatasertib Alone |
| Time Frame: | Day -1 of Cycle 1 to Day 1 of Cycle 2 (cycle lenght=25 days) |
| Safety Issue: | |
| Description: | |
| Measure: | Safety Cohort: Comparing of Average and Peak Glucose Over 24h by CGM for Participants Receiving Ipatasertib+Prednisone |
| Time Frame: | Day -1 of Cycle 1 to Day 1 of Cycle 2 (cycle lenght=25 days) |
| Safety Issue: | |
| Description: | |
| Measure: | Safety Cohort: Comparing of Average and Peak Glucose Over 24h by CGM for Participants Receiving Ipatasertib+Prednisone+Abiraterone |
| Time Frame: | Day -1 of Cycle 1 to Day 1 of Cycle 2 (cycle lenght=25 days) |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Genentech, Inc. |
Last Updated
September 11, 2020
