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 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with abiraterone (this phase is no longer active), a Phase II, 3-arm, double-blind,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.
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 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with abiraterone (this phase is no longer active), a Phase II, 3-arm, double-blind,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.
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 Ib: Maximum Plasma Concentration (Cmax) 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) 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) 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 Days 1, 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: | Phase Ib: 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: | Phase Ib: 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 Day 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: | 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) |
| 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 8.9 years overall]) (cycle length = 28 days) |
| Safety Issue: | |
| Description: | |
| Measure: | Phase II: Prostate Specific Antigen (PSA) Response Rate (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) |
| Safety Issue: | |
| Description: | |
| Measure: | Phase II: PSA Response Rate 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Phase II: Objective Response Rate 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: Objective Response Rate 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 (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: 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) |
| Safety Issue: | |
| Description: | |
| Measure: | 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) |
| 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 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 (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 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: Plasma Concentration of Ipatasertib |
| Time Frame: | Cycle 1, Day 1: 1 and 4 hours post-dose; Cycle 1, Day 15: predose, 2 and 4 hours post-dose; Cycle 2, Day 1: predose and 1-4 hours post-dose (cycle length=28 days) |
| Safety Issue: | |
| Description: | |
| Measure: | 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 occurs first (up to 8.9 years) |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Genentech, Inc. |
Last Updated
August 27, 2021
