Phase 2
Completed N=20
Study of Ipatasertib or Apitolisib With Abiraterone Acetate Versus Abiraterone Acetate in Participants With Castration-Resistant Prostate Cancer Previously Treated With Docetaxel Chemotherapy
Source: ClinicalTrials.gov NCT01485861 ↗Enrolled (actual)
20
Serious AEs
41.3%
Results posted
Sep 2023
Primary outcomePrimary: Phase Ib: Percentage of Participants With Dose-Limiting Toxicities (DLTs) — 0; 0 percentage of participants
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in combination with abiraterone and of apitolisib administrated in combination with abiraterone (this phase is no longer active), a Phase II, 3-arm, double-blind, randomized comparison of ipatasertib with abiraterone and prednisone/prednisolone versus placebo with abiraterone and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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase Ib: Percentage of Participants With Dose-Limiting Toxicities (DLTs) |
0; 0 | — |
| PRIMARY Phase Ib: Percentage of Participants With Adverse Events (AEs) |
100.0; 100.0 | — |
| PRIMARY Phase Ib: Recommended Phase II Dose (RP2D) of Ipatasertib and Apitolisib |
400; NA | — |
| PRIMARY Phase II: Radiographic Progression Free Survival (rPFS) (Intent-To-Treat [ITT] Population) |
8.18; 8.31; 6.37 | 0.1606 |
| PRIMARY Phase II: rPFS in Participants With Institute of Cancer Research (ICR) Phosphatase and Tensin Homolog (PTEN) Loss |
11.53; 11.10; 4.60 | 0.0064 sig |
| SECONDARY Phase Ib: Maximum Plasma Concentration (Cmax) of Ipatasertib When Co-Administered With Abiraterone |
269; 466 | — |
| SECONDARY Phase Ib: Time to Cmax (Tmax) of Ipatasertib When Co-Administered With Abiraterone |
2.00; 2.02 | — |
| SECONDARY Phase Ib: Area Under The Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) of Ipatasertib When Co-Administered With Abiraterone |
1710; 3290 | — |
| SECONDARY Phase Ib: Total Body Clearance (CL/F) of Ipatasertib When Co-Administered With Abiraterone |
99600 | — |
| SECONDARY Phase Ib: Accumulation Ratio of Ipatasertib When Co-Administered With Abiraterone |
1.82 | — |
| SECONDARY Phase Ib: Cmax of G-037720 (Metabolite of Ipatasertib) |
117; 326 | — |
| SECONDARY Phase Ib: Tmax of G-037720 (Metabolite of Ipatasertib) |
2.00; 2.10 | — |
| SECONDARY Phase Ib: AUC0-24 of G-037720 (Metabolite of Ipatasertib) |
839; 2850 | — |
| SECONDARY Phase Ib: Accumulation Ratio of G-037720 (Metabolite of Ipatasertib) |
2.79 | — |
| SECONDARY Phase Ib: Cmax of Apitolisib When Co-Administered With Abiraterone |
190; 193 | — |
| SECONDARY Phase Ib: Tmax of Apitolisib When Co-Administered With Abiraterone |
2.02; 2.04 | — |
| SECONDARY Phase Ib: AUC0-24 of Apitolisib When Co-Administered With Abiraterone |
1600; 1640 | — |
| SECONDARY Phase Ib: Cmax of Abiraterone When Co-Administered With Ipatasertib or Apitolisib |
151; 88.2; 140; 52.7 | — |
| SECONDARY Phase Ib: Tmax of Abiraterone When Co-Administered With Ipatasertib or Apitolisib |
2.05; 2.01; 2.17; 3.04 | — |
| SECONDARY Phase Ib: AUC0-24 of Abiraterone When Co-Administered With Ipatasertib or Apitolisib |
749; 475; 961; 220 | — |
| SECONDARY Phase Ib: Plasma Half-Life of Abiraterone When Co-Administered With Ipatasertib or Apitolisib |
5.25; 7.68; 6.92; 14.70 | — |
| SECONDARY Phase Ib: Accumulation Ratio of Abiraterone When Co-Administered With Ipatasertib or Apitolisib |
0.823; 0.882 | — |
| SECONDARY Phase II: Overall Survival (ITT Population) |
18.27; 17.31; 18.37 | 0.4170 |
| SECONDARY Phase II: Overall Survival in Participants With ICR IHC PTEN Loss |
17.12; 28.45; 17.28 | 0.1472 |
| SECONDARY Phase II: Percentage of Participants With PSA Progression (ITT Population) |
57.1; 69.8; 72.3 | — |
| SECONDARY Phase II: Percentage of Participants With PSA Progression in Participants With ICR PTEN Loss |
72.0; 64.0; 66.7 | — |
| SECONDARY Phase II: Time to PSA Progression (ITT Population) |
5.55; 3.78; 3.71 | = 0.0665 |
| SECONDARY Phase II: Time to PSA Progression in Participants With ICR PTEN Loss |
3.71; 2.92; 2.79 | = 0.2906 |
| SECONDARY Phase II: Percentage of Participants With PSA Response (ITT Population) |
36.9; 33.7; 34.9 | = 0.7913 |
| SECONDARY Phase II: Percentage of Participants With PSA Response in Participants With ICR PTEN Loss |
40.0; 44.0; 28.6 | = 0.4176 |
| SECONDARY Phase II: Percentage of Participants With Objective Response (ITT Population) |
32.4; 23.1; 22.9 | = 0.3646 |
| SECONDARY Phase II: Percentage of Participants With Objective Response in Participants With ICR PTEN Loss |
11.1; 26.7; 14.3 | = 0.8489 |
| SECONDARY Phase II: Duration of Tumor Response (ITT Population) |
8.77; NA; NA | = 0.6780 |
| SECONDARY Phase II: Duration of Tumor Response in Participants With ICR PTEN Loss |
8.77; NA; NA | = 0.3173 |
| SECONDARY Phase II: Percentage of Participants With Circulating Tumor Cells (CTC) Reduction Response (ITT Population) |
67.2; 71.0; 63.5 | = 0.6652 |
| SECONDARY Phase II: Percentage of Participants With CTC Reduction Response in Participants With ICR PTEN Loss |
75.0; 75.0; 70.6 | = 0.7633 |
| SECONDARY Phase II: Percentage of Participants With CTC Conversion (ITT Population) |
43.9; 46.8; 41.7 | = 0.8317 |
| SECONDARY Phase II: Percentage of Participants With CTC Conversion in Participants With ICR PTEN Loss |
66.7; 22.2; 31.8 | = 0.0505 |
| SECONDARY Phase II: Percentage of Participants With Pain Progression (ITT Population) |
33.3; 34.9; 34.9 | — |
| SECONDARY Phase II: Percentage of Participants With Pain Progression in Participants With ICR PTEN Loss |
40.0; 28.0; 33.3 | — |
| SECONDARY Phase II: Time to Pain Progression (ITT Population) |
13.90; 16.16; 15.15 | = 0.8483 |
| SECONDARY Phase II: Time to Pain Progression in Participants With ICR PTEN Loss |
16.49; NA; 6.93 | = 0.8271 |
| SECONDARY Phase II: Percentage of Participants With Adverse Events (AEs) |
98.8; 96.6; 93.8 | — |
| SECONDARY Phase II: Ipatasertib Plasma Concentrations When Co-Administered With Abiraterone |
101; 63.4; 180; 87.0; 53.1; 24.5 | — |
| SECONDARY Phase II: G-037720 (Metabolite of Ipatasertib) Plasma Concentrations |
34.7; 13.9; 101; 42.9; 44.1; 20.4 | — |
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 /= 20 mg of prednisone per day or an equivalent dose of other anti inflammatory corticosteroids or immunosuppressant
Data sourced from ClinicalTrials.gov (NCT01485861). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.