Table 2.
Clinical Trials for Targeted Therapies in Prostate Cancer
| Target | Ongoing Trials | Therapies | ClinicalTrials.gov Identifier | Genome-Based Enrichment or Randomization |
|---|---|---|---|---|
| ETS fusions | Study combining ABT-888, oral PARP inhibitor, with temozolomide in patients with metastatic prostate cancer | ABT-888, PARP inhibitor | NCT01085422 | ETS randomization |
| Study to assess safety and tolerability of oral CC-115 for patients with advanced solid tumors, non-Hodgkin lymphoma, or multiple myeloma | CC-115, DNAPK, and mTOR inhibitor | NCT01353625 | None | |
| Abiraterone acetate with or without veliparib in treating patients with metastatic prostate cancer | Veliparib, PARP inhibitor | NCT01576172 | None | |
| PI3K/mTOR/AKT pathway | Phase II study of BKM120 in men with metastatic CRPC | BKM120, PI3K inhibitor | NCT01385293 | None |
| Phase I/IIa, first time in human study of GSK2636771 in patients with advanced solid tumors with PTEN deficiency | GSK2636771, PI3K inhibitor | NCT01458067 | PTEN deficiency by immunohistochemistry | |
| Phase II study of the efficacy and safety of AP23573 in patients with taxane-resistant AIPC | Ridaforolimus, mTOR inhibitor | NCT00110188 | None | |
| Temsirolimus to reverse androgen insensitivity for CRPC | Temsirolimus, mTOR inhibitor | NCT01020305 | None | |
| Androgen signaling | Determine effect of MDV3100 on androgen signaling pathway in correlation with anti-tumor effects of MDV3100 to identify potential predictors of response or resistance to therapy | MDV3100, second-generation AR antagonist | NCT01091103 | None |
| Safety and efficacy study of MDV3100 in patients with CRPC who have been previously treated with docetaxel-based chemotherapy (AFFIRM)46 | MDV3100, second-generation AR antagonist | NCT00974311 | None | |
| Safety, pharmacokinetic and proof-of-concept study of ARN-509 in CRPC | ARN 509, second-generation AR antagonist | NCT01171898 | None | |
| Combinations | Bicalutamide with or without MK2206 in treating patients with previously treated prostate cancer | Bicalutamide plus MK2206, AKT inhibitor | NCT01251861 | None |
| Temsirolimus to reverse androgen insensitivity for CRPC | Temsirolimus (mTOR) | NCT01020305 | None | |
| Study of GDC-0068 or GDC-0980 with abiraterone acetate versus abiraterone acetate in patients with CRPC previously treated with docetaxel chemotherapy | Abiraterone plus GDC-0068 (AKT inhibitor) or GDC-0980 (PI3K/mTOR inhibitor) | NCT01485861 | None | |
| Private driver mutations | Abiraterone acetate with or without veliparib in treating patients with metastatic prostate cancer | Vemurafenib, RAF inhibitor | NCT01085422 | BRAF subset receives vemurafenib |
NOTE. There are multiple ongoing trials involving novel agents targeting ETS, PI3K pathway, and AR signaling in prostate cancer. Few studies are beginning to target multiple pathways through combination therapies. Although this table is not comprehensive, it is meant to provide an overview of directions for targeted therapies in prostate cancer.
Abbreviations: AFFIRM, A Study Evaluating the Efficacy and Safety of the Investigational Drug MDV3100; AIPC, androgen-independent prostate cancer; AR, androgen receptor; CRPC, castration-resistant prostate cancer; mTOR, mammalian target of rapamycin; PARP, poly (ADP-ribose) polymerase; PI3K, phosphatidylinositide 3-kinase; PTEN, phosphatase and tensin homolog.