DataVXApplied SciencesPaper
journal article·2022-05-17Open access

Evaluation and Effectiveness of Clinical Trials with Hormone Therapy in the Treatment of Prostate Cancer

Olga Ramos-Barriga, Bárbara-Yolanda Padilla-Fernández, Sebastián Valverde-Martínez, Miguel Perán-Teruel, Magaly-Teresa Márquez-Sánchez, María-Carmen Flores-Fraile, Javier Flores-Fraile, Mario Martin-Hernández, Edwin Grinard-de-León, María-Begoña García-Cenador, María-Fernanda Lorenzo-Gómez

Applied Sciences· Volume 12· Issue 10
Publisher pageOpen full text
Source abstract

Abstract

Background: Prostate cancer is currently the most common malignant tumour in men. Research on hormone therapy advances is necessary because, unfortunately, some tumours are not organ-confined. Objective: To review and analyse the current state of evidence regarding clinical trials with neoadjuvant or adjuvant hormone therapy for prostate cancer and determine the contribution of these trials to the clinical practice. Methods: A critical systematic analysis of hormone therapy clinical trials for prostate cancer in the American Society of Clinical Oncology (ASCO) 2022 official database was carried out and following the Cochrane Handbook for Systematic Reviews ofInterventions, a meta-analysis of random effects and standard mean descriptive statistics were performed. Groups: Group A = Neoadjuvant (n = 53) clinical trials and Group B = Adjuvant (n = 73) clinical hormone therapy. Variables: Phase of the trial, modality of primary treatment, investigated intervention or drug, molecular targets, trial length, sponsors and collaborators, country/countries of trial development, estimated enrolment, assignment of patients, intervention and masking model, trial purpose, related articles, the average number of studied patients, and conclusive results in clinical practice. Results: A total of 7.15% of the studies were in phase I, 14.28% between phase I-phase II, 52.38% in phase II, 0.23% between phase II-phase III and 23.80% in phase III. In the neoadjuvant group, enzalutamide and abiraterone were more frequently used, the androgen receptor was more frequently investigated as a molecular target. In the adjuvant group, abiraterone and prednisone were more frequently used and the androgen receptor and cytochrome P450 were more frequently investigated. The mean number of articles related to each trial was 5.26 (SD 3.15, 1–10). In 47.27% of the published articles directly related to the trials, the investigated treatment was superior to the standard treatment. Adjuvant investigated drugs showed more superiority (52.22%) than neoadjuvant drugs (41.33%). Conclusions: Only 41.33% of neoadjuvant studies and 52.22% of adjuvant studies show conclusive results of superiority for the proposed therapeutic strategies. About a third of related scientific publications that transfer the results to clinical practice did not report conclusive results for either neoadjuvant (32%) or adjuvant (37.78%) therapy.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Prostate Cancer Treatment and Research · Cancer, Lipids, and Metabolism · Statistical Methods in Clinical Trials

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Surgery, University of Salamanca, 37007 Salamanca, Spain

Section of Urology, Department of Surgery, University of La Laguna, 38200 Tenerife, Spain

Renal Urological Multidisciplinary Research Group (GRUMUR), The Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain

Department of Urology, University Hospital of Ávila, 05004 Ávila, Spain

Department of Urology, University Hospital Arnau de Vilanova, 46015 Valencia, Spain

Department of Urology, University Hospital of Salamanca, 37007 Salamanca, Spain

Funding

Association for the Promotion of Training and Research in Surgical Specialties in Castilla y León (APFIEQ-CyL)

References (100+)

Show source-provided references
1. Consejo de Salubridad General (2012). Prevención y Detección Temprana del Cáncer de Próstata en el Primer Nivel De Atención.
2. Lorenzo-Gómez, M.F., Fraile-Gómez, M.P., and Macías-Nuñez, J.F. (2021). Tumor de Próstata. Nefrología y Urología, Ediciones Universidad de Salamanca.10.14201/0MU0097 ↗
3. Recent Global Patterns in Prostate Cancer Incidence and Mortality Rates10.1016/j.eururo.2019.08.005 ↗
4. (2022, April 02). Cancer Today. Available online: http://gco.iarc.fr/today/home.
5. Kavoussi, L., Partin, A., Novick, A., and Peters, C. (2012). Epidemiología, Etiología y Prevención del Cáncer de Próstat. Campbell-Walsh Urología, Editorial Médica Panamericana.
6. Feltes, J., Blanco, O., and Rodríguez, A. (2007). Cáncer de próstata. Libro del Residente de Urología, Asociación Española de Urología.
7. Mottet, N., Cornford, P., van den Bergh, R., Briers, E., De Santis, M., Gillessen, S., Grivas, N., Lam, T.B., Henry, A.M., and Liwe, M. (2022). EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer, EAU Guidelines Office.
8. Prevalence of incidental prostate cancer: A systematic review of autopsy studies10.1002/ijc.29538 ↗
9. Garcia, J.G., and Cuesta, J.A. (2010). Prostatectomía radical Atlas de técnica quirúrgica. Anatomía Quirúrgica de la Próstata, Luzán.
10. Classification of prostatic carcinomas
11. The effects of castration on advanced carcinoma of the prostate gland10.1001/archsurg.1941.01210140043004 ↗
12. Factores de riesgo de cáncer de próstata: Revisión de Literatura
13. Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate10.3322/canjclin.22.4.232 ↗
14. The effect of estrogen on the sexual interest of castrated males: Implications to prostate cancer patients on androgen-deprivation therapy10.1016/j.critrevonc.2013.01.006 ↗
15. AR-V7 and prostate cancer: The watershed for treatment selection?10.1016/j.ctrv.2015.12.003 ↗
16. Development and prevalence of castration-resistant prostate cancer subtypes10.1016/j.neo.2020.09.002 ↗
17. Prior long response to androgen deprivation predicts response to next-generation androgen receptor axis targeted drugs in castration resistant prostate cancer10.1016/j.ejca.2015.06.128 ↗
18. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer10.1056/NEJMoa1911206 ↗
19. Higgins, J.P.T., and Green, S. (2015). Cochrane Handbook for Systematic Reviews of Interventions, The Cochrane Collaboration.
20. NRG Oncology (2022, April 01). A Phase II, Double-Blinded, Placebo Controlled Randomized Trial of Salvage Radiotherapy with or without Enhanced Anti-Androgen Therapy with Apalutamide in Recurrent Prostate Cancer. 2022 Mar. Report No.: NCT03371719, Available online: https://clinicaltrials.gov/ct2/show/NCT03371719.
21. Fong, L. (2022, April 01). Phase 2 Trial Pembrolizumab or Pembrolizumab in Combination with Intratumoral SD-101 Therapy in Patients with Hormone-Naïve Oligometastatic Prostate Cancer Receiving Stereotactic Body Radiation Therapy and Intermittent Androgen Deprivation Therapy. 2021 Dec. Report No.: NCT03007732, Available online: https://clinicaltrials.gov/ct2/show/NCT03007732.
22. NRG Oncology (2022, April 01). Randomized Phase II Trial of Niraparib with Standard Combination Radiotherapy and Androgen Deprivation Therapy (ADT) in High Risk Prostate Cancer (with Initial Phase I). 2022 Jan. Report No.: NCT04037254, Available online: https://clinicaltrials.gov/ct2/show/NCT04037254.
23. Canadian Cancer Trials Group (2022, April 01). Prostate Cancer Biomarker Enrichment and Treatment Selection (PC-BETS) Study. 2022 Feb. Report No.: NCT03385655, Available online: https://clinicaltrials.gov/ct2/show/NCT03385655.
24. Memorial Sloan Kettering Cancer Center (2022, April 01). ARN-509+Abiraterone Acetate+Leuprolide with Stereotactic, Ultra-Hypofractionated Radiation (AASUR) in Very High Risk Prostate Cancer: A Single Arm, Phase II Study. 2022 Feb. Report No.: NCT02772588, Available online: https://clinicaltrials.gov/ct2/show/NCT02772588.
25. Novartis Pharmaceuticals (2022, April 01). An Open-Label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination with Standard of Care, versus Standard of Care Alone, in Adult Male Patients with Metastatic Hormone Sensitive Prostate Cancer (mHSPC). 2022 Feb. Report No.: NCT04720157, Available online: https://clinicaltrials.gov/ct2/show/NCT04720157.
26. Veru Inc. (2022, April 01). VERACITY—Randomized, Active-Controlled, Phase 3 Study of VERU-111 for the Treatment of Metastatic Castration-Resistant Prostate Cancer in Patients Who Have Failed Prior Treatment with at Least One Androgen Receptor Targeting Agent. 2022 Mar. Report No.: NCT04844749, Available online: https://clinicaltrials.gov/ct2/show/NCT04844749.
27. European Organisation for Research and Treatment of Cancer—EORTC (2022, April 01). A Randomized Multicenter Phase III Trial Comparing Enzalutamide vs. a Combination of Ra223 and Enzalutamide in Asymptomatic or Mildly Symptomatic Castration Resistant Prostate Cancer Patients Metastatic to Bone. 2020 Jul. Report No.: NCT02194842, Available online: https://clinicaltrials.gov/ct2/show/NCT02194842.
28. University of Washington (2022, April 01). Radiation Enhancement of Local and Systemic Anti-Prostate Cancer Immune Responses. 2022 Mar. Report No.: NCT03649841, Available online: https://clinicaltrials.gov/ct2/show/NCT03649841.
29. AstraZeneca (2022, April 01). A Phase III Double-Blind, Randomised, Placebo-Controlled Study Assessing the Efficacy and Safety of Capivasertib+Abiraterone versus Placebo+Abiraterone as Treatment for Patients with DeNovo Metastatic Hormone-Sensitive Prostate Cancer Characterised by PTEN Deficiency. 2022 Mar. Report No.: NCT04493853, Available online: https://clinicaltrials.gov/ct2/show/NCT04493853.
30. Stanford University (2022, April 01). A Phase I/II Study of High-Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer. 2022 Feb. Report No.: NCT02346253, Available online: https://clinicaltrials.gov/ct2/show/NCT02346253.
31. M.D. Anderson Cancer Center (2022, April 01). Phase IB Study to Evaluate the Safety of Selinexor (KPT-330) in Combination with Multiple Standard Chemotherapy or Immunotherapy Agents in Patients with Advanced Malignancies. 2021 Nov. Report No.: NCT02419495, Available online: https://clinicaltrials.gov/ct2/show/NCT02419495.
32. Weill Medical College of Cornell University (2022, April 01). A Randomized Phase 2 Trial of 177Lu Radiolabeled Monoclonal Antibody HuJ591 (177Lu-J591) and Ketoconazole in Patients with High-Risk Castrate Biochemically Relapsed Prostate Cancer After Local Therapy. 2022 Mar. Report No.: NCT00859781, Available online: https://clinicaltrials.gov/ct2/show/NCT00859781.
33. Memorial Sloan Kettering Cancer Center (2022, April 01). Multi-Arm Multi-Modality Therapy for Very High Risk Localized and Low Volume Metastatic Prostatic Adenocarcinoma. 2022 Jan. Report No.: NCT03436654, Available online: https://clinicaltrials.gov/ct2/show/NCT03436654.
34. VA Office of Research and Development (2022, April 01). Systemic and Tumor-Directed Therapy for Oligometastatic Prostate Cancer. 2022 Mar. Report No.: NCT03298087, Available online: https://clinicaltrials.gov/ct2/show/NCT03298087.
35. M.D. Anderson Cancer Center (2022, April 01). Combination Treatment with Everolimus, Letrozole and Trastuzumab in Hormone Receptor and HER2/Neu-Positive Patients with Advanced Metastatic Breast Cancer and Other Solid Tumors: Evaluating Synergy and Overcoming Resistance. 2020 Dec. Report No.: NCT02152943, Available online: https://clinicaltrials.gov/ct2/show/NCT02152943.
36. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (2022, April 01). A Phase II Study of Definitive Therapy for Newly Diagnosed Men with Oligometastatic Prostate Cancer. 2021 Oct. Report No.: NCT02716974, Available online: https://clinicaltrials.gov/ct2/show/NCT02716974.
37. Janssen Research & Development, LLC (2022, April 01). A Phase 3 Randomized, Placebo-Controlled, Double-Blind Study of Niraparib in Combination with Abiraterone Acetate and Prednisone versus Abiraterone Acetate and Prednisone for the Treatment of Participants with Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC). 2022 Mar. Report No.: NCT04497844, Available online: https://clinicaltrials.gov/ct2/show/NCT04497844.
38. M.D. Anderson Cancer Center (2022, April 01). A Single Arm Study of 6-Months Neoadjuvant Apalutamide Prior to Radical Prostatectomy in Intermediate Risk Patients to Reduce the Frequency of Pathologic Features that Drive Post-Operative Radiation Therapy. 2022 Feb. Report No.: NCT03412396, Available online: https://clinicaltrials.gov/ct2/show/NCT03412396.
39. Schweizer, M. (2022, April 01). A Phase 2 Study of Apalutamide in Active Surveillance Patients. 2021 Dec. Report No.: NCT02721979, Available online: https://clinicaltrials.gov/ct2/show/NCT02721979.
40. Janssen Research & Development, LLC (2022, April 01). A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Apalutamide in Subjects with High-Risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy. 2022 Mar. Report No.: NCT03767244, Available online: https://clinicaltrials.gov/ct2/show/NCT03767244.
41. Myovant Sciences GmbH (2022, April 01). HERO: A Multinational Phase 3 Randomized, Open-Label, Parallel Group Study to Evaluate the Safety and Efficacy of Relugolix in Men with Advanced Prostate Cancer. 2022 Jan. Report No.: NCT03085095, Available online: https://clinicaltrials.gov/ct2/show/NCT03085095.
42. Henlix, Inc. (2022, April 01). A Prospective, Open-label, Dose Escalation Phase 1 Study to Investigate the Safety, and Tolerability and to Determine the Maximum Tolerated Dose and Recommended Phase 2 Dose of a HLX07, in Patients with Advanced Solid Cancers. 2019 Jul. Report No.: NCT02648490, Available online: https://clinicaltrials.gov/ct2/show/NCT02648490.
43. Montefiore Medical Center (2022, April 01). Abiraterone with Discontinuation of Gonadotropin-Releasing Hormone Analogues in Metastatic Prostate Cancer. 2021 Dec. Report No.: NCT03565835, Available online: https://clinicaltrials.gov/ct2/show/NCT03565835.
44. Butler, E.B. (2022, April 01). Phase II Study Evaluating HSV-tk + Valacyclovir Gene Therapy in Combination with Androgen Deprivation Therapy, Brachytherapy, External Beam Radiotherapy, and Prostatectomy for High-Risk Prostate Cancer. 2021 Apr. Report No.: NCT03541928, Available online: https://clinicaltrials.gov/ct2/show/NCT03541928.
45. Eli Lilly and Company (2022, April 01). A Phase 1 First-in-Human Dose Study of LY3023414 in Patients with Advanced Cancer. 2022 Jan. Report No.: NCT01655225, Available online: https://clinicaltrials.gov/ct2/show/NCT01655225.
46. Lee, H., and Moffitt Cancer Center and Research Institute (2022, April 01). Combination of Nivolumab Immunotherapy with Radiation Therapy and Androgen Deprivation Therapy in the Management of Gleason Group 5 Prostate Cancer. 2022 Jan. Report No.: NCT03543189, Available online: https://clinicaltrials.gov/ct2/show/NCT03543189.
47. Arcus Biosciences, Inc. (2022, April 01). A Phase 1b/2, Open-Label, Randomized Platform Study Evaluating the Efficacy and Safety of AB928-Based Treatment Combinations in Patients with Metastatic Castrate Resistant Prostate Cancer. 2022 Feb. Report No.: NCT04381832, Available online: https://clinicaltrials.gov/ct2/show/NCT04381832.
48. Epizyme, Inc. (2022, April 01). A Phase 1b/2 Open-Label Study Evaluating Tazemetostat in Combination with Enzalutamide or Abiraterone/Prednisone in Chemotherapy Naive Subjects with Metastatic Castration-Resistant Prostate Cancer. 2021 Dec. Report No.: NCT04179864, Available online: https://clinicaltrials.gov/ct2/show/NCT04179864.
49. Plexxikon (2022, April 01). A Multicenter, Open-Label, Parallel, Phase 1b/2a Study of PLX2853 in Combination with Abiraterone Acetate and Prednisone and Phase 1b/2a Study of PLX2853 in Combination with Olaparib in Subjects with Metastatic Castration-Resistant Prostate Cancer (mCRPC). 2021 Aug. Report No.: NCT04556617, Available online: https://clinicaltrials.gov/ct2/show/NCT04556617.
50. Bayer, A. (2022, April 01). Randomized, Open-Label, Multicenter, Phase 2b Study to Evaluate Physical Function, Including Balance and Daily Activity, in Participants with Castration-Resistant Prostate Cancer Treated with Darolutamide or Enzalutamide. 2022 Apr. Report No.: NCT04157088, Available online: https://clinicaltrials.gov/ct2/show/NCT04157088.
51. Alliance Foundation Trials, LLC (2022, April 01). A Randomized Phase II Study of Androgen Receptor Directed Therapy on Cognitive Function in Patients Treated with Darolutamide or Enzalutamide (ARACOG). 2021 Aug. Report No.: NCT04335682, Available online: https://clinicaltrials.gov/ct2/show/NCT04335682.
52. King, M. (2022, April 01). INTREPId (Intermediate Risk Erection Preservation Trial): A Randomized Trial of Radiation Therapy and Darolutamide for Prostate Cancer. 2022 Mar. Report No.: NCT04025372, Available online: https://clinicaltrials.gov/ct2/show/NCT04025372.
53. Burgess, E. (2022, April 01). A Phase II Trial of Androgen Deprivation, Docetaxel and Enzalutamide in Patients with Metastatic Hormone Sensitive Prostate Cancer. 2021 Nov. Report No.: NCT03246347, Available online: https://clinicaltrials.gov/ct2/show/NCT03246347.
54. Dahut, W. (2022, April 01). Neoadjuvant Androgen Deprivation and Enzalutamide: Using Multiparametric MRI to Evaluate Intraprostatic Tumor Responses and Androgen Resistance Patterns in Newly Diagnosed Prostate Cancer. 2021 Jun. Report No.: NCT02430480, Available online: https://clinicaltrials.gov/ct2/show/NCT02430480.
55. Aggarwal, R. (2022, April 01). A Randomized, Phase II Study of Apalutamide +/- Stereotactic Body Radiotherapy (SBRT) in Castration-Resistant Prostate Cancer Patients with Oligometastatic Disease on PSMA-PET Imaging. 2021 Aug. Report No.: NCT03503344, Available online: https://clinicaltrials.gov/ct2/show/NCT03503344.
56. Lidds, A.B. (2022, April 01). A Single Blind, Two-Stage Dose Finding Study to Evaluate the Safety, Tolerability and Efficacy of a Single Liproca® Depot Injection into the Prostate in Patients with Localized Prostate Cancer, Assigned to Active Surveillance Who Are at High Risk for Disease Progression (Followed by an Open Label Extension with a Repeat Injection (Optional)). 2020 Dec. Report No.: NCT03348527, Available online: https://clinicaltrials.gov/ct2/show/NCT03348527.
57. Pfizer (2022, April 01). Phase 1 Safety, Pharmacokinetic and Pharmacodynamic Study of Pf-02341066, A Met/Hgfr Selective Tyrosine Kinase Inhibitor, Administered Orally to Patients with Advanced Cancer. 2022 Feb. Report No.: NCT00585195, Available online: https://clinicaltrials.gov/ct2/show/NCT00585195.
58. University of Colorado, Denver (2022, April 01). An Open Label, Randomized, Phase II Trial of Metabolic Complications in Patients Treated with Enzalutamide vs Standard ADT for the Treatment of Hormone Sensitive Prostate Cancer. 2020 Jan. Report No.: NCT02278185, Available online: https://clinicaltrials.gov/ct2/show/NCT02278185.
59. Dallos, M. (2022, April 01). A Pilot Study of Neoadjuvant Non-Fucosylated Anti-CTLA-4 (BMS-986218) + Degarelix Acetate vs. Degarelix Acetate Alone in Men with High-risk Localized Prostate Cancer. 2021 Oct. Report No.: NCT04301414, Available online: https://clinicaltrials.gov/ct2/show/NCT04301414.
60. Bauman, G. (2022, April 01). Fairly Brief Androgen Suppression and Stereotactic Radiotherapy for High-Risk Prostate Cancer-Protocol 2. 2021 Jun. Report No.: NCT02229734, Available online: https://clinicaltrials.gov/ct2/show/NCT02229734.
61. Gleave, M. (2022, April 01). Genomic Biomarker-Selected Umbrella Neoadjuvant Study for High-Risk Localized Prostate Cancer. 2022 Jan. Report No.: NCT04812366, Available online: https://clinicaltrials.gov/ct2/show/NCT04812366.
62. Pfizer (2022, April 01). Talapro-3: A Phase 3, Randomized, Double-Blind, Study of Talazoparib with Enzalutamide Versus Placebo with Enzalutamide in Men with Ddr Gene Mutated Metastatic Castration-Sensitive Prostate Cancer. 2022 Mar. Report No.: NCT04821622, Available online: https://clinicaltrials.gov/ct2/show/NCT04821622.
63. Yale University (2022, April 01). SIMCAP (Surgery in Metastatic Carcinoma of Prostate): Phase 2.5 Multi-Institution Randomized Prospective Clinical Trial Evaluating the Impact of Cytoreductive Radical Prostatectomy Combined with Best Systemic Therapy on Oncologic and Quality of Life Outcomes in Men with Newly Diagnosed Metastatic Prostate Cancer. 2022 Feb. Report No.: NCT03456843, Available online: https://clinicaltrials.gov/ct2/show/NCT03456843.
64. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (2022, April 01). Combination of Bipolar Androgen Therapy and Nivolumab in Patients with Metastatic Castration-Resistant Prostate Cancer. 2021 Nov. Report No.: NCT03554317, Available online: https://clinicaltrials.gov/ct2/show/NCT03554317.
65. Veru Inc. (2022, April 01). Randomized, Double-Blind, Placebo Controlled, Dose Finding Phase 2 Study Comparing Oral Daily Dosing of VERU-944 to Ameliorate the Vasomotor Symptoms Resulting from ADT in Men with Advanced Prostate Cancer. 2021 Dec. Report No.: NCT03646162, Available online: https://clinicaltrials.gov/ct2/show/NCT03646162.
66. Progenics Pharmaceuticals, Inc. (2022, April 01). A Multicenter, Randomized, Controlled Phase 2 Study: Efficacy and Safety of I-131-1095 Radiotherapy in Combination with Enzalutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Who Are 18F-DCFPyL Prostate-specific Membrane Antigen (PSMA)-Avid, Chemotherapy-naive, and Progressed on Abiraterone. 2021 Sep. Report No.: NCT03939689, Available online: https://clinicaltrials.gov/ct2/show/NCT03939689.
67. Fong, L. (2022, April 01). An Open-Label Multi-Center Phase II Study of Neoadjuvant Atezolizumab-Based Combination Therapy in Men with Localized Prostate Cancer Prior to Radical Prostatectomy. 2022 Feb. Report No.: NCT03821246, Available online: https://clinicaltrials.gov/ct2/show/NCT03821246.
68. Proton Collaborative Group (2022, April 01). Phase III Study of Image Guided Radiation Therapy with or without Androgen Suppression for Intermediate Risk Adenocarcinoma of the Prostate. 2021 Oct. Report No.: NCT01492972, Available online: https://clinicaltrials.gov/ct2/show/NCT01492972.
69. Merck Sharp & Dohme Corp (2022, April 01). A Phase 3, Randomized, Double-Blind Trial of Pembrolizumab (MK-3475) Plus Enzalutamide versus Placebo Plus Enzalutamide in Participants with Metastatic Castration-Resistant Prostate Cancer (mCRPC) (KEYNOTE-641). 2022 Apr. Report No.: NCT03834493, Available online: https://clinicaltrials.gov/ct2/show/NCT03834493.
70. Solanki, A.A. (2022, April 01). BEACON—A Phase I/II Study of High-Dose-Rate Brachytherapy and External Beam and Short-Term Androgen Deprivation Combined for the Treatment of Men with Fluciclovine PET Pelvic Nodal Uptake in Locally Recurrent Prostate Cancer After Prior Definitive Radiotherapy. 2020 May. Report No.: NCT03553602, Available online: https://clinicaltrials.gov/ct2/show/NCT03553602.
71. Sunnybrook Health Sciences Centre (2022, April 01). Intermittent Androgen Deprivation Therapy with or without Stereotactic Body Radiotherapy for Molecularly Identified Hormone Sensitive Oligometastatic Prostate Cancer: A Randomized Feasibility Study. 2020 Dec. Report No.: NCT04619069, Available online: https://clinicaltrials.gov/ct2/show/NCT04619069.
72. Ornstein, M. (2022, April 01). The Association Between HSD3B1 Genotype and Steroid Metabolism in Normal and Prostate Cancer Tissue of Men with Intermediate and High-Risk Prostate Cancer Undergoing Radical Prostatectomy After Treatment with Apalutamide and Leuprolide. 2021 Mar. Report No.: NCT02770391, Available online: https://clinicaltrials.gov/ct2/show/NCT02770391.
73. Aggarwal, R. (2022, April 01). A Phase 1b/2 Study of the Oral CDK4/6 Inhibitor LEE011 (Ribociclib) in Combination with Docetaxel Plus Prednisone in Metastatic Castration Resistant Prostate Cancer. 2021 Oct. Report No.: NCT02494921, Available online: https://clinicaltrials.gov/ct2/show/NCT02494921.
74. Sidney Kimmel Cancer Center at Thomas Jefferson University (2022, April 01). Randomized Phase IB/II Study of Enzalutamide with and Without Ribociclib in Patients with Metastatic Castrate Resistant, Chemotherapy Naïve Prostate Cancer That Retains RB Expression. 2021 Aug. Report No.: NCT02555189, Available online: https://clinicaltrials.gov/ct2/show/NCT02555189.
75. Zenith Epigenetics (2022, April 01). A Phase 1b/2a Safety and Tolerability Study of ZEN003694 in Combination with Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer. 2021 Nov. Report No.: NCT02711956, Available online: https://clinicaltrials.gov/ct2/show/NCT02711956.
76. Taiho Oncology, Inc. (2022, April 01). A Phase 1, Open-Label, Non-Randomized, Safety, Tolerability and Pharmacokinetic Study of TAS3681 in Patients with Metastatic Castration Resistant Prostate Cancer. 2022 Jan. Report No.: NCT02566772, Available online: https://clinicaltrials.gov/ct2/show/NCT02566772.
77. Weill Medical College of Cornell University (2022, April 01). Phase I/II Trial of Pembrolizumab and Androgen-Receptor Pathway Inhibitor with or without 225Ac-J591 for Progressive Metastatic Castration Resistant Prostate Cancer. 2021 Sep. Report No.: NCT04946370, Available online: https://clinicaltrials.gov/ct2/show/NCT04946370.
78. M.D. Anderson Cancer Center (2022, April 01). A Pre-Operative Study to Assess the Effects of Apalutamide Plus LHRH Agonist or Apalutamide Plus Abiraterone Acetate Plus LHRH Agonist for Six Months for Prostate Cancer Patients at High Risk for Recurrence. 2021 May. Report No.: NCT03279250, Available online: https://clinicaltrials.gov/ct2/show/NCT03279250.
79. Hussain, M. (2022, April 01). BRCAAway: A Randomized Phase II Trial of Abiraterone, Olaparib, or Abiraterone + Olaparib in Patients with Metastatic Castration-Resistant Prostate Cancer with DNA Repair Defects. 2021 Mar. Report No.: NCT03012321, Available online: https://clinicaltrials.gov/ct2/show/NCT03012321.
80. University Health Network, Toronto (2022, April 01). Anti-Androgens and Cabazitaxel in Defining Complete Response in Prostatectomy (ACDC-RP Trial): A Randomized, Open-Label, Multi-Centre Phase-2 Study Evaluating the Pathological Complete Response (pCR) Rate Following Neoadjuvant Therapy in Participants with High-Risk Prostate Carcinoma for Whom Radical Prostatectomy Is Indicated. 2021 Oct. Report No.: NCT02543255, Available online: https://clinicaltrials.gov/ct2/show/NCT02543255.
81. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (2022, April 06). A Randomized Phase II Study Comparing Sequential High Dose Testosterone and Enzalutamide to Enzalutamide Alone in Asymptomatic Men with Castration Resistant Metastatic Prostate Cancer. 2022 Feb. Report No.: NCT04363164, Available online: https://clinicaltrials.gov/ct2/show/NCT04363164.
82. ECOG-ACRIN Cancer Research Group (2022, April 01). Cabazitaxel with Abiraterone versus Abiraterone Alone Randomized Trial for Extensive Disease Following Docetaxel: The CHAARTED2 Trial. 2021 Dec. Report No.: NCT03419234, Available online: https://clinicaltrials.gov/ct2/show/NCT03419234.
83. Hoffmann-La Roche (2022, April 01). A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial Testing Ipatasertib Plus Abiraterone Plus Prednisone/Prednisolone, Relative to Placebo Plus Abiraterone Plus Prednisone/Prednisolone in Adult Male Patients with Asymptomatic or Mildly Symptomatic, Previously Untreated, Metastatic Castrate-Resistant Prostate Cancer. 2022 Apr. Report No.: NCT03072238, Available online: https://clinicaltrials.gov/ct2/show/NCT03072238.
84. AstraZeneca (2022, April 01). A Randomised, Double-Blind, Placebo-Controlled, Multicentre Phase III Study of Olaparib Plus Abiraterone Relative to Placebo Plus Abiraterone as First-Line Therapy in Men with Metastatic Castration-Resistant Prostate Cancer (PROpel Study). 2022 Apr. Report No.: NCT03732820, Available online: https://clinicaltrials.gov/ct2/show/NCT03732820.
85. M.D. Anderson Cancer Center (2022, April 01). A Dynamic Allocation Modular Sequential Trial of Approved and Promising Therapies in Men with Metastatic Castrate Resistant Prostate Cancer. 2022 Feb. Report No.: NCT02703623, Available online: https://clinicaltrials.gov/ct2/show/NCT02703623.
86. M.D. Anderson Cancer Center (2022, April 01). A Phase 2, Study of Apalutamide and Abiraterone Acetate in Castration-Resistant Metastatic Prostate Cancer Patients Evaluating a Predetermined Biomarker Signature. 2021 Feb. Report No.: NCT03360721, Available online: https://clinicaltrials.gov/ct2/show/NCT03360721.
87. Kim, I.Y. (2022, April 01). Randomized Three-Arm Trial to Evaluate the Effect of Neoadjuvant Apalutamide Alone or in Combination with Abiraterone Acetate and GnRH Agonist on Enhancing Surgical Outcome of Nerve-Sparing Radical Prostatectomy in Men with High-Risk Prostate Cancer. 2021 Apr. Report No.: NCT02949284, Available online: https://clinicaltrials.gov/ct2/show/NCT02949284.
88. Harshman, L.C. (2022, April 01). A Phase 2 Study of Docetaxel Plus Apalutamide in Castration-Resistant Prostate Cancer Patients post Abiraterone Acetate. 2020 Apr. Report No.: NCT03093272, Available online: https://clinicaltrials.gov/ct2/show/NCT03093272.
89. D’Amico, A.V. (2022, April 01). A Randomized Phase III Study–Conventional Androgen Deprivation Therapy with or without Abiraterone Acetate + Prednisone and Apalutamide Following a Detectable PSA after Radiation and Androgen Deprivation Therapy. 2021 Nov. Report No.: NCT03777982, Available online: https://clinicaltrials.gov/ct2/show/NCT03777982.
90. Ngyuen, P. (2022, April 01). Randomized Phase II Study of Salvage XRT + ADT +/- Abiraterone Acetate and Apalutamide (ARN-509) for Rising PSA after Radical Prostatectomy with Adverse Features. (FORMULA-509 Trial). 2022 Mar. Report No.: NCT03141671, Available online: https://clinicaltrials.gov/ct2/show/NCT03141671.
91. Amgen (2022, April 01). A Master Protocol Evaluating the Safety and Efficacy of Therapies for Metastatic Castration-Resistant Prostate Cancer (mCRPC). 2022 Mar. Report No.: NCT04631601, Available online: https://clinicaltrials.gov/ct2/show/NCT04631601.
92. Memorial Sloan Kettering Cancer Center (2022, April 01). An Exploratory Randomized Phase II Multicenter Trial of Abiraterone Acetate with or without Cabazitaxel in Treatment of Metastatic Castration Resistant Prostate Cancer. 2021 Sep. Report No.: NCT02218606, Available online: https://clinicaltrials.gov/ct2/show/NCT02218606.
93. Southwest Oncology Group (2022, April 01). Phase III Randomized Trial of Standard Systemic Therapy (SST) versus Standard Systemic Therapy Plus Definitive Treatment (Surgery or Radiation) of the Primary Tumor in Metastatic Prostate Cancer. 2021 Nov. Report No.: NCT03678025, Available online: https://clinicaltrials.gov/ct2/show/NCT03678025.
94. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (2022, April 01). Randomized Trial Assessing Induction of Double Strand Breaks with Androgen Receptor Partial Agonist in Patients on Androgen Suppression. 2021 Sep. Report No.: NCT03507608, Available online: https://clinicaltrials.gov/ct2/show/NCT03507608.
95. M.D. Anderson Cancer Center (2022, April 01). Randomized Phase II Study of Olaparib Maintenance Following Cabazitaxel-Carboplatin Induction Chemotherapy in Men with Aggressive Variant Prostate Cancer (AVPC). 2021 Apr. Report No.: NCT03263650, Available online: https://clinicaltrials.gov/ct2/show/NCT03263650.
96. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (2022, April 01). Overcoming Drug Resistance in Metastatic Castration-Resistant Prostate Cancer with Novel Combination of TGF-β Receptor Inhibitor LY2157299 and Enzalutamide: A Randomized Multi-Site Phase II Study. 2022 Jan. Report No.: NCT02452008, Available online: https://clinicaltrials.gov/ct2/show/NCT02452008.
97. Fox Chase Cancer Center (2022, April 01). Bicalutamide with or without Metformin for Biochemical Recurrence in Overweight or Obese Prostate Cancer Patients (BIMET-1). 2022 Mar. Report No.: NCT02614859, Available online: https://clinicaltrials.gov/ct2/show/NCT02614859.
98. Parikh, M. (2022, April 01). A Phase II Study with a Lead-In Safety Phase of Abiraterone in Combination with PDMX1001/Niclosamide in Castration-Resistant Prostate Cancer (CRPC). 2022 Feb. Report No.: NCT02807805, Available online: https://clinicaltrials.gov/ct2/show/NCT02807805.
99. Cardiff Oncology (2022, April 01). A Phase 2 Study of PCM-075 (Onvansertib) in Combination with Abiraterone and Prednisone in Adult Patients with Metastatic Castration-Resistant Prostate Cancer. 2021 Mar. Report No.: NCT03414034, Available online: https://clinicaltrials.gov/ct2/show/NCT03414034.
100. Eli Lilly and Company (2022, April 01). A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study of Abiraterone Acetate Plus Prednisone with or without Abemaciclib in Patients with Metastatic Castration-Resistant Prostate Cancer. 2022 Mar. Report No.: NCT03706365, Available online: https://clinicaltrials.gov/ct2/show/NCT03706365.