Randomized Salvage Radiation Therapy Plus Enzalutamide Post Prostatectomy
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|ClinicalTrials.gov Identifier: NCT02203695|
Recruitment Status : Active, not recruiting
First Posted : July 30, 2014
Last Update Posted : September 2, 2020
|Condition or disease||Intervention/treatment||Phase|
|Adenocarcinoma of the Prostate||Drug: Enzalutamide Radiation: SRT||Phase 2|
Enzalutamide is a second-generation androgen receptor signaling inhibitor that significantly prolongs survival in patients with metastatic castration-resistant prostate cancer who have received prior docetaxel chemotherapy 35,36. Enzalutamide has demonstrated activity in cells that overexpress the androgen receptor. Unlike previous androgen receptor blocker (ARB) agents, Enzalutamide does not display any agonist properties and blocks translocation of the ligand-receptor complex into the nucleus preventing DNA binding 33. Enzalutamide is an oral agent that is generally well tolerated and does not require concurrent steroid administration, which makes it an ideal candidate for combination with salvage radiation therapy (SRT).
Finally, provocative preliminary Phase II data presented at the American Society of Clinical Oncology (ASCO) 2013 by M. Smith and colleagues assessed the efficacy and safety of 25-weeks (~6-mos) of enzalutamide alone in prostate cancer of all stages who had never received hormone therapy; presenting with non-castrate testosterone levels ( 230 ng/dL). Enzalutamide alone for 6-mos achieved a high PSA response rate with efficacy similar to castration, but .in contrast to castration, bone mineral density (BMD) remained stable and metabolic variables were not substantially impacted.
The trial described here differs from Radiation Therapy Oncology Group (RTOG) 96-01, RTOG 05-34 and RADICALS in several ways. First, the eligibility criteria are stricter; less favorable patients have been selected. Second, short-term ARB is being tested, while in RTOG 96-01 and RADICALS long-term ARB of 2-years was examined. Finally, and most importantly, we are testing the second generation ARB agent, enzalutamide, alone in combination with SRT as opposed to RTOG 05-34 and RADICALS which use androgen deprivation (AD).
This trial is not intended to address the efficacy of SRT alone over observation. The complete response rate (a drop in PSA to undetectable levels) after SRT is 70%-80% and durable responses are observed in 30%-40% of patients. For these reasons, it is not feasible or appropriate to randomize men between observation and SRT. The more important issue is whether the proportion of durable responses is increased by altering the therapeutic approach, such as the use of enhanced ARB using enzalutamide.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||122 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||Phase II Randomized Placebo-Controlled Double-Blind Study of Salvage Radiation Therapy (SRT) Plus Placebo Versus SRT Plus Enzalutamide in Men With High-Risk PSA-Recurrent Prostate Cancer After Radical Prostatectomy|
|Actual Study Start Date :||March 28, 2015|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||January 10, 2023|
Experimental: SRT plus Enzalutamide
Arm 2 (experimental): (SRT) Salvage radiation therapy (Three dimensional conformal radiation therapy (3D-CRT)/IMRT [Intensity-modulated radiation therapy]) 66.6-70.2 Gy as 1.8 Gy M-F for 37-39 fx PLUS Enzalutamide (MDV3100) 160 mg PO once daily for 6 months (2 months prior to SRT, 2 months during SRT and 2 months following SRT)
Enzalutamide (MDV3100) 160 mg PO once daily for 6 months (2 months prior to SRT, 2 months during SRT and 2 months following SRT)
Other Name: XTANDI
Placebo Comparator: SRT plus placebo
Arm 1 (control): Salvage radiation therapy (3D-CRT (Three dimensional conformal radiation therapy)/IMRT (Intensity-modulated radiation therapy)) 66.6-70.2 Gy given 1.8 Gy M-F for 37 -39 fx PLUS Placebo PO daily for 6 months (2 months prior to SRT, 2 months during SRT and 2 months following SRT)
Salvage radiation therapy (3D-CRT (Three dimensional conformal radiation therapy)/IMRT) 66.6-70.2 Gy given 1.8 Gy M-F for 37 -39 fx
Other Name: Salvage Radiation Therapy
- Freedom of PSA (Prostate Specific Antigen) progression [ Time Frame: 2 years from end of therapy ]The primary efficacy endpoint is the rate of Freedom-from-PSA-progression (FFPP) at 2-years. FFPP is defined as the time from randomization to the date of PSA progression. A subject who does not have PSA progression at the time of the analysis will be censored at the last date of PSA measurement.
- Local recurrence [ Time Frame: 2 years from end of therapy ]Local recurrence within the radiation field (confirmed pathologically) at 2-years
- Metastatic free survival rate [ Time Frame: 2 years from the time of registration ]Metastasis-free survival (MFS) rates at 2 years. Metastasis-free survival will be defined as the time from the date of registration to date of evidence of systemic disease on bone scan or cross sectional imaging or death, which occurs first.
- Adverse Events Encountered [ Time Frame: At the end of therapy at months 2, 3, 4, 5, 6 and then every 3 months for 24 months ]Safety as assessed by NCI Common Toxicity Scales (v4.0)
- How well participants tolerate treatment [ Time Frame: During active treatment phase of study, at the end of therapy at months 2, 3, 4, 5, 6 and then every 3 months for 24 months ]Quality of life (QoL) tools to be used to determine participant tolerability of treatment will include FACT-P, European Organization for the Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) -C30/QLQ-PR25, and SHIM.
- Feasibility of achieving stated accrual [ Time Frame: During active treatment phase of study, at the end of therapy at months 2, 3, 4, 5, 6 and then every 3 months for 24 months ]Compare anticipated accrual versus actual.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02203695
|United States, District of Columbia|
|Sibley Memorial Hospital|
|Washington, District of Columbia, United States, 20016|
|United States, Illinois|
|University of Chicago Medical Center|
|Chicago, Illinois, United States, 60637|
|United States, Indiana|
|Lafayette, Indiana, United States, 47904|
|United States, Maryland|
|The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21287|
|Bethesda, Maryland, United States, 20814|
|United States, Michigan|
|University of Michigan Health System|
|Ann Arbor, Michigan, United States, 48109|
|Karmanos Cancer Center|
|Detroit, Michigan, United States, 48201|
|United States, Oregon|
|Oregon Health Sciences University|
|Portland, Oregon, United States, 97239|
|United States, Utah|
|University of Utah - Huntsman Cancer Center|
|Salt Lake City, Utah, United States, 84112|
|Principal Investigator:||Phuoc Tran, M.D.||The SKCCC at Johns Hopkins|