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| ID | Type | Description | Link |
|---|---|---|---|
| IRB00030471 | Other Identifier | JHMIRB |
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| Name | Class |
|---|---|
| Astellas Pharma Inc | INDUSTRY |
| Medivation, Inc. | INDUSTRY |
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The primary hypothesis of this study is that outcomes for patients with biochemically recurrent prostate cancer following radical prostatectomy will be improved by the addition of enzalutamide for 6-months compared to standard-of-care salvage radiation therapy to allow for further study in the definitive phase III setting. This study builds on the prior success of high-dose bicalutamide (for 24 months) when combined with salvage external radiation therapy (XRT), while using a newer more potent anti-androgen for a shorter duration of time (6 months) in an effort to minimize adverse effects.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SRT plus Enzalutamide | Experimental | 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) |
|
| SRT plus placebo | Placebo Comparator | 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Enzalutamide | Drug | Enzalutamide (MDV3100) 160 mg PO once daily for 6 months (2 months prior to SRT, 2 months during SRT and 2 months following SRT) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent of Participants With Freedom of PSA (Prostate Specific Antigen) Progression | 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. | From time of randomization to date of PSA progression, approximately 2 years. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Local Recurrence | Local recurrence within the radiation field (confirmed pathologically) at 2-years | 2 years from end of radiation therapy |
| Metastatic Free Survival Rate |
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Inclusion Criteria:
Exclusion Criteria:
Currently active second malignancy
Primary treatment with radiation therapy.
Radiographic or clinical evidence of local-regional tumor recurrence,
Concurrent use of other antiandrogens, estrogen-like agents, or 5a-reductase inhibitors.
Use of systemic corticosteroids equivalent to prednisone (inhaled corticosteroids are permitted).
Concurrent use of other anti-cancer agents or treatments.
Serious concurrent medical illnesses (including uncontrolled major cardiac, pulmonary, Child-Pugh C liver or psychiatric diseases) or active major infections (including HIV, Hepatitis A-C).
Clinically significant cardiovascular disease including:
Medications which lowers seizure threshold.
History of seizure or any condition that may predispose to seizure including, but not limited to underlying brain injury, stroke, primary brain tumors, brain metastases, or alcoholism. Also, history of loss of consciousness or transient ischemic attack within 12months of enrollment (Day 1 visit).
Patients taking medications that may have adverse interactions with enzalutamide
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| Name | Affiliation | Role |
|---|---|---|
| Daniel Song, M.D. | The SKCCC at Johns Hopkins | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sibley Memorial Hospital | Washington D.C. | District of Columbia | 20016 | United States | ||
| University of Chicago Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36367998 | Derived | Tran PT, Lowe K, Tsai HL, Song DY, Hung AY, Hearn JWD, Miller S, Proudfoot JA, Deek MP, Phillips R, Lotan T, Paller CJ, Marshall CH, Markowski M, Dipasquale S, Denmeade S, Carducci M, Eisenberger M, DeWeese TL, Orton M, Deville C, Davicioni E, Liauw SL, Heath EI, Greco S, Desai NB, Spratt DE, Feng F, Wang H, Beer TM, Antonarakis ES. Phase II Randomized Study of Salvage Radiation Therapy Plus Enzalutamide or Placebo for High-Risk Prostate-Specific Antigen Recurrent Prostate Cancer After Radical Prostatectomy: The SALV-ENZA Trial. J Clin Oncol. 2023 Feb 20;41(6):1307-1317. doi: 10.1200/JCO.22.01662. Epub 2022 Nov 11. | |
| 31196032 |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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: Enzalutamide (MDV3100) 160 mg PO once daily for 6 months (2 months prior to SRT, 2 months during SRT and 2 months following SRT) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 15, 2022 |
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| SRT | Radiation | 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 |
|
|
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. Number of participants with a metastasis event at 2 years is reported.
| 2 years from the time of registration |
| How Well Participants Tolerate Treatment Assessed by European Organization for Research & Treatment of Cancer Quality of Life (Questionnaire (EORTC-QLQ-P25) | The European Organization for the Research and Treatment of Cancer (EORTC-QLQ-P25) quality of life questionnaire, Prostate Cancer Module. Uses a 4-point Likert scale, with responses ranging from "not at all" to "very much" for sexual symptoms and treatment related symptoms. Domain scores range 0 to 100, with higher scores reflecting either more symptoms (urinary, bowel, hormonal treatment-related symptoms) or higher levels of activity or functioning (sexual). | Baseline, End of Treatment (180 Days) and 6 Months Post-treatment |
| How Well Participants Tolerate Treatment Assessed by the Functional Assessment of Cancer Therapy-Prostate (FACT-P). | The Functional Assessment of Cancer Therapy (FACT-P), assesses the health-related quality of life in men with prostate cancer. The score is the sum of all 5 domain scores and ranges from 0 to156 where higher scores represent better quality of life. | Baseline, End of Treatment (180 Days) and 6 Months Post-treatment |
| How Well Participants Tolerate Treatment Assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). | European Organization for Research and Treatment of Cancer Quality of Life Questionnaire score range is from 0 to 100. A higher score indicates a better level of functioning or quality of life. | Baseline, End of Treatment (180 Days) and 6 Months Post-treatment |
| How Well Participants Tolerate Treatment Assessed by Sexual Health Inventory in Men (SHIM) Questionnaire. | Quality of life (QoL) tool used to determine participant tolerability of treatment assessed by Sexual Health inventory in Men (SHIM). The questionnaire includes 5-items, and provides a total score from 1 to 25, with higher scores indicating better erectile function and lower scores indicating more severe erectile dysfunction. | Baseline, End of Treatment (180 Days) and 6 Months Post-treatment |
| Feasibility of Achieving Stated Accrual | Anticipated accrual of participants versus actual reported enrollment. The goal is 48 in each arm. | 2 years |
| Chicago |
| Illinois |
| 60637 |
| United States |
| Indiana University | Lafayette | Indiana | 47904 | United States |
| The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland | 21287 | United States |
| Suburban Hospital | Bethesda | Maryland | 20814 | United States |
| University of Michigan Health System | Ann Arbor | Michigan | 48109 | United States |
| Karmanos Cancer Center | Detroit | Michigan | 48201 | United States |
| Oregon Health Sciences University | Portland | Oregon | 97239 | United States |
| University of Utah - Huntsman Cancer Center | Salt Lake City | Utah | 84112 | United States |
| Derived |
| Kapoor R, Deek MP, McIntyre R, Raman N, Kummerlowe M, Chen I, Gaver M, Wang H, Denmeade S, Lotan T, Paller C, Markowski M, Carducci M, Eisenberger M, Beer TM, Song DY, DeWeese TL, Hearn JW, Greco S, DeVille C, Desai NB, Heath EI, Liauw S, Spratt DE, Hung AY, Antonarakis ES, Tran PT. A phase II randomized placebo-controlled double-blind study of salvage radiation therapy plus placebo versus SRT plus enzalutamide with high-risk PSA-recurrent prostate cancer after radical prostatectomy (SALV-ENZA). BMC Cancer. 2019 Jun 13;19(1):572. doi: 10.1186/s12885-019-5805-z. |
| FG001 | 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) 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 |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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: Enzalutamide (MDV3100) 160 mg PO once daily for 6 months (2 months prior to SRT, 2 months during SRT and 2 months following SRT) |
| BG001 | 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) 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 |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent of Participants With Freedom of PSA (Prostate Specific Antigen) Progression | 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. | Posted | Number | Percent of patients with no progession | From time of randomization to date of PSA progression, approximately 2 years. |
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| ||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Local Recurrence | Local recurrence within the radiation field (confirmed pathologically) at 2-years | Posted | Number | Participants with local recurrence | 2 years from end of radiation therapy |
|
| |||||||||||||||||||||||||||||||
| Secondary | Metastatic Free Survival Rate | 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. Number of participants with a metastasis event at 2 years is reported. | Posted | Number | participants | 2 years from the time of registration |
| ||||||||||||||||||||||||||||||||
| Secondary | How Well Participants Tolerate Treatment Assessed by European Organization for Research & Treatment of Cancer Quality of Life (Questionnaire (EORTC-QLQ-P25) | The European Organization for the Research and Treatment of Cancer (EORTC-QLQ-P25) quality of life questionnaire, Prostate Cancer Module. Uses a 4-point Likert scale, with responses ranging from "not at all" to "very much" for sexual symptoms and treatment related symptoms. Domain scores range 0 to 100, with higher scores reflecting either more symptoms (urinary, bowel, hormonal treatment-related symptoms) or higher levels of activity or functioning (sexual). | Participants with data collected | Posted | Mean | Standard Deviation | score on a scale | Baseline, End of Treatment (180 Days) and 6 Months Post-treatment |
| ||||||||||||||||||||||||||||||
| Secondary | How Well Participants Tolerate Treatment Assessed by the Functional Assessment of Cancer Therapy-Prostate (FACT-P). | The Functional Assessment of Cancer Therapy (FACT-P), assesses the health-related quality of life in men with prostate cancer. The score is the sum of all 5 domain scores and ranges from 0 to156 where higher scores represent better quality of life. | Participants with data collected | Posted | Mean | Standard Deviation | score on a scale | Baseline, End of Treatment (180 Days) and 6 Months Post-treatment |
| ||||||||||||||||||||||||||||||
| Secondary | How Well Participants Tolerate Treatment Assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). | European Organization for Research and Treatment of Cancer Quality of Life Questionnaire score range is from 0 to 100. A higher score indicates a better level of functioning or quality of life. | Participants with data collected | Posted | Mean | Standard Deviation | score on a scale | Baseline, End of Treatment (180 Days) and 6 Months Post-treatment |
| ||||||||||||||||||||||||||||||
| Secondary | How Well Participants Tolerate Treatment Assessed by Sexual Health Inventory in Men (SHIM) Questionnaire. | Quality of life (QoL) tool used to determine participant tolerability of treatment assessed by Sexual Health inventory in Men (SHIM). The questionnaire includes 5-items, and provides a total score from 1 to 25, with higher scores indicating better erectile function and lower scores indicating more severe erectile dysfunction. | Participants with data collected | Posted | Mean | Standard Deviation | score on a scale | Baseline, End of Treatment (180 Days) and 6 Months Post-treatment |
| ||||||||||||||||||||||||||||||
| Secondary | Feasibility of Achieving Stated Accrual | Anticipated accrual of participants versus actual reported enrollment. The goal is 48 in each arm. | The Overall Number of Participants analyzed represents the goal of 48 participants in each arm. | Posted | Count of Participants | Participants | 2 years |
|
Up to 2 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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: Enzalutamide (MDV3100) 160 mg PO once daily for 6 months (2 months prior to SRT, 2 months during SRT and 2 months following SRT) | 2 | 43 | 0 | 43 | 43 | 43 |
| EG001 | 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) 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 | 0 | 43 | 0 | 43 | 43 | 43 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| nocturia | Nervous system disorders | Systematic Assessment |
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| lymphopenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Back Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| erectile dysfunction | Nervous system disorders | Systematic Assessment |
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| hypertension | General disorders | Systematic Assessment |
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| fall | General disorders | Systematic Assessment |
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| humerus fracture | General disorders | Systematic Assessment |
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| fatigue | General disorders | Systematic Assessment |
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| urinary frequency/urgency | Renal and urinary disorders | Systematic Assessment |
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| diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| breast and nipple pain | General disorders | Systematic Assessment |
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| sexuality alteration | General disorders | Systematic Assessment |
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| urinary incontinence | Renal and urinary disorders | Systematic Assessment |
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| Anorexia | Psychiatric disorders | Systematic Assessment |
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| hemmorrhoids | Gastrointestinal disorders | Systematic Assessment |
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| hot flashes | Endocrine disorders | Systematic Assessment |
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| hyperglycemia | Endocrine disorders | Systematic Assessment |
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| nausea | Gastrointestinal disorders | Systematic Assessment |
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| pain (due to XRT) | General disorders | Systematic Assessment |
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| Proctitis | General disorders | Systematic Assessment |
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| Urinary Retention | Renal and urinary disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Daniel Song | Johns Hopkins University, School of Medicine | 410-502-5875 | dsong2@jh.edu |
| Jan 11, 2024 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| C540278 | enzalutamide |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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