Testing the Addition of the Drug Relugolix to the Usual Radiation Therapy for Advanced-Stage Prostate Cancer, The NRG Promethean Study

Phase 2

Recruiting

• Conditions: Oligometastatic Prostate Carcinoma; Prostate Adenocarcinoma; Prostate Ductal Adenocarcinoma; Prostate Intraductal Carcinoma; Stage IVB Prostate Cancer AJCC v8
• Interventions: Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Other: Fluciclovine F18; Procedure: Magnetic Resonance Imaging; Drug: Placebo Administration; Procedure: Positron Emission Tomography; Procedure: PSMA PET Scan; Other: Quality-of-Life Assessment; Drug: Relugolix; Radiation: Stereotactic Body Radiation Therapy

• Registration Number: NCT05053152
• Lead Sponsor: NRG Oncology

Brief Summary

This phase II trial compares the usual treatment of radiation therapy alone to using the study drug, relugolix, plus the usual radiation therapy in patients with castration-sensitive prostate cancer that has spread to limited other parts of the body (oligometastatic). Relugolix is in a class of medications called gonadotropin-releasing hormone (GnRH) receptor antagonists. It works by decreasing the amount of testosterone (a male hormone) produced by the body. It may stop the growth of cancer cells that need testosterone to grow. Radiation therapy uses high-energy x rays or protons to kill tumor cells. The addition of relugolix to the radiation may reduce the chance of oligometastatic prostate cancer spreading further.

Detailed Description

PRIMARY OBJECTIVE:

I. Compare conventional radiological progression-free survival (rPFS) for positron emission tomography (PET)-detected, biochemically recurrent, oligometastatic, castration-sensitive prostate cancer patients treated with stereotactic ablative body radiation therapy (SABR) plus placebo versus (vs.) SABR plus relugolix.

SECONDARY OBJECTIVES:

I. Compare conventional or PET-based radiological progression-free survival (prPFS) between treatment arms.

II. Compare patient-reported sexual and hormonal quality of life as assessed by corresponding Expanded Prostate Cancer Index Composite Short Form (EPIC-26) domains between treatment arms.

III. Compare other measures of quality of life obtained from the European Quality of Life Five Dimension Five Level Scale Questionnaire (EQ5D-5L), European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-30), Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue instruments between the two treatment arms.

IV. Compare time to salvage therapy and time to castration-resistance between treatment arms.

V. Compare local progression (SABR-targeted lesion), biochemical progression, distant metastases, prostate cancer-specific mortality, metastasis-free survival, and overall survival between treatment arms.

VI. Determine adverse events rates and compare rates between the two treatment arms.

EXPLORATORY OBJECTIVE:

I. Evaluate genomic and peripheral tissue and blood markers of treatment response.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive placebo orally (PO) once daily (QD) on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity.

Patients may also undergo bone scan, computed tomography (CT), magnetic resonance imaging (MRI), prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.

After completion of study treatment, patients are followed up at 9 and 12 months, subsequently every 6 months to month 60, and then annually thereafter or at the time of progression.

Study Timeline

• Study First Submitted: 2021-09-13
• Study First Submitted QC: 2021-09-13
• Study First Posted: 2021-09-22
• Study Start: 2022-04-20
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-04
• Last Update Posted: 2025-03-07
• Primary Completion: 2029-02-01
• Study Completion: 2029-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 260

Inclusion Criteria

• Pathologically (histologically or cytologically) proven diagnosis of prostate adenocarcinoma at any anatomical location (for example, prostate, metastatic site), including intraductal or ductal carcinoma, at any time before registration

• Age >= 18 years

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 within 180 days prior to registration

• Prior curative-intent treatment to the prostate, by either:

  • External beam and/or brachytherapy to: Prostate alone, prostate and seminal vesicles, prostate and pelvic nodes, or radiation to all three sites
  • Radical prostatectomy alone, radical prostatectomy plus postoperative radiotherapy to the prostate bed, or radical prostatectomy plus postoperative radiotherapy to the pelvic nodes

• Must meet study entry criteria based on the following diagnostic workup within 120 days prior to registration:

  • History and physical examination;
  • Fluciclovine or PSMA PET scan (must be positive with exception of local disease);
  • PET must be combined with either CT or MRI, but a diagnostic CT or MRI reading/interpretation is not required

• 1 - 5 oligometastatic lesions in bone and/or nodal/soft tissue sites on fluciclovine or PSMA PET within 180 days prior to registration and includes at least ONE of the following:

  • Bone - each metastasis is counted (for example, 2 distinct lesions in the right ilium count as 2 oligometastatic lesions)
  • Extrapelvic Nodal/ soft tissue - requires at least one extrapelvic inguinal or a nodal/soft tissue lesion superior to the iliac bifurcation (that is, American Joint Committee on Cancer [AJCC] M1a version 8)
  • Note: Although a patient must have bone and/or extrapelvic disease to be eligible, when counting the number of oligometastatic lesions, each lymph node lesion, whether pelvic or extrapelvic, is counted (for example, 2 distinct lymph nodes in the right external iliac basin count as 2 oligometastatic lesions; one extrapelvic and one pelvic node count as 2 oligometastic lesions, etc)

• Serum total prostate-specific antigen (PSA) =< 10.0 ng/mL that also meets ONE of the following PSA recurrence definitions:

  • PSA >= post-radiation therapy (RT) nadir PSA + 2 ng/mL, obtained within 180 days prior to registration, if patient received-radiation therapy to intact prostate, or
  • Current PSA >= 0.2 ng/mL, with a second confirmatory PSA >= 0.2 ng/mL if patient received a radical prostatectomy with or without post-op RT. The initial PSA may be outside 180 days BUT the second confirmatory PSA must be within 180 days prior to registration, or
  • PSA > 0.2 ng/mL with at least two rises from treatment nadir with the most recent PSA within 180 days prior to registration, if patient received radiation therapy to intact prostate

• Must have >= 3 PSA values within the last two years since end of primary treatment or within the last 2 years prior to registration, whichever is less

  • Note: PSA doubling time must be calculated by entering all PSA values since end of primary treatment or within the last 2 years prior to registration (whichever is less) into the PSA Doubling Time Calculator found at MDCalc.com

• Serum total testosterone >= 100 ng/dL within 180 days prior to registration

  • Note: Prior androgen deprivation therapy (other than bilateral orchiectomy) is allowed if discontinued prior to registration and serum total testosterone is >= 100 ng/dL

• Total bilirubin: =< 1.5 x institutional upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, subject is eligible if direct bilirubin is =< 1.5 x ULN) (within 180 days prior to registration)

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]): =< 2.5 x institutional ULN (within 180 days prior to registration)

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

  • Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B)

• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

  • Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

• The patient must agree to use a highly effective contraception (even men with vasectomies) if he is having sex with a woman of childbearing potential or with a woman who is pregnant while on study drug and for 2 weeks following the last dose of study drug

• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

Exclusion Criteria

• Clinical, biopsy-proven, or radiologic (conventional or PET imaging) evidence of local tumor recurrence in the prostate and/or periprostatic/seminal vesicle region after radiotherapy, or in the prostate bed after prostatectomy

  • Note: if a patient had a prior local recurrence and received local salvage therapy, the patient is eligible if there is no current evidence of disease in the prostate/prostate bed. Patients with positive findings on examination or imaging remain eligible if biopsy of the site is negative for cancer. Patients who have a positive PET scan in the prostate or prostate bed and have undergone local therapy since PET but prior to enrollment to NRG-GU011 are eligible without a repeat PET scan

• Currently on androgen deprivation or anti-androgen therapy

• Spinal cord compression, or spinal intramedullary, brain, and/or visceral (for example liver, lung, etc.) metastasis

  • Note: Spinal metastases (PET-detected) with epidural extension are eligible if there is > 0.3 cm spatial separation between the gross tumor volume and spinal cord

• Biopsy-proven prostatic carcinoma with signet-ring, sarcomatoid, or neuroendocrine features (for example, small cell)

• Prior metastatic or non-metastatic, invasive malignancy (except non metastatic, non-melanomatous skin cancer) unless continuously disease free for >= 3 years

• Prior chemotherapy for prostate cancer or bilateral orchiectomy

  • Note: Prior chemotherapy for a different cancer is allowed if continuously disease-free for >= 3 years

• Prior radiotherapy to a lesion (i.e. oligometastatic recurrence by PET)

  • Note: Lesions outside of a previously irradiated planning treatment volume (PTV) are eligible as long as the prescription isovolume dose of any prior radiotherapy course is > 2.0 cm distant from new lesion

• Inability to treat all oligometastatic sites with radiotherapy in the judgement of the investigator

• Intrapelvic lymph nodes as only site of prostate cancer recurrence

• Inability to swallow whole, undivided, unchewed, and uncrushed pills

• Known gastrointestinal disorder affecting oral medication absorption

• Co-morbidity defined as follows:

  • Patients with any comorbidities that would prohibit completion of protocol specified therapy
  • Inflammatory bowel disease in patients in whom abdominopelvic radiotherapy is planned
  • History of congenital long QT syndrome
  • Current severe or unstable angina
  • New York Heart Association functional classification III/IV heart failure (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (placebo, SABR)	Biospecimen Collection	Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Arm I (placebo, SABR)	Bone Scan	Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Arm I (placebo, SABR)	Computed Tomography	Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Arm I (placebo, SABR)	Fluciclovine F18	Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Arm I (placebo, SABR)	Magnetic Resonance Imaging	Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Arm I (placebo, SABR)	Placebo Administration	Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Arm I (placebo, SABR)	Positron Emission Tomography	Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Arm I (placebo, SABR)	PSMA PET Scan	Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Arm I (placebo, SABR)	Quality-of-Life Assessment	Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Arm I (placebo, SABR)	Stereotactic Body Radiation Therapy	Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Arm II (relugolix, SABR)	Biospecimen Collection	Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Arm II (relugolix, SABR)	Bone Scan	Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Arm II (relugolix, SABR)	Computed Tomography	Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Arm II (relugolix, SABR)	Fluciclovine F18	Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Arm II (relugolix, SABR)	Magnetic Resonance Imaging	Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Arm II (relugolix, SABR)	Positron Emission Tomography	Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Arm II (relugolix, SABR)	PSMA PET Scan	Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Arm II (relugolix, SABR)	Quality-of-Life Assessment	Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Arm II (relugolix, SABR)	Relugolix	Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.
Arm II (relugolix, SABR)	Stereotactic Body Radiation Therapy	Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, CT, MRI, PSMA PET/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial.

Primary Outcome Measures

Name	Time	Method
Radiological progression-free survival (rPFS)	Time from randomization to the occurrence of radiological progression detected by conventional imaging or death from any cause, assessed up to 5 years	The rPFS curves will be estimated by the Kaplan-Meier method and compared between the two treatment arms using a one-sided, logrank test stratified by the three randomization factors.

Secondary Outcome Measures

Name	Time	Method
Positron emission tomography (PET)-based radiological progression-free survival	Time from randomization to the occurrence of conventional or PET-based radiological progression or death from any cause, assessed up to 5 years	Will be estimated by the Kaplan-Meier method and compared between treatments arms by stratified logrank test. Cox regression models will also be fit, adjusted for the stratification factors and other prognostic baseline factors, to estimate hazard ratios, together with 95% confidence intervals.
Metastasis-free survival	From randomization to distant metastases or death from any cause, assessed up to 5 years	Will be estimated by the Kaplan-Meier method and compared between treatments arms by stratified logrank test. Cox regression models will also be fit, adjusted for the stratification factors and other prognostic baseline factors, to estimate hazard ratios, together with 95% confidence intervals.
Overall survival	From randomization to death from any cause, assessed up to 5 years	Will be estimated by the Kaplan-Meier method and compared between treatments arms by stratified logrank test. Cox regression models will also be fit, adjusted for the stratification factors and other prognostic baseline factors, to estimate hazard ratios, together with 95% confidence intervals.
Sexual and hormonal quality of life	Up to 5 years from randomization	Assessed by Expanded Prostate Cancer Index Composite Short Form (EPIC-26).
Quality of life	Up to 5 years from randomization	Assessed by European Quality of Life Five Dimension Five Level Scale Questionnaire (EQ5D-5L) and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-30).
Fatigue	Up to 5 years from randomization	Assessed by Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue short form.
Time from randomization to administration of salvage therapy	Up to 5 years from randomization	Will be analyzed using competing-risk methods where, in each case, death prior to occurrence of the event in question will be considered a competing risk. (In the case of death from prostate cancer, the competing risk will be non-prostate cancer death.) Cumulative incidence curves will be generated and compared using the Fine-Gray method and sub-distribution hazard ratios (SHRs) will be estimated, along with 95% confidence intervals, to summarize the magnitude of the treatment effect. In addition to Fine-Gray tests, we will estimate cause-specific hazard ratios by treating the competing risk as a censored observation via stratified logrank tests and Cox regression modelling.
Time from randomization to castrate-resistant prostate cancer	Up to 5 years from randomization	Will be analyzed using competing-risk methods where, in each case, death prior to occurrence of the event in question will be considered a competing risk. (In the case of death from prostate cancer, the competing risk will be non-prostate cancer death.) Cumulative incidence curves will be generated and compared using the Fine-Gray method and SHRs will be estimated, along with 95% confidence intervals, to summarize the magnitude of the treatment effect. In addition to Fine-Gray tests, we will estimate cause-specific hazard ratios by treating the competing risk as a censored observation via stratified logrank tests and Cox regression modelling.
Time from randomization to local progression within a stereotactic ablative body radiation therapy (SABR)-targeted lesion	Up to 5 years from randomization	Will be analyzed using competing-risk methods where, in each case, death prior to occurrence of the event in question will be considered a competing risk. (In the case of death from prostate cancer, the competing risk will be non-prostate cancer death.) Cumulative incidence curves will be generated and compared using the Fine-Gray method and SHRs will be estimated, along with 95% confidence intervals, to summarize the magnitude of the treatment effect. In addition to Fine-Gray tests, we will estimate cause-specific hazard ratios by treating the competing risk as a censored observation via stratified logrank tests and Cox regression modelling.
Time from randomization to biochemical progression	Up to 5 years from randomization	Will be analyzed using competing-risk methods where, in each case, death prior to occurrence of the event in question will be considered a competing risk. (In the case of death from prostate cancer, the competing risk will be non-prostate cancer death.) Cumulative incidence curves will be generated and compared using the Fine-Gray method and SHRs will be estimated, along with 95% confidence intervals, to summarize the magnitude of the treatment effect. In addition to Fine-Gray tests, we will estimate cause-specific hazard ratios by treating the competing risk as a censored observation via stratified logrank tests and Cox regression modelling.
Time from randomization to the occurrence of distance metastases	Up to 5 years from randomization	Will be analyzed using competing-risk methods where, in each case, death prior to occurrence of the event in question will be considered a competing risk. (In the case of death from prostate cancer, the competing risk will be non-prostate cancer death.) Cumulative incidence curves will be generated and compared using the Fine-Gray method and SHRs will be estimated, along with 95% confidence intervals, to summarize the magnitude of the treatment effect. In addition to Fine-Gray tests, we will estimate cause-specific hazard ratios by treating the competing risk as a censored observation via stratified logrank tests and Cox regression modelling.
Time from randomization to death from prostate cancer	Up to 5 years from randomization	Will be analyzed using competing-risk methods where, in each case, death prior to occurrence of the event in question will be considered a competing risk. (In the case of death from prostate cancer, the competing risk will be non-prostate cancer death.) Cumulative incidence curves will be generated and compared using the Fine-Gray method and SHRs will be estimated, along with 95% confidence intervals, to summarize the magnitude of the treatment effect. In addition to Fine-Gray tests, we will estimate cause-specific hazard ratios by treating the competing risk as a censored observation via stratified logrank tests and Cox regression modelling.

Trial Locations

Locations (213)

Cancer Center at Saint Joseph's; 🇺🇸 Phoenix, Arizona, United States

Alta Bates Summit Medical Center-Herrick Campus; 🇺🇸 Berkeley, California, United States

Tower Cancer Research Foundation; 🇺🇸 Beverly Hills, California, United States

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care; 🇺🇸 Irvine, California, United States

Los Angeles General Medical Center; 🇺🇸 Los Angeles, California, United States

USC / Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Memorial Medical Center; 🇺🇸 Modesto, California, United States

UC Irvine Health/Chao Family Comprehensive Cancer Center; 🇺🇸 Orange, California, United States

Sutter Pacific Medical Foundation; 🇺🇸 Santa Rosa, California, United States

Sutter Solano Medical Center/Cancer Center; 🇺🇸 Vallejo, California, United States

UCHealth University of Colorado Hospital; 🇺🇸 Aurora, Colorado, United States

Rocky Mountain Cancer Centers-Boulder; 🇺🇸 Boulder, Colorado, United States

UCHealth Memorial Hospital Central; 🇺🇸 Colorado Springs, Colorado, United States

Memorial Hospital North; 🇺🇸 Colorado Springs, Colorado, United States

Shaw Cancer Center; 🇺🇸 Edwards, Colorado, United States

Poudre Valley Hospital; 🇺🇸 Fort Collins, Colorado, United States

Cancer Care and Hematology-Fort Collins; 🇺🇸 Fort Collins, Colorado, United States

Banner North Colorado Medical Center; 🇺🇸 Greeley, Colorado, United States

UCHealth Greeley Hospital; 🇺🇸 Greeley, Colorado, United States

UCHealth Highlands Ranch Hospital; 🇺🇸 Highlands Ranch, Colorado, United States

Medical Center of the Rockies; 🇺🇸 Loveland, Colorado, United States

Banner McKee Medical Center; 🇺🇸 Loveland, Colorado, United States

Beebe South Coastal Health Campus; 🇺🇸 Millville, Delaware, United States

Helen F Graham Cancer Center; 🇺🇸 Newark, Delaware, United States

Medical Oncology Hematology Consultants PA; 🇺🇸 Newark, Delaware, United States

Beebe Health Campus; 🇺🇸 Rehoboth Beach, Delaware, United States

George Washington University Medical Center; 🇺🇸 Washington, District of Columbia, United States

Jupiter Medical Center; 🇺🇸 Jupiter, Florida, United States

GenesisCare USA - Lakewood Ranch; 🇺🇸 Lakewood Ranch, Florida, United States

AdventHealth Orlando; 🇺🇸 Orlando, Florida, United States

GenesisCare USA - Plantation; 🇺🇸 Plantation, Florida, United States

Moffitt Cancer Center-International Plaza; 🇺🇸 Tampa, Florida, United States

Moffitt Cancer Center - McKinley Campus; 🇺🇸 Tampa, Florida, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Grady Health System; 🇺🇸 Atlanta, Georgia, United States

Emory University Hospital Midtown; 🇺🇸 Atlanta, Georgia, United States

Piedmont Hospital; 🇺🇸 Atlanta, Georgia, United States

Emory University Hospital/Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

Emory Saint Joseph's Hospital; 🇺🇸 Atlanta, Georgia, United States

Piedmont Fayette Hospital; 🇺🇸 Fayetteville, Georgia, United States

Emory Johns Creek Hospital; 🇺🇸 Johns Creek, Georgia, United States

Advocate Good Shepherd Hospital; 🇺🇸 Barrington, Illinois, United States

Advocate Illinois Masonic Medical Center; 🇺🇸 Chicago, Illinois, United States

AMG Crystal Lake - Oncology; 🇺🇸 Crystal Lake, Illinois, United States

Carle at The Riverfront; 🇺🇸 Danville, Illinois, United States

Decatur Memorial Hospital; 🇺🇸 Decatur, Illinois, United States

Advocate Good Samaritan Hospital; 🇺🇸 Downers Grove, Illinois, United States

Crossroads Cancer Center; 🇺🇸 Effingham, Illinois, United States

Advocate Sherman Hospital; 🇺🇸 Elgin, Illinois, United States

Advocate South Suburban Hospital; 🇺🇸 Hazel Crest, Illinois, United States

AMG Libertyville - Oncology; 🇺🇸 Libertyville, Illinois, United States

Carle Physician Group-Mattoon/Charleston; 🇺🇸 Mattoon, Illinois, United States

HSHS Saint Elizabeth's Hospital; 🇺🇸 O'Fallon, Illinois, United States

Advocate Christ Medical Center; 🇺🇸 Oak Lawn, Illinois, United States

Advocate Lutheran General Hospital; 🇺🇸 Park Ridge, Illinois, United States

Methodist Medical Center of Illinois; 🇺🇸 Peoria, Illinois, United States

OSF Saint Francis Medical Center; 🇺🇸 Peoria, Illinois, United States

Memorial Hospital East; 🇺🇸 Shiloh, Illinois, United States

Springfield Memorial Hospital; 🇺🇸 Springfield, Illinois, United States

Carle Cancer Center; 🇺🇸 Urbana, Illinois, United States

Parkview Regional Medical Center; 🇺🇸 Fort Wayne, Indiana, United States

Goshen Center for Cancer Care; 🇺🇸 Goshen, Indiana, United States

Mary Greeley Medical Center; 🇺🇸 Ames, Iowa, United States

McFarland Clinic - Ames; 🇺🇸 Ames, Iowa, United States

Iowa Methodist Medical Center; 🇺🇸 Des Moines, Iowa, United States

Mission Cancer and Blood - Des Moines; 🇺🇸 Des Moines, Iowa, United States

The James Graham Brown Cancer Center at University of Louisville; 🇺🇸 Louisville, Kentucky, United States

UofL Health Medical Center Northeast; 🇺🇸 Louisville, Kentucky, United States

Mary Bird Perkins Cancer Center; 🇺🇸 Baton Rouge, Louisiana, United States

Mary Bird Perkins Cancer Center - Metairie; 🇺🇸 Metairie, Louisiana, United States

East Jefferson General Hospital; 🇺🇸 Metairie, Louisiana, United States

LSU Healthcare Network / Metairie Multi-Specialty Clinic; 🇺🇸 Metairie, Louisiana, United States

University Medical Center New Orleans; 🇺🇸 New Orleans, Louisiana, United States

Trinity Health Saint Joseph Mercy Hospital Ann Arbor; 🇺🇸 Ann Arbor, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Brighton; 🇺🇸 Brighton, Michigan, United States

Trinity Health Medical Center - Brighton; 🇺🇸 Brighton, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Canton; 🇺🇸 Canton, Michigan, United States

Trinity Health Medical Center - Canton; 🇺🇸 Canton, Michigan, United States

Chelsea Hospital; 🇺🇸 Chelsea, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital; 🇺🇸 Chelsea, Michigan, United States

Michigan Healthcare Professionals Clarkston; 🇺🇸 Clarkston, Michigan, United States

Michigan Healthcare Professionals Farmington; 🇺🇸 Farmington Hills, Michigan, United States

Corewell Health Grand Rapids Hospitals - Butterworth Hospital; 🇺🇸 Grand Rapids, Michigan, United States

Trinity Health Grand Rapids Hospital; 🇺🇸 Grand Rapids, Michigan, United States

Bronson Methodist Hospital; 🇺🇸 Kalamazoo, Michigan, United States

University of Michigan Health - Sparrow Lansing; 🇺🇸 Lansing, Michigan, United States

Trinity Health Saint Mary Mercy Livonia Hospital; 🇺🇸 Livonia, Michigan, United States

Michigan Healthcare Professionals Macomb; 🇺🇸 Macomb, Michigan, United States

Michigan Healthcare Professionals Madison Heights; 🇺🇸 Madison Heights, Michigan, United States

Trinity Health Saint Joseph Mercy Oakland Hospital; 🇺🇸 Pontiac, Michigan, United States

Corewell Health William Beaumont University Hospital; 🇺🇸 Royal Oak, Michigan, United States

Munson Medical Center; 🇺🇸 Traverse City, Michigan, United States

Corewell Health Beaumont Troy Hospital; 🇺🇸 Troy, Michigan, United States

Michigan Healthcare Professionals Troy; 🇺🇸 Troy, Michigan, United States

University of Michigan Health - West; 🇺🇸 Wyoming, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus; 🇺🇸 Ypsilanti, Michigan, United States

Regions Hospital; 🇺🇸 Saint Paul, Minnesota, United States

Saint Francis Medical Center; 🇺🇸 Cape Girardeau, Missouri, United States

Siteman Cancer Center at West County Hospital; 🇺🇸 Creve Coeur, Missouri, United States

Delbert Day Cancer Institute at PCRMC; 🇺🇸 Rolla, Missouri, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Siteman Cancer Center-South County; 🇺🇸 Saint Louis, Missouri, United States

Siteman Cancer Center at Christian Hospital; 🇺🇸 Saint Louis, Missouri, United States

Siteman Cancer Center at Saint Peters Hospital; 🇺🇸 Saint Peters, Missouri, United States

Benefis Sletten Cancer Institute; 🇺🇸 Great Falls, Montana, United States

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center; 🇺🇸 Lebanon, New Hampshire, United States

The Valley Hospital - Luckow Pavilion; 🇺🇸 Paramus, New Jersey, United States

University of New Mexico Cancer Center; 🇺🇸 Albuquerque, New Mexico, United States

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States

Highland Hospital; 🇺🇸 Rochester, New York, United States

University of Rochester; 🇺🇸 Rochester, New York, United States

Wilmot Cancer Institute at Webster; 🇺🇸 Webster, New York, United States

East Carolina University; 🇺🇸 Greenville, North Carolina, United States

Sanford Broadway Medical Center; 🇺🇸 Fargo, North Dakota, United States

Sanford Roger Maris Cancer Center; 🇺🇸 Fargo, North Dakota, United States

UH Seidman Cancer Center at UH Avon Health Center; 🇺🇸 Avon, Ohio, United States

UHHS-Chagrin Highlands Medical Center; 🇺🇸 Beachwood, Ohio, United States

Miami Valley Hospital South; 🇺🇸 Centerville, Ohio, United States

Case Western Reserve University; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Miami Valley Hospital; 🇺🇸 Dayton, Ohio, United States

Premier Blood and Cancer Center; 🇺🇸 Dayton, Ohio, United States

Miami Valley Hospital North; 🇺🇸 Dayton, Ohio, United States

Atrium Medical Center-Middletown Regional Hospital; 🇺🇸 Franklin, Ohio, United States

UH Seidman Cancer Center at Lake Health Mentor Campus; 🇺🇸 Mentor, Ohio, United States

University Hospitals Parma Medical Center; 🇺🇸 Parma, Ohio, United States

University Hospitals Portage Medical Center; 🇺🇸 Ravenna, Ohio, United States

ProMedica Flower Hospital; 🇺🇸 Sylvania, Ohio, United States

Upper Valley Medical Center; 🇺🇸 Troy, Ohio, United States

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

UPMC Altoona; 🇺🇸 Altoona, Pennsylvania, United States

UPMC-Heritage Valley Health System Beaver; 🇺🇸 Beaver, Pennsylvania, United States

Bryn Mawr Hospital; 🇺🇸 Bryn Mawr, Pennsylvania, United States

Carlisle Regional Cancer Center; 🇺🇸 Carlisle, Pennsylvania, United States

Christiana Care Health System-Concord Health Center; 🇺🇸 Chadds Ford, Pennsylvania, United States

Chambersburg Hospital; 🇺🇸 Chambersburg, Pennsylvania, United States

Geisinger Medical Center; 🇺🇸 Danville, Pennsylvania, United States

Fox Chase Cancer Center - East Norriton Hospital Outpatient Center; 🇺🇸 East Norriton, Pennsylvania, United States

Ephrata Cancer Center; 🇺🇸 Ephrata, Pennsylvania, United States

UPMC Hillman Cancer Center Erie; 🇺🇸 Erie, Pennsylvania, United States

UPMC Cancer Center at UPMC Horizon; 🇺🇸 Farrell, Pennsylvania, United States

Fox Chase Cancer Center Buckingham; 🇺🇸 Furlong, Pennsylvania, United States

Adams Cancer Center; 🇺🇸 Gettysburg, Pennsylvania, United States

UPMC Pinnacle Cancer Center/Community Osteopathic Campus; 🇺🇸 Harrisburg, Pennsylvania, United States

Penn State Milton S Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States

IRMC Cancer Center; 🇺🇸 Indiana, Pennsylvania, United States

Sechler Family Cancer Center; 🇺🇸 Lebanon, Pennsylvania, United States

Geisinger Medical Oncology-Lewisburg; 🇺🇸 Lewisburg, Pennsylvania, United States

UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion; 🇺🇸 Mechanicsburg, Pennsylvania, United States

Riddle Memorial Hospital; 🇺🇸 Media, Pennsylvania, United States

UPMC Hillman Cancer Center in Coraopolis; 🇺🇸 Moon, Pennsylvania, United States

Paoli Memorial Hospital; 🇺🇸 Paoli, Pennsylvania, United States

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

UPMC-Magee Womens Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC-Saint Margaret; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Pittsburgh Cancer Institute (UPCI); 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC-Shadyside Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC-Passavant Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

Geisinger Cancer Services-Pottsville; 🇺🇸 Pottsville, Pennsylvania, United States

UPMC Cancer Center at UPMC Northwest; 🇺🇸 Seneca, Pennsylvania, United States

UPMC Washington Hospital Radiation Oncology; 🇺🇸 Washington, Pennsylvania, United States

Geisinger Wyoming Valley/Henry Cancer Center; 🇺🇸 Wilkes-Barre, Pennsylvania, United States

Divine Providence Hospital; 🇺🇸 Williamsport, Pennsylvania, United States

Lankenau Medical Center; 🇺🇸 Wynnewood, Pennsylvania, United States

WellSpan Health-York Cancer Center; 🇺🇸 York, Pennsylvania, United States

UPMC Memorial; 🇺🇸 York, Pennsylvania, United States

Carolina Regional Cancer Center; 🇺🇸 Myrtle Beach, South Carolina, United States

Sanford Cancer Center Oncology Clinic; 🇺🇸 Sioux Falls, South Dakota, United States

Sanford USD Medical Center - Sioux Falls; 🇺🇸 Sioux Falls, South Dakota, United States

Covenant Medical Center-Lakeside; 🇺🇸 Lubbock, Texas, United States

Dartmouth Cancer Center - North; 🇺🇸 Saint Johnsbury, Vermont, United States

VCU Massey Cancer Center at Stony Point; 🇺🇸 Richmond, Virginia, United States

Virginia Commonwealth University/Massey Cancer Center; 🇺🇸 Richmond, Virginia, United States

VCU Community Memorial Health Center; 🇺🇸 South Hill, Virginia, United States

FHCC at EvergreenHealth; 🇺🇸 Kirkland, Washington, United States

Fred Hutchinson Cancer Center; 🇺🇸 Seattle, Washington, United States

FHCC at Northwest Hospital; 🇺🇸 Seattle, Washington, United States

University of Washington Medical Center - Montlake; 🇺🇸 Seattle, Washington, United States

Edwards Comprehensive Cancer Center; 🇺🇸 Huntington, West Virginia, United States

Langlade Hospital and Cancer Center; 🇺🇸 Antigo, Wisconsin, United States

Marshfield Medical Center-EC Cancer Center; 🇺🇸 Eau Claire, Wisconsin, United States

Aurora Cancer Care-Grafton; 🇺🇸 Grafton, Wisconsin, United States

Aurora BayCare Medical Center; 🇺🇸 Green Bay, Wisconsin, United States

Aurora Bay Area Medical Group-Marinette; 🇺🇸 Marinette, Wisconsin, United States

Marshfield Medical Center-Marshfield; 🇺🇸 Marshfield, Wisconsin, United States

Froedtert Menomonee Falls Hospital; 🇺🇸 Menomonee Falls, Wisconsin, United States

Aurora Saint Luke's Medical Center; 🇺🇸 Milwaukee, Wisconsin, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Aurora Sinai Medical Center; 🇺🇸 Milwaukee, Wisconsin, United States

Marshfield Medical Center - Minocqua; 🇺🇸 Minocqua, Wisconsin, United States

ProHealth D N Greenwald Center; 🇺🇸 Mukwonago, Wisconsin, United States

Cancer Center of Western Wisconsin; 🇺🇸 New Richmond, Wisconsin, United States

Drexel Town Square Health Center; 🇺🇸 Oak Creek, Wisconsin, United States

ProHealth Oconomowoc Memorial Hospital; 🇺🇸 Oconomowoc, Wisconsin, United States

Vince Lombardi Cancer Clinic - Oshkosh; 🇺🇸 Oshkosh, Wisconsin, United States

Aspirus Cancer Care - James Beck Cancer Center; 🇺🇸 Rhinelander, Wisconsin, United States

Marshfield Medical Center-Rice Lake; 🇺🇸 Rice Lake, Wisconsin, United States

Vince Lombardi Cancer Clinic-Sheboygan; 🇺🇸 Sheboygan, Wisconsin, United States

Aspirus Cancer Care - Stevens Point; 🇺🇸 Stevens Point, Wisconsin, United States

Marshfield Medical Center-River Region at Stevens Point; 🇺🇸 Stevens Point, Wisconsin, United States

Aurora Medical Center in Summit; 🇺🇸 Summit, Wisconsin, United States

UW Cancer Center at ProHealth Care; 🇺🇸 Waukesha, Wisconsin, United States

Aspirus Regional Cancer Center; 🇺🇸 Wausau, Wisconsin, United States

Aurora Cancer Care-Milwaukee West; 🇺🇸 Wauwatosa, Wisconsin, United States

Aurora West Allis Medical Center; 🇺🇸 West Allis, Wisconsin, United States

Froedtert West Bend Hospital/Kraemer Cancer Center; 🇺🇸 West Bend, Wisconsin, United States

Marshfield Medical Center - Weston; 🇺🇸 Weston, Wisconsin, United States

Aspirus Cancer Care - Wisconsin Rapids; 🇺🇸 Wisconsin Rapids, Wisconsin, United States

University Health Network-Princess Margaret Hospital; 🇨🇦 Toronto, Ontario, Canada

CHUM - Centre Hospitalier de l'Universite de Montreal; 🇨🇦 Montreal, Quebec, Canada

CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ); 🇨🇦 Quebec City, Quebec, Canada