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Active, not recruitingNCT03371719Updated Oct 1, 2026Results posted

Radiation Therapy With or Without Apalutamide in Treating Patients With Recurrent Prostate Cancer, the BALANCE Trial

A Phase 2 interventional study of Apalutamide and External Beam Radiation Therapy in Recurrent Prostate Carcinoma, Stage III Prostate Adenocarcinoma AJCC v7 and Stage IV Prostate Adenocarcinoma AJCC v7, sponsored by NRG Oncology. Active, not recruiting at 360 sites in 2 countries. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-01.

Sponsored by NRG Oncology · Phase 2, Interventional, and Treatment

Updated Oct 1, 2026Posted results revisedStudy completion moved+2 moreGo to Updates ↓
Phase
Phase 2
Study type
Interventional
Enrollment
298
Allocation
Randomized
Ages
18 Years and older
Sex
Male
01

Study summary

This phase II trial studies how well radiation therapy with or without apalutamide works in treating patients with prostate cancer that has come back (recurrent). Radiation therapy uses high energy x-ray to kill tumor cells and shrink tumors. Androgen can cause the growth of prostate cancer cells. Drugs, such as apalutamide, may lessen the amount of androgen made by the body. Giving radiation therapy and apalutamide may work better at treating prostate cancer compared to radiation therapy alone.

Read the detailed description

PRIMARY OBJECTIVE:

I. To determine whether, in men with post-prostatectomy prostate-specific antigen (PSA) recurrences, salvage radiation (SRT) with enhanced anti-androgen therapy with apalutamide will improve biochemical progression-free survival (bPFS) compared to SRT alone.

SECONDARY OBJECTIVES:

I. To assess whether molecular stratification by the PAM50 gene expression clustering will identify subsets of prostate cancer (luminal A or basal, luminal B) which derive the greatest benefit from anti-androgen therapy.

II. To assess overall survival. III. To assess cancer-specific mortality. IV. To assess metastasis-free survival. V. To assess distant metastasis. VI. To assess local-regional progression. VII. To assess PSA nadir during first year of treatment and prior to initiation of any hormonal salvage therapy.

VIII. To assess initiation of salvage hormonal therapy. IX. To assess PSA with a non-castrate testosterone at 1 and 3 years post randomization: PSA \< 0.1 ng/ml and testosterone >= 50 ng/dl.

X. To assess acute and late physician-reported morbidity (per the Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) after SRT +/- apalutamide.

XI. To assess acute and late patient-reported symptomatic adverse events morbidity (per the patient reported outcomes [PRO]-CTCAE) after SRT +/- apalutamide.

XII. To assess testosterone levels at 3, 6, 9, 12, and 36 months post randomization.

EXPLORATORY OBJECTIVE:

I. To assess the prognostic and predictive value of the genomic classifier Decipher.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: Patients undergo external beam radiation therapy on day 1 for 7-8 weeks. Beginning on day of radiation therapy, patients receive placebo orally (PO) once daily (QD) on days 1-30. Treatment repeats every 30 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

ARM 2: Patients undergo external beam radiation therapy on day 1 for 7-8 weeks. Beginning on day of radiation therapy, patients receive apalutamide PO QD on days 1-30. Treatment repeats every 30 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years, and then yearly thereafter.

02

Conditions studied

  • Recurrent Prostate Carcinoma
  • Stage III Prostate Adenocarcinoma AJCC v7
  • Stage IV Prostate Adenocarcinoma AJCC v7

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03

In context

Prostatic Neoplasms

7,046 studies on the registry are indexed under Prostatic Neoplasms; 1,580 are open to participants now.

This study's enrollment of 298 is above the median of 60 across 5,348 interventional studies indexed under Prostatic Neoplasms.

Browse Prostatic Neoplasms studies →

Lead sponsor

NRG Oncology is the lead sponsor of 72 studies on the registry; 25 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Male
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Pathologically (histologically) proven diagnosis of prostate adenocarcinoma; prostatectomy must have been performed within 10 years prior to Step 1 registration and any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted

  • Post-prostatectomy patients with a detectable serum PSA (>= 0.1, but =\< 1.0 ng/mL) at study entry (within 90 days of Step 1 registration) and at least one of the following:

    • Gleason score 7-10 (International Society of Urological Pathology [ISUP] grade group 2 to 5)

    • ISUP grade group:

      • Grade group 1 = Gleason score =\< 6,
      • Grade group 2 = Gleason score 3 + 4 = 7,
      • Grade group 3 = Gleason score 4 + 3 = 7,
      • Grade group 4 = Gleason score 8,
      • Grade group 5 = Gleason scores 9 and 10
    • >= T3a disease
    • Persistent elevation of PSA after prostatectomy measured within 90 days after surgery (PSA never became undetectable) of > 0.04 but \< 0.2 ng/mL (PSA nadir)
  • pN0 or pNx
  • History/physical examination within 90 days prior to Step 1 registration
  • performance status of 70-100 within 90 days prior to Step 1 registration
  • Surgical formalin-fixed paraffin-embedded (FFPE) specimen must be available for submission to GenomeDx for genomic analysis on Decipher GRID platform; Note: if Decipher results have already been obtained, in lieu of tissue, results must be submitted to GenomeDx for validation and for GenomeDx to provide the subtyping needed for stratification

  • Prior androgen deprivation therapy (luteinizing hormone-releasing hormone [LHRH] agonist and/or non-steroidal anti-androgen) is allowed if discontinued at least 90 days prior to Step 1 registration and given for =\< 90 days duration

    • For example: patients on prior LHRH analogs (post-prostatectomy), the discontinuation date should be calculated based on the expected duration of the sustained release injection, not simply the injection date of the drug; for instance, if a 22.5 mg sustained release dose of leuprolide acetate is given (3 month duration), then the expected duration of such a dose would be 90 days after the injection date; for a 7.5 mg leuprolide (1 month duration), the discontinuation date would be 30 days after the injection date
    • Please note: finasteride or dutasteride must be stopped before treatment starts but prior usage will not affect eligibility
  • >= 9.0 g/dL, independent of transfusion and/or growth factors within 90 days prior to Step 1 registration
  • count >= 100,000 x 10\^9/uL independent of transfusion and/or growth factors within 90 days prior to Step 1 registration
  • Serum albumin >= 3.0 g/dL within 90 days prior to Step 1 registration
  • (GFR) >= 35 mL/min estimated by or measured directly by 24 hour urine creatinine within 90 days prior to Step 1 registration
  • Serum total =\< 1.5 x (ULN) (Note: in subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =\< 1.5 x ULN, subject is eligible) within 90 days prior to Step 1 registration
  • (AST) or alanine aminotransferase (ALT) \< 2.5 x ULN within 90 days prior to Step 1 registration
  • Testosterone > 50 ng/dL within 90 days prior to Step 1 registration
  • Concomitant medications known to lower the seizure threshold discontinued or substituted at least 4 weeks (30 days) prior to Step 1 registration
  • The patient must agree to use a condom (even men with vasectomies) and another effective method of if he is having sex with a woman of or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug
  • The patient must agree not to donate sperm during the study treatment and for 3 months after receiving the last dose of study drug
  • The patient or a legally authorized representative must provide study-specific prior to study entry

Exclusion criteria

Exclusion Criteria:

  • PRIOR TO STEP 1 REGISTRATION:
  • Definitive clinical, radiologic, or pathologic evidence of disease (M1) or lymph node involvement (N1)
  • Prior invasive (except non-melanomatous skin cancer, carcinoma in situ of the male breast, penis, oral cavity, or stage Ta of the bladder, or stage I completely resected melanoma) unless disease free for a minimum of 2 years
  • Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields

  • History of any of the following:

    • Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year prior to Step 1 registration)
    • History of documented inflammatory bowel disease
    • Transmural myocardial infarction within the last 4 months prior to Step 1 registration
    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to Step 1 registration
    • History of any condition that in the opinion of the investigator, would preclude participation in this study

  • Current evidence of any of the following:

    • Known gastrointestinal disorder affecting absorption of oral medications
    • Active uncontrolled infection (e.g., [HIV] or viral hepatitis)
    • Uncontrolled hypertension
    • Any current condition that in the opinion of the investigator, would preclude participation in this study
  • Prior whole gland ablative therapy (i.e. cryoablation or high intensity focused ultrasound [HIFU]) for prostate cancer is not allowed
  • HIV positive with \< 200 cells/microliter within 30 days prior to registration
  • HIV patients under treatment with highly active antiretroviral therapy (HAART) within 30 days prior to registration regardless of CD4 count; (Note: HIV testing is not required for eligibility for this protocol as it is self-reported; this exclusion criterion is necessary because the treatments involved in this protocol may be and/or interact with HAART)
  • Patients must not plan to participate in any other clinical trials while receiving treatment on this study or being followed post-protocol therapy
  • PRIOR TO STEP 2 REGISTRATION:
  • For patients who have not undergone prior Decipher analysis, submission of the specimen to GenomeDx should be as soon as possible after study registration (Step 1) as these results can take up 21 days after the specimen is received at GenomeDx; Step 2 registration must occur within 6 weeks (42 days) of Step 1 registration; if Decipher results have already been obtained, in lieu of tissue, results must be submitted to GenomeDx for validation
Terms in these criteria, in plain language(16)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Karnofsky performance status (KPS)

A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.

Studies often ask for 60 or 70 and above. Your doctor gives the score.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

CD4 count

The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
298 participants (actual)

Study arms

  • Active comparator
    Arm 1 (radiation therapy, placebo)

    Patients undergo external beam radiation therapy on day 1 for 7-8 weeks. Beginning on day of radiation therapy, patients receive placebo PO QD on days 1-30. Treatment repeats every 30 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

    Radiation: External Beam Radiation Therapy · Other: Placebo Administration

  • Experimental
    Arm 2 (radiation therapy, apalutamide)

    Patients undergo external beam radiation therapy on day 1 for 7-8 weeks. Beginning on day of radiation therapy, patients receive apalutamide PO QD on days 1-30. Treatment repeats every 30 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

    Drug: Apalutamide · Radiation: External Beam Radiation Therapy

Interventions

  • DrugApalutamide

    Given PO

    Also known as: ARN 509, ARN-509, ARN509, Erleada, JNJ 56021927, JNJ-56021927

  • RadiationExternal Beam Radiation Therapy

    Undergo external beam radiation therapy

    Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy, External Beam Radiotherapy (conventional), External Beam RT, external radiation, External Radiation Therapy, external-beam radiation, Radiation, External Beam, Teleradiotherapy, Teletherapy, Teletherapy Radiation

  • OtherPlacebo Administration

    Given PO

06

What researchers measure

Primary outcomes

  1. Percentage of Participants Alive Without Biochemical Progression (Biochemical Progression-free Survival)

    Biochemical progression is defined as the first occurrence of the following: * A rise in PSA ≥0.2 ng/mL from nadir PSA, confirmed by a second PSA measurement equal to or higher than the first; * Clinical or radiographic local, regional, or distant metastases * Death from any cause. Biochemical progression-free survival rates are estimated using the Kaplan-Meier method, censoring participants alive at time of analysis. Arms are compared within molecular subtype group sequentially based on a study design that determines if and how to incorporate the biomarker in a in a subsequent phase III trial.

    Time frame: From randomization to biochemical progression or last follow-up if alive. Median follow-up at time of analysis among surviving patients was 5.0 years. Five-year rates are presented.

Secondary outcomes

  1. Percentage of Participants Alive (Overall Survival)

    Survival rates are estimated using the Kaplan-Meier method, censoring participants alive at time of analysis.

    Time frame: From randomization to death or last follow-up if alive. Median follow-up at time of analysis among surviving patients was 5.0 years. Five-year rates are presented.

  2. Percentage of Participants Who Have Died Due to Prostate Cancer (Cancer-specific Mortality (CSM))

    Prostate cancer death rates were estimated using the cumulative incidence method in which death from other causes is treated as a competing risk and alive patients are censored.

    Time frame: From the date of randomization to the date of death due to prostate cancer or last follow-up if alive. Median follow-up at time of analysis among surviving patients was 5.0 years. Five-year rates are presented.

  3. Percentage of Participants Alive Without Distant Metastases (Metastasis-free Survival (MFS))

    Distant metastases are defined as clinical or radiographic appearance of disseminated disease. MFS rates are estimated using the Kaplan-Meier method, censoring participants alive without metastases at time of analysis.

    Time frame: From randomization to date of first distant metastasis or death, or last follow-up if alive. Median follow-up at time of analysis among surviving patients was 5.0 years. Five-year rates are presented.

  4. Percentage of Participants With Distant Metastasis

    Distant metastases are defined as clinical or radiographic appearance of disseminated disease. Distant metastasis rates are estimated using the cumulative incidence method in which death is treated as competing risk and participants alive without distant metastases are censored at last known follow-up.

    Time frame: From randomization to date of first distant metastasis or death, or last follow-up if alive at time of analysis. Median follow-up at time of analysis was 5.0 years. Five-year rates are presented.

  5. Percentage of Participants Wtih Local-regional Progression

    Local-regional progression is defined as recurrence within the pelvis including lymph nodes below the iliac bifurcation. Local-regional progression rates are estimated using the cumulative incidence method in which death is treated as competing risk and participants alive without local-regional progression are censored at last known follow-up.

    Time frame: From randomization to date of first local or regional recurrence or death, or last follow-up if alive at time of analysis. Median follow-up at time of analysis was 5.0 years. Five-year rates are presented.

  6. PSA Nadir During First Year of Treatment and Prior to Initiation of Any Hormonal Salvage Therapy

    Will be compared between the two groups using a two-sample t-test.

    Time frame: First year of treatment

  7. Percentage of Participants That Started Salvage Hormonal Therapy

    Initiation of salvage hormone therapy (LHRH analogues or non-study anti-androgens) that occurs after completion of SRT. Salvage hormonal therapy rates are estimated using the cumulative incidence method in which death is treated as competing risk and participants alive who have not started salvage hormonal therapy are censored at last known follow-up.

    Time frame: From randomization to initiation of salvage hormonal therapy or death, whichever occurs first, or last follow-up if alive at time of analysis. Median follow-up at time of analysis among surviving patients was 5.0 years. Five-year rates are presented.

  8. Proportion of Participants With Undetectable PSA (< 0.1) and Non-castrate Testosterone (≥ 50 ng/dl) at One and Three Years

    Time frame: One and three years

  9. Number of Participants With Grade 3+ Adverse Events Occurring Within 30 Days After the Completion of RT

    National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.

    Time frame: Up to 30 days after radiation therapy, which lasts approximately 7-8 weeks from treatment start.

  10. Number of Participants With Grade 3+ Adverse Events Occurring More Than 30 Days After the Completion of Radiation Therapy

    National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.

    Time frame: From the end of radiation therapy (approximately 7-8 weeks from treatment start) to last follow-up. Median follow-up at time of analysis among surviving patients was 5.0 years.

  11. Testosterone Levels

    Testosterone levels will be reported at this time points.

    Time frame: 3, 6, 9, and 12 months

  12. Number of Participants With Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) Severity Score ≥ 3 (or Present) Occurring Within 30 Days After the Completion of RT

    PRO-CTCAE is a patient-reported outcome (PRO) measurement system developed to evaluate symptomatic toxicity in patients on cancer clinical trials, asking the patient about experience over the last seven days. Scores may reflect worst severity of the symptom (0=None, 1=Mild, 2=Moderate, 3=Severe, and 4=Very severe), frequency of the symptom (0=Never, 1=Rarely, 2=Occasionally, 3=Frequently, 4=Almost constantly), or the symptom's interference with one's "usual or daily activities" (0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit, 4=Very much). The symptom row title will indicate "Severity", "Frequency", or "Interference". All scores are compared between arms; statistical analysis results are entered for p-values \< 0.05.

    Time frame: Up to 5 years

  13. Number of Participants With Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) Severity Score ≥ 3 (or Present) Occurring More Thant 30 Days After the Completion of RT

    PRO-CTCAE is a patient-reported outcome (PRO) measurement system developed to evaluate symptomatic toxicity in patients on cancer clinical trials, asking the patient about experience over the last seven days. Scores may reflect worst severity of the symptom (0=None, 1=Mild, 2=Moderate, 3=Severe, and 4=Very severe), frequency of the symptom (0=Never, 1=Rarely, 2=Occasionally, 3=Frequently, 4=Almost constantly), or the symptom's interference with one's "usual or daily activities" (0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit, 4=Very much). The symptom row title will indicate "Severity", "Frequency", or "Interference". All scores are compared between arms; statistical analysis results are entered for p-values \< 0.05.

    Time frame: From the end of radiation therapy (approximately 7-8 weeks from treatment start) to two years.

07

Results

Posted Jul 10, 2026
Limitations and caveats
The study protocol defines the apalutamide arm (Arm 1) as the reference group for hazard ratios. However, the results presented here use the placebo arm (Arm 2) as the reference, consistent with the manuscript.

Participant flow

Participant flow — Overall Study
MilestoneArm 1 (Radiation Therapy, Apalutamide)Arm 2 (Radiation Therapy, Placebo)
Started143155
Eligible population141154
Completed141154
Not completed21
Withdrew: Protocol violation21

Outcome measures

PrimaryPercentage of Participants Alive Without Biochemical Progression (Biochemical Progression-free Survival)

Biochemical progression is defined as the first occurrence of the following: * A rise in PSA ≥0.2 ng/mL from nadir PSA, confirmed by a second PSA measurement equal to or higher than the first; * Clinical or radiographic local, regional, or distant metastases * Death from any cause. Biochemical progression-free survival rates are estimated using the Kaplan-Meier method, censoring participants alive at time of analysis. Arms are compared within molecular subtype group sequentially based on a study design that determines if and how to incorporate the biomarker in a in a subsequent phase III trial.

Time frame:
From randomization to biochemical progression or last follow-up if alive. Median follow-up at time of analysis among surviving patients was 5.0 years. Five-year rates are presented.
Reported as:
Number · Percentage of participants
Percentage of Participants Alive Without Biochemical Progression (Biochemical Progression-free Survival)
Percentage of participantsArm 1 (Radiation Therapy, Apalutamide)Arm 2 (Radiation Therapy, Placebo)
Luminal B72.4 (60.0 to 84.9)53.9 (40.9 to 66.9)
Luminal A/basal/unknown70.2 (59.2 to 81.3)71.1 (61.3 to 80.9)
Statistical analysis
  • Arm 1 (Radiation Therapy, Apalutamide) vs Arm 2 (Radiation Therapy, Placebo) · Log Rank · p = 0.0062 · Hazard ratio (hr): 0.45 · 80% CI 0.29 to 0.68Univariate HR; reference level = Arm 2
  • Arm 1 (Radiation Therapy, Apalutamide) vs Arm 2 (Radiation Therapy, Placebo) · Hazard ratio (hr): 0.96 · 80% CI 0.65 to 1.41Univariate HR; reference level = Arm 2
SecondaryPercentage of Participants Alive (Overall Survival)

Survival rates are estimated using the Kaplan-Meier method, censoring participants alive at time of analysis.

Time frame:
From randomization to death or last follow-up if alive. Median follow-up at time of analysis among surviving patients was 5.0 years. Five-year rates are presented.
Reported as:
Number · Percentage of participants
Percentage of Participants Alive (Overall Survival)
Percentage of participantsArm 1 (Radiation Therapy, Apalutamide)Arm 2 (Radiation Therapy, Placebo)
Percentage of Participants Alive (Overall Survival)96.0 (92.6 to 99.4)94.9 (91.3 to 98.6)
Statistical analysis
  • Arm 1 (Radiation Therapy, Apalutamide) vs Arm 2 (Radiation Therapy, Placebo) · Log Rank · p = 0.9852 (Two-sided significance level = 0.05) · Hazard ratio (hr): 0.99 · 95% CI 0.33 to 2.95Univariate HR; reference level = Arm 2
SecondaryPercentage of Participants Who Have Died Due to Prostate Cancer (Cancer-specific Mortality (CSM))

Prostate cancer death rates were estimated using the cumulative incidence method in which death from other causes is treated as a competing risk and alive patients are censored.

Time frame:
From the date of randomization to the date of death due to prostate cancer or last follow-up if alive. Median follow-up at time of analysis among surviving patients was 5.0 years. Five-year rates are presented.
Reported as:
Number · Percentage of participants
Percentage of Participants Who Have Died Due to Prostate Cancer (Cancer-specific Mortality (CSM))
Percentage of participantsArm 1 (Radiation Therapy, Apalutamide)Arm 2 (Radiation Therapy, Placebo)
Percentage of Participants Who Have Died Due to Prostate Cancer (Cancer-specific Mortality (CSM))0 (NA to NA)1.5 (0.3 to 4.9)
Statistical analysis
  • Arm 1 (Radiation Therapy, Apalutamide) vs Arm 2 (Radiation Therapy, Placebo) · Log Rank · p = 0.6788 (Two-sided significance level = 0.05) · Hazard ratio (hr): 0.60 · 95% CI 0.05 to 7.24Univariate subdistribution hazard ratio (sHR) estimated using the Fine-Gray proportinal subdistribution hazards model, with death from other cause treated as a competing risk. Reeference level = Arm 2.
SecondaryPercentage of Participants Alive Without Distant Metastases (Metastasis-free Survival (MFS))

Distant metastases are defined as clinical or radiographic appearance of disseminated disease. MFS rates are estimated using the Kaplan-Meier method, censoring participants alive without metastases at time of analysis.

Time frame:
From randomization to date of first distant metastasis or death, or last follow-up if alive. Median follow-up at time of analysis among surviving patients was 5.0 years. Five-year rates are presented.
Reported as:
Number · Percentage of participants
Percentage of Participants Alive Without Distant Metastases (Metastasis-free Survival (MFS))
Percentage of participantsArm 1 (Radiation Therapy, Apalutamide)Arm 2 (Radiation Therapy, Placebo)
Percentage of Participants Alive Without Distant Metastases (Metastasis-free Survival (MFS))92.1 (87.4 to 96.8)86.2 (80.5 to 91.8)
Statistical analysis
  • Arm 1 (Radiation Therapy, Apalutamide) vs Arm 2 (Radiation Therapy, Placebo) · Log Rank · p = 0.1644 · Hazard ratio (hr): 0.60 · 95% CI 0.29 to 1.25Univariate HR; reference level = Arm 1
SecondaryPercentage of Participants With Distant Metastasis

Distant metastases are defined as clinical or radiographic appearance of disseminated disease. Distant metastasis rates are estimated using the cumulative incidence method in which death is treated as competing risk and participants alive without distant metastases are censored at last known follow-up.

Time frame:
From randomization to date of first distant metastasis or death, or last follow-up if alive at time of analysis. Median follow-up at time of analysis was 5.0 years. Five-year rates are presented.
Reported as:
Number · Percentage of participants
Percentage of Participants With Distant Metastasis
Percentage of participantsArm 1 (Radiation Therapy, Apalutamide)Arm 2 (Radiation Therapy, Placebo)
Percentage of Participants With Distant Metastasis3.9 (1.5 to 8.4)10.3 (6.0 to 15.9)
Statistical analysis
  • Arm 1 (Radiation Therapy, Apalutamide) vs Arm 2 (Radiation Therapy, Placebo) · Log Rank · p = 0.0740 (Two-sided significance level = 0.05.) · Hazard ratio (hr): 0.43 · 95% CI 0.17 to 1.10Univariate subdistribution hazard ratio (sHR) estimated using the Fine-Gray proportinal subdistribution hazards model, with death from other cause treated as a competing risk. Reference level = Arm 2.
SecondaryPercentage of Participants Wtih Local-regional Progression

Local-regional progression is defined as recurrence within the pelvis including lymph nodes below the iliac bifurcation. Local-regional progression rates are estimated using the cumulative incidence method in which death is treated as competing risk and participants alive without local-regional progression are censored at last known follow-up.

Time frame:
From randomization to date of first local or regional recurrence or death, or last follow-up if alive at time of analysis. Median follow-up at time of analysis was 5.0 years. Five-year rates are presented.
Reported as:
Number · Percentage of participants
Percentage of Participants Wtih Local-regional Progression
Percentage of participantsArm 1 (Radiation Therapy, Apalutamide)Arm 2 (Radiation Therapy, Placebo)
Percentage of Participants Wtih Local-regional Progression8.2 (4.2 to 13.9)10.4 (6.1 to 16.0)
Statistical analysis
  • Arm 1 (Radiation Therapy, Apalutamide) vs Arm 2 (Radiation Therapy, Placebo) · Log Rank · p = 0.5961 (Two-side significance level = 0.05) · Hazard ratio (hr): 0.81 · 95% CI 0.37 to 1.75Univariate subdistribution hazard ratio (sHR) estimated using the Fine-Gray proportinal subdistribution hazards model, with death from other causes treated as a competing risk. Reference level = Arm 2.
SecondaryPSA Nadir During First Year of Treatment and Prior to Initiation of Any Hormonal Salvage Therapy

Will be compared between the two groups using a two-sample t-test.

Time frame:
First year of treatment
Reported as:
Mean · mg/mL
PSA Nadir During First Year of Treatment and Prior to Initiation of Any Hormonal Salvage Therapy
mg/mLArm 1 (Radiation Therapy, Apalutamide)Arm 2 (Radiation Therapy, Placebo)
PSA Nadir During First Year of Treatment and Prior to Initiation of Any Hormonal Salvage Therapy0.042 ± 0.0410.091 ± 0.118
Statistical analysis
  • Arm 1 (Radiation Therapy, Apalutamide) vs Arm 2 (Radiation Therapy, Placebo) · t-test, 2 sided · p = <0.0001
SecondaryPercentage of Participants That Started Salvage Hormonal Therapy

Initiation of salvage hormone therapy (LHRH analogues or non-study anti-androgens) that occurs after completion of SRT. Salvage hormonal therapy rates are estimated using the cumulative incidence method in which death is treated as competing risk and participants alive who have not started salvage hormonal therapy are censored at last known follow-up.

Time frame:
From randomization to initiation of salvage hormonal therapy or death, whichever occurs first, or last follow-up if alive at time of analysis. Median follow-up at time of analysis among surviving patients was 5.0 years. Five-year rates are presented.
Reported as:
Number · Percentage of participants
Percentage of Participants That Started Salvage Hormonal Therapy
Percentage of participantsArm 1 (Radiation Therapy, Apalutamide)Arm 2 (Radiation Therapy, Placebo)
Percentage of Participants That Started Salvage Hormonal Therapy5.5 (2.4 to 10.4)18.8 (12.9 to 25.7)
Statistical analysis
  • Arm 1 (Radiation Therapy, Apalutamide) vs Arm 2 (Radiation Therapy, Placebo) · Log Rank · p = 0.0042 (Two-sided significance level = 0.05.) · Hazard ratio (hr): 0.36 · 95% CI 0.18 to 0.74Univariate subdistribution hazard ratio (sHR) estimated using the Fine-Gray proportinal subdistribution hazards model, with death from other causes treated as a competing risk. Reference level = Arm 2.
SecondaryProportion of Participants With Undetectable PSA (< 0.1) and Non-castrate Testosterone (≥ 50 ng/dl) at One and Three Years
Time frame:
One and three years

Results for this outcome have not been posted.

SecondaryNumber of Participants With Grade 3+ Adverse Events Occurring Within 30 Days After the Completion of RT

National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.

Time frame:
Up to 30 days after radiation therapy, which lasts approximately 7-8 weeks from treatment start.

Results for this outcome have not been posted.

SecondaryNumber of Participants With Grade 3+ Adverse Events Occurring More Than 30 Days After the Completion of Radiation Therapy

National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.

Time frame:
From the end of radiation therapy (approximately 7-8 weeks from treatment start) to last follow-up. Median follow-up at time of analysis among surviving patients was 5.0 years.

Results for this outcome have not been posted.

SecondaryTestosterone Levels

Testosterone levels will be reported at this time points.

Time frame:
3, 6, 9, and 12 months

Results for this outcome have not been posted.

SecondaryNumber of Participants With Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) Severity Score ≥ 3 (or Present) Occurring Within 30 Days After the Completion of RT

PRO-CTCAE is a patient-reported outcome (PRO) measurement system developed to evaluate symptomatic toxicity in patients on cancer clinical trials, asking the patient about experience over the last seven days. Scores may reflect worst severity of the symptom (0=None, 1=Mild, 2=Moderate, 3=Severe, and 4=Very severe), frequency of the symptom (0=Never, 1=Rarely, 2=Occasionally, 3=Frequently, 4=Almost constantly), or the symptom's interference with one's "usual or daily activities" (0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit, 4=Very much). The symptom row title will indicate "Severity", "Frequency", or "Interference". All scores are compared between arms; statistical analysis results are entered for p-values \< 0.05.

Time frame:
Up to 5 years

Results for this outcome have not been posted.

SecondaryNumber of Participants With Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) Severity Score ≥ 3 (or Present) Occurring More Thant 30 Days After the Completion of RT

PRO-CTCAE is a patient-reported outcome (PRO) measurement system developed to evaluate symptomatic toxicity in patients on cancer clinical trials, asking the patient about experience over the last seven days. Scores may reflect worst severity of the symptom (0=None, 1=Mild, 2=Moderate, 3=Severe, and 4=Very severe), frequency of the symptom (0=Never, 1=Rarely, 2=Occasionally, 3=Frequently, 4=Almost constantly), or the symptom's interference with one's "usual or daily activities" (0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit, 4=Very much). The symptom row title will indicate "Severity", "Frequency", or "Interference". All scores are compared between arms; statistical analysis results are entered for p-values \< 0.05.

Time frame:
From the end of radiation therapy (approximately 7-8 weeks from treatment start) to two years.

Results for this outcome have not been posted.

Adverse events

Collected over From randomization to last follow-up. Median follow-up at time of analysis was 5.0 years.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Arm 1 (Radiation Therapy, Apalutamide)6/141 (4.3%)8/141 (5.7%)134/141 (95%)
Arm 2 (Radiation Therapy, Placebo)7/154 (4.5%)8/154 (5.2%)140/154 (90.9%)
Most frequent serious events
Showing 10 of 28
Most frequent serious events
EventArm 1 (Radiation Therapy, Apalutamide)Arm 2 (Radiation Therapy, Placebo)
Rash maculo-papularSkin and subcutaneous tissue disorders3/1410/154
Urinary tract infectionInfections and infestations2/1410/154
Neutrophil count decreasedInvestigations2/1410/154
Atrial fibrillationCardiac disorders1/1412/154
Febrile neutropeniaBlood and lymphatic system disorders1/1410/154
DiarrheaGastrointestinal disorders1/1410/154
Mucositis oralGastrointestinal disorders1/1410/154
Small intestinal obstructionGastrointestinal disorders1/1410/154
ChillsGeneral disorders1/1410/154
Infections and infestations - OtherInfections and infestations1/1410/154
Most frequent other events
Showing 10 of 52
Most frequent other events
EventArm 1 (Radiation Therapy, Apalutamide)Arm 2 (Radiation Therapy, Placebo)
FatigueGeneral disorders91/14178/154
Urinary frequencyRenal and urinary disorders74/14158/154
DiarrheaGastrointestinal disorders57/14166/154
Urinary incontinenceRenal and urinary disorders57/14152/154
Urinary urgencyRenal and urinary disorders53/14143/154
Erectile dysfunctionReproductive system and breast disorders36/14143/154
HypertensionVascular disorders36/14132/154
Breast painReproductive system and breast disorders35/1410/154
Rash maculo-papularSkin and subcutaneous tissue disorders35/14115/154
GynecomastiaReproductive system and breast disorders34/1414/154

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Arm 1 (Radiation Therapy, Apalutamide)Arm 2 (Radiation Therapy, Placebo)Total
Median65 (59 to 71)65.5 (60 to 70)65 (59 to 70)
Sex: Female, Male
Sex: Female, Male(Participants)Arm 1 (Radiation Therapy, Apalutamide)Arm 2 (Radiation Therapy, Placebo)Total
Female000
Male141154295
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Arm 1 (Radiation Therapy, Apalutamide)Arm 2 (Radiation Therapy, Placebo)Total
American Indian or Alaska Native000
Asian314
Native Hawaiian or Other Pacific Islander011
Black or African American92231
White126129255
More than one race202
Unknown or Not Reported112
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Arm 1 (Radiation Therapy, Apalutamide)Arm 2 (Radiation Therapy, Placebo)Total
Hispanic or Latino437
Not Hispanic or Latino137148285
Unknown or Not Reported033
Surgical margins
Surgical margins(Participants)Arm 1 (Radiation Therapy, Apalutamide)Arm 2 (Radiation Therapy, Placebo)Total
Negative7474148
Positive6780147
Pre-RT Prostate-specific Antigen (PSA)
Pre-RT Prostate-specific Antigen (PSA)(ng/mL)Arm 1 (Radiation Therapy, Apalutamide)Arm 2 (Radiation Therapy, Placebo)Total
Median0.2 (0.14 to 0.31)0.21 (0.15 to 0.33)0.2 (0.14 to 0.32)
Pre-RT PSA Category
Pre-RT PSA Category(Participants)Arm 1 (Radiation Therapy, Apalutamide)Arm 2 (Radiation Therapy, Placebo)Total
< 0.5 ng/mL125130255
0.5 - 1.0 ng/mL162440
Combined Gleason Score
Combined Gleason Score(Participants)Arm 1 (Radiation Therapy, Apalutamide)Arm 2 (Radiation Therapy, Placebo)Total
6112
7116120236
891423
9141933
10101

5 further baseline measures are reported on the registry.

08

Study locations

360 sites

Showing the first 100 of 360 sites across 2 countries. Choose a country and city above to see the rest.

09

References and documents

Publications

  • Morgan TM, Boorjian SA, Buyyounouski MK, Chapin BF, Chen DYT, Cheng HH, Chou R, Jacene HA, Kamran SC, Kim SK, Kirkby E, Luckenbaugh AN, Nathanson BJ, Nyame YA, Posadas EM, Tran PT, Chen RC. Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part III: Salvage Therapy After Radiotherapy or Focal Therapy, Pelvic Nodal Recurrence and Oligometastasis, and Future Directions. J Urol. 2024 Apr;211(4):526-532. doi: 10.1097/JU.0000000000003890. Epub 2024 Feb 29. PubMed 38421252 ↗
  • Morgan TM, Boorjian SA, Buyyounouski MK, Chapin BF, Chen DYT, Cheng HH, Chou R, Jacene HA, Kamran SC, Kim SK, Kirkby E, Luckenbaugh AN, Nathanson BJ, Nyame YA, Posadas EM, Tran PT, Chen RC. Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part II: Treatment Delivery for Non-metastatic Biochemical Recurrence After Primary Radical Prostatectomy. J Urol. 2024 Apr;211(4):518-525. doi: 10.1097/JU.0000000000003891. Epub 2024 Feb 29. PubMed 38421243 ↗

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: Yes — NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

Data sharing details ↗ · grants.nih.gov

10

Updates

1 registry update since Sep 25, 2026
Results
Posted results revised
revised Oct 1, 2026
Sites
1 site added, 1 site removed
Show site
  • Sands Cancer Center · Canandaigua, United States
Show 1 removed
  • Sands Cancer Center · Canandiaqua, United States
Oct 1, 2026
Study completion
Oct 27, 2026→Mar 10, 2030
Oct 1, 2026
Show all 1 update
  1. Oct 1, 2026
    Posted results revised
    1 site added, 1 site removed
    Show site
    • Sands Cancer Center · Canandaigua, United States
    Show 1 removed
    • Sands Cancer Center · Canandiaqua, United States
    Study completion Oct 27, 2026→Mar 10, 2030

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

11

Registry details

Key details

Study ID
NCT03371719
Lead sponsor
NRG Oncology
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Dec 13, 2017
Start date
Jun 20, 2018
Primary completion
Mar 10, 2025
Completion
Mar 10, 2030 (estimated)
Results posted
Jul 10, 2026
Last update
Oct 1, 2026

Study contacts

Felix Y Feng
principal investigator · NRG Oncology

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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