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Active, not recruitingNCT03371719Updated Aug 28, 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 2026-08-28.

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

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

Who can participate

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

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
  • Karnofsky 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
  • Hemoglobin >= 9.0 g/dL, independent of transfusion and/or growth factors within 90 days prior to Step 1 registration
  • Platelet 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
  • Glomerular filtration rate (GFR) >= 35 mL/min estimated by Cockcroft-Gault or measured directly by 24 hour urine creatinine within 90 days prior to Step 1 registration
  • Serum total bilirubin =\< 1.5 x upper limit of normal (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
  • Aspartate aminotransferase (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 birth control if he is having sex with a woman of childbearing potential 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 informed consent prior to study entry

Exclusion criteria

Exclusion Criteria:

  • PRIOR TO STEP 1 REGISTRATION:
  • Definitive clinical, radiologic, or pathologic evidence of metastatic disease (M1) or lymph node involvement (N1)
  • Prior invasive malignancy (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., human immunodeficiency virus [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 CD4 count \< 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 immunosuppressive 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
04

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

05

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.

06

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 disorders and administration site conditions1/1410/154
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 disorders and administration site conditions91/14178/154
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.

07

Study locations

360 sites
  • Arizona Center for Cancer Care - Gilbert
    Gilbert, Arizona 85297, United States
  • Arizona Center for Cancer Care-Peoria
    Peoria, Arizona 85381, United States
  • Arizona Center for Cancer Care - Scottsdale
    Scottsdale, Arizona 85258, United States
  • Arizona Center for Cancer Care-Surprise
    Surprise, Arizona 85374, United States
  • University of Arkansas for Medical Sciences
    Little Rock, Arkansas 72205, United States
  • Alta Bates Summit Medical Center-Herrick Campus
    Berkeley, California 94704, United States
  • Marin General Hospital
    Greenbrae, California 94904, United States
  • Los Angeles General Medical Center
    Los Angeles, California 90033, United States
  • USC / Norris Comprehensive Cancer Center
    Los Angeles, California 90033, United States
  • Cedars Sinai Medical Center
    Los Angeles, California 90048, United States
  • Sutter Cancer Centers Radiation Oncology Services-Roseville
    Roseville, California 95661, United States
  • Sutter Medical Center Sacramento
    Sacramento, California 95816, United States
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California 95817, United States
  • Gene Upshaw Memorial Tahoe Forest Cancer Center
    Truckee, California 96161, United States
  • Sutter Solano Medical Center/Cancer Center
    Vallejo, California 94589, United States
  • UCHealth University of Colorado Hospital
    Aurora, Colorado 80045, United States
  • Penrose-Saint Francis Healthcare
    Colorado Springs, Colorado 80907, United States
  • UCHealth Memorial Hospital Central
    Colorado Springs, Colorado 80909, United States
  • Memorial Hospital North
    Colorado Springs, Colorado 80920, United States
  • Poudre Valley Hospital
    Fort Collins, Colorado 80524, United States
  • Cancer Care and Hematology-Fort Collins
    Fort Collins, Colorado 80528, United States
  • Valley View Hospital Cancer Center
    Glenwood Springs, Colorado 81601, United States
  • UCHealth Greeley Hospital
    Greeley, Colorado 80631, United States
  • Medical Center of the Rockies
    Loveland, Colorado 80538, United States
  • Stamford Hospital/Bennett Cancer Center
    Stamford, Connecticut 06904, United States
  • Helen F Graham Cancer Center
    Newark, Delaware 19713, United States
  • Christiana Care Health System-Christiana Hospital
    Newark, Delaware 19718, United States
  • Beebe Health Campus
    Rehoboth Beach, Delaware 19971, United States
  • George Washington University Medical Center
    Washington D.C., District of Columbia 20037, United States
  • AdventHealth Altamonte
    Altamonte Springs, Florida 32701, United States
  • Regional Cancer Center-Lee Memorial Health System
    Fort Myers, Florida 33905, United States
  • AdventHealth Kissimmee
    Kissimmee, Florida 34744, United States
  • AdventHealth Orlando
    Orlando, Florida 32803, United States
  • AdventHealth East Orlando
    Orlando, Florida 32822, United States
  • Cleveland Clinic-Weston
    Weston, Florida 33331, United States
  • AdventHealth Winter Park
    Winter Park, Florida 32792, United States
  • Grady Health System
    Atlanta, Georgia 30303, United States
  • Emory University Hospital Midtown
    Atlanta, Georgia 30308, United States
  • Emory University Hospital/Winship Cancer Institute
    Atlanta, Georgia 30322, United States
  • Emory Saint Joseph's Hospital
    Atlanta, Georgia 30342, United States
  • Northside Hospital
    Atlanta, Georgia 30342, United States
  • Augusta University Medical Center
    Augusta, Georgia 30912, United States
  • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
    Savannah, Georgia 31405, United States
  • Saint Luke's Cancer Institute - Boise
    Boise, Idaho 83712, United States
  • Saint Luke's Cancer Institute - Fruitland
    Fruitland, Idaho 83619, United States
  • Saint Luke's Cancer Institute - Meridian
    Meridian, Idaho 83642, United States
  • Saint Luke's Cancer Institute - Nampa
    Nampa, Idaho 83687, United States
  • Saint Luke's Cancer Institute - Twin Falls
    Twin Falls, Idaho 83301, United States
  • Rush MD Anderson Cancer Center
    Chicago, Illinois 60612, United States
  • University of Illinois
    Chicago, Illinois 60612, United States
  • Decatur Memorial Hospital
    Decatur, Illinois 62526, United States
  • Crossroads Cancer Center
    Effingham, Illinois 62401, United States
  • Edward Hines Jr VA Hospital
    Hines, Illinois 60141, United States
  • Loyola University Medical Center
    Maywood, Illinois 60153, United States
  • Illinois CancerCare-Peoria
    Peoria, Illinois 61615, United States
  • OSF Saint Francis Radiation Oncology at Peoria Cancer Center
    Peoria, Illinois 61615, United States
  • OSF Saint Francis Medical Center
    Peoria, Illinois 61637, United States
  • Southern Illinois University School of Medicine
    Springfield, Illinois 62702, United States
  • Springfield Clinic
    Springfield, Illinois 62702, United States
  • Springfield Memorial Hospital
    Springfield, Illinois 62781, United States
  • Carle Cancer Center
    Urbana, Illinois 61801, United States
  • Parkview Hospital Randallia
    Fort Wayne, Indiana 46805, United States
  • Parkview Regional Medical Center
    Fort Wayne, Indiana 46845, United States
  • Goshen Center for Cancer Care
    Goshen, Indiana 46526, United States
  • Reid Health
    Richmond, Indiana 47374, United States
  • Mercy Cancer Center-West Lakes
    Clive, Iowa 50325, United States
  • UI Health Care Mission Cancer and Blood - West Des Moines Clinic
    Clive, Iowa 50325, United States
  • Greater Regional Medical Center
    Creston, Iowa 50801, United States
  • Mercy Medical Center - Des Moines
    Des Moines, Iowa 50314, United States
  • UI Health Care Mission Cancer and Blood - Laurel Clinic
    Des Moines, Iowa 50314, United States
  • Mercy Medical Center-West Lakes
    West Des Moines, Iowa 50266, United States
  • University of Kansas Cancer Center
    Kansas City, Kansas 66160, United States
  • The University of Kansas Cancer Center - Olathe
    Olathe, Kansas 66061, United States
  • University of Kansas Cancer Center-Overland Park
    Overland Park, Kansas 66210, United States
  • Salina Regional Health Center
    Salina, Kansas 67401, United States
  • University of Kansas Hospital-Westwood Cancer Center
    Westwood, Kansas 66205, United States
  • University of Kentucky/Markey Cancer Center
    Lexington, Kentucky 40536, United States
  • Mary Bird Perkins Cancer Center
    Baton Rouge, Louisiana 70809, United States
  • East Jefferson General Hospital
    Metairie, Louisiana 70006, United States
  • LSU Healthcare Network / Metairie Multi-Specialty Clinic
    Metairie, Louisiana 70006, United States
  • MaineHealth Coastal Cancer Treatment Center
    Bath, Maine 04530, United States
  • MaineHealth Waldo Hospital
    Belfast, Maine 04915, United States
  • MaineHealth Maine Medical Center - Biddeford
    Biddeford, Maine 04005, United States
  • Lafayette Family Cancer Center-EMMC
    Brewer, Maine 04412, United States
  • MaineHealth Stephens Hospital
    Norway, Maine 04268, United States
  • MaineHealth Maine Medical Center - Portland
    Portland, Maine 04102, United States
  • Penobscot Bay Medical Center
    Rockport, Maine 04856, United States
  • MaineHealth Cancer Care and IV Therapy - Sanford
    Sanford, Maine 04073, United States
  • MaineHealth Cancer Care Center of York County
    Sanford, Maine 04073, United States
  • MaineHealth Maine Medical Center- Scarborough
    Scarborough, Maine 04074, United States
  • MaineHealth Cancer Care and IV Therapy - South Portland
    South Portland, Maine 04106, United States
  • University of Maryland/Greenebaum Cancer Center
    Baltimore, Maryland 21201, United States
  • Saint Agnes Hospital
    Baltimore, Maryland 21229, United States
  • Central Maryland Radiation Oncology in Howard County
    Columbia, Maryland 21044, United States
  • UM Baltimore Washington Medical Center/Tate Cancer Center
    Glen Burnie, Maryland 21061, United States
  • Lahey Hospital and Medical Center
    Burlington, Massachusetts 01805, United States
  • Lowell General Hospital
    Lowell, Massachusetts 01854, United States
  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
    Ann Arbor, Michigan 48106, United States
  • University of Michigan Rogel Cancer Center
    Ann Arbor, Michigan 48109, United States
  • Bronson Battle Creek
    Battle Creek, Michigan 49017, United States

Showing the first 100 of 360 sites across 2 countries.

08

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

  • Protocol and statistical analysis plan · Sep 24, 2020
  • Informed consent form · Sep 24, 2020

Documents are hosted by the registry — open the source record to download them.

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

09

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
Oct 27, 2026 (estimated)
Results posted
Jul 10, 2026
Last update
Aug 28, 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 ↗

Not currently enrolling

This study is active, not recruiting, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.

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