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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
298
Given PO
Undergo external beam radiation therapy
Given PO
Arizona Center for Cancer Care - Gilbert
Gilbert, Arizona, United States
Arizona Center for Cancer Care-Peoria
Peoria, Arizona, United States
Arizona Center for Cancer Care - Scottsdale
Scottsdale, Arizona, United States
Arizona Center for Cancer Care-Surprise
Surprise, Arizona, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
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.
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.
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.
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.
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.
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.
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
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.
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
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.
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.
Testosterone Levels
Testosterone levels will be reported at this time points.
Time frame: 3, 6, 9, and 12 months
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
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.
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