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RecruitingNCT04423211Updated Aug 19, 2026

Treating Prostate Cancer That Has Come Back After Surgery With Apalutamide and Targeted Radiation Based on PET Imaging

A Phase 3 interventional study of 3-Dimensional Conformal Radiation Therapy and Apalutamide in Biochemically Recurrent Prostate Carcinoma, Metastatic Prostate Carcinoma and Prostate Adenocarcinoma, sponsored by ECOG-ACRIN Cancer Research Group. Recruiting at 341 sites in United States. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-19.

Sponsored by ECOG-ACRIN Cancer Research Group · Phase 3, Interventional, and Treatment

From the registry’s dates

  • Started Oct 2020; still recruiting 5 years 11 months later.
Phase
Phase 3
Study type
Interventional
Enrollment
804
Allocation
Randomized
Ages
18 Years and older
Sex
Male
01

Study summary

This phase III trial tests two questions by two separate comparisons of therapies. The first question is whether enhanced therapy (apalutamide in combination with abiraterone + prednisone) added to standard of care (prostate radiation therapy and short term androgen deprivation) is more effective compared to standard of care alone in patients with prostate cancer who experience biochemical recurrence (a rise in the blood level of prostate specific antigen [PSA] after surgical removal of the prostate cancer).

A second question tests treatment in patients with biochemical recurrence who show prostate cancer spreading outside the pelvis (metastasis) by positron emission tomography (PET) imaging. In these patients, the benefit of adding metastasis-directed radiation to enhanced therapy (apalutamide in combination with abiraterone + prednisone) is tested.

Diagnostic procedures, such as PET, may help doctors look for cancer that has spread to the pelvis. Androgens are hormones that may cause the growth of prostate cancer cells. Apalutamide may help fight prostate cancer by blocking the use of androgens by the tumor cells. Metastasis-directed targeted radiation therapy uses high energy rays to kill tumor cells and shrink tumors that have spread. This trial may help doctors determine if using PET results to deliver more tailored treatment (i.e., adding apalutamide, with or without targeted radiation therapy, to standard of care treatment) works better than standard of care treatment alone in patients with biochemical recurrence of prostate cancer.

Read the detailed description

PRIMARY OBJECTIVES:

I. For patients without PET-evidence of extrapelvic metastases, to evaluate whether the addition of enhanced systemic therapy to standard of care (SOC) salvage radiation therapy (RT) could prolong progression-free survival (PFS).

II. For patients with PET-evidence of extrapelvic metastases, to evaluate whether the addition of metastasis-directed RT to enhanced systemic therapy and SOC salvage RT could prolong PFS.

III. To compare overall quality of life, measured by Functional Assessment of Cancer Therapy - Prostate (FACT-P) total score, at 6 months between the two sets of treatment arms (A with B and C with D). (QUALITY OF LIFE [QOL] OBJECTIVE)

SECONDARY OBJECTIVES:

I. To evaluate overall survival in each arm. II. To evaluate event-free survival in each arm. III. To evaluate time to prostate-specific antigen (PSA) progression in each arm.

IV. To assess the incidence of adverse events with the addition of enhanced systemic therapy in patients without PET-evidence of extrapelvic metastases.

V. To assess the incidence of adverse events with local ablative metastasis-directed RT for PET-positive metastatic disease in patients with PET-evidence of extrapelvic metastases.

VI. To estimate the detection rate of PET at the patient and regional level, and to evaluate its concordance with the follow-up Food and Drug Administration (FDA)-approved conventional imaging modalities (CIM) (as available) considered standard-of-care per institution, including computed tomography (CT), bone scintigraphy, magnetic resonance imaging (MRI) and PET imaging.

VII. To determine the distribution of PET-positive lesions among anatomic sites (prostate fossa, intrapelvic soft tissue/lymph node, extrapelvic soft tissue/lymph node, and bone metastases) in patients with post-radical prostatectomy (RP) biochemical recurrence (BCR), correlated with PSA (level, doubling time, velocity) and other relevant clinical parameters.

VIII. To compare the change in overall QOL, measured by FACT-P total score, from baseline to 6 months between the two sets of treatment arms (A with B and C with D). (QOL OBJECTIVE) IX. To compare patient-reported fatigue (Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue scores) at 6 months between the two sets of treatment arms (A with B and C with D). (QOL OBJECTIVE) X. To compare patient-reported overall QOL (FACT-P scores), fatigue (FACIT-Fatigue scores) and pain interference (patient reported outcomes measurement information system [PROMIS] Pain Interference Short Form 4a) between the two sets of treatment arms (A with B and C with D) at the time of disease progression. (QOL OBJECTIVE)

EXPLORATORY OBJECTIVES:

I.To determine the value of repeat PET (PET2) at time of second PSA progression, clinical concern for progression, or 12 months after completion of enhanced systemic therapy, whichever comes first to assess response to therapy (enhanced systemic therapy +/- focal RT and/or androgen deprivation therapy [ADT]) compared to available standard response assessments (PSA and conventional imaging modalities [CIM]).

II. To compare cognitive function, measured by FACT - cognitive function (Cog) peritoneal cancer index (PCI) and total scores, between the three treatment arms receiving enhanced systemic treatment with ADT and apalutamide (Arms B, C, and D) and antiandrogen therapy (ADT) alone (Arm A) at 6 and 12 month. (QOL OBJECTIVE) III. To compare the change in cognitive function, measured by change in FACT-Cog PCI and total scores, from baseline to 6 and baseline to 12 months, between the three treatment arms receiving enhanced systemic treatment with ADT and apalutamide (Arms B, C, and D) and ADT alone (Arm A) at 6 and 12 months. (QOL OBJECTIVE) IV. To characterize longitudinal change in cognitive function between baseline and 24 months in patients with prostate cancer receiving treatment for biochemical recurrence (BCR) and define clinical and disease related characteristics associated with greater cognitive change by the FACT-Cog PCI and total scores. (QOL OBJECTIVE)

OUTLINE:

STEP 0: Patients undergo SOC PET/CT or PET/MR scan at baseline. Patients randomized to Arms C or D and receiving fluciclovine F18 intravenously (IV) undergo a repeat PET2 at time of PSA progression or clinical concerns for progression or 12 months after completion of enhanced systemic therapy, whichever occurs first. Patients in Arm C or D using another tracer for PET1 do not undergo PET2.

STEP 1: Patients are randomized to 1 of 4 arms based on results of fluciclovine F18 PET/CT or PET/MR in Step 0.

ARM A (PET NEGATIVE FOR EXTRA PELVIC-METASTASES): Patients undergo SOC external beam radiation therapy (EBRT) for 6 months. Patients also receive goserelin acetate subcutaneously (SC), leuprolide acetate intramuscularly (IM), triptorelin IM, relugolix orally (PO), or degarelix SC for 6 months starting up to 3 months prior to EBRT but no later than 7 days after start of EBRT. All treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.

ARM B (PET NEGATIVE FOR EXTRA PELVIC-METASTASES): Patients undergo SOC EBRT and receive goserelin acetate SC, leuprolide acetate IM, triptorelin IM, relugolix PO, or degarelix SC as in Arm A. Patients also receive apalutamide PO once daily (QD) for 6 months in the absence of disease progression or unacceptable toxicity.

ARM C: (PET POSITIVE FOR EXTRA PELVIC-METASTASES): Patients undergo SOC EBRT and receive goserelin acetate SC, leuprolide acetate IM, triptorelin IM, relugolix PO, or degarelix SC as in Arm A. Patients also receive apalutamide PO QD as in Arm B.

ARM D (PET POSITIVE FOR EXTRA PELVIC-METASTASES): Patients undergo SOC EBRT and receive goserelin acetate SC, leuprolide acetate IM, triptorelin IM, relugolix PO, or degarelix SC as in Arm A and apalutamide PO QD as in Arm B. Patients also undergo stereotactic body radiation therapy (SBRT) or 3-dimensional (3D) conformal radiation therapy (CRT), intensity-modulated radiation therapy (IMRT) (including volume modulated arc therapy [VMAT]), and intensity-modulated proton therapy (IMPT) over 3-10 fractions in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for the first 2 years, every 6 months for years 3-5, and then annually for years 6-10.

02

Conditions studied

  • Biochemically Recurrent Prostate Carcinoma
  • Metastatic Prostate Carcinoma
  • Prostate Adenocarcinoma
  • Stage IVB Prostate Cancer AJCC v8

Browse trials for

03

In context

Prostatic Neoplasms

6,367 studies on the registry are indexed under Prostatic Neoplasms; 1,397 are open to participants now.

This study's planned enrollment of 804 is above the median of 58 across 4,821 interventional studies indexed under Prostatic Neoplasms.

Browse Prostatic Neoplasms studies →

Lead sponsor

ECOG-ACRIN Cancer Research Group is the lead sponsor of 118 studies on the registry; 13 are open to participants now.

Of its 13 completed or terminated interventional studies of FDA-regulated products, 13 (100%) have results posted.

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

Eligibility criteria

Inclusion Criteria:

  • STEP 0: REGISTRATION ELIGIBILITY CRITERIA
  • Patient must be male and >= 18 years of age.
  • Patient must have had a radical prostatectomy (RP) as definitive therapy for histopathologically-proven prostatic adenocarcinoma

  • Patient must have biochemical recurrence (BCR) after RP, defined as follows:

    • If time to BCR, defined as time to first detectable PSA ( > lower limit of normal for assay used) after RP, is \< 12 months, a minimum PSA level of >= 0.2 ng/mL and a confirmatory reading of >= 0.2 ng/mL is required, per the American Urological Association (AUA) definition (Note: patients with a persistent PSA reading of at least 0.2 ng/mL are eligible)
    • If time to BCR, defined as time to first detectable PSA (> lower limit of normal for assay used) after RP, is >= 12 months, a minimum absolute PSA of 0.5 ng/mL is required
    • If the patient has a detectable PSA (> lower limit of normal for assay used) at any time after RP AND has an eligible baseline SOC PET (PET1) with at least one positive lesion in any location, then there is no minimum PSA requirement

  • Patients must have no definite evidence for extrapelvic metastatic disease by conventional imaging modalities (CIM) (CT abdomen/pelvis or MRI abdomen/pelvis AND bone scintigraphy, or equivalent), within 26 weeks prior to Step 0 registration. If a patient only has a study-eligible PET/CT or PET/MR (i.e., PET done without prior CIM): if the PET is negative for extrapelvic lesions, then baseline CIM is NOT required. If the PET positive for extrapelvic lesions, then patient should have a baseline CT/MRI for soft tissue lesions and/or a bone scan for osseous lesions

    • Study eligible = PET using FDA-approved radiotracer and performed within 16 weeks prior to study registration
  • Extra-pelvic metastases is defined as any osseous metastases and/or any extrapelvic soft tissue, lymph nodes and organ metastases; extra-pelvic is defined as superior to common iliac bifurcation, outside of standard prostate bed + whole pelvis nodal RT fields. Baseline PET/CT or PET/MR scan (PET1) is eligible for this study if the SOC PET scan is completed with an FDA approved radiotracer for prostate cancer after Step 0 registration and prior to Step 1 randomization OR up to 16 weeks prior to Step 0 registration
  • Patient must be a candidate for SOC post-prostatectomy radiation therapy (RT) to the prostate bed and pelvic nodes with androgen deprivation therapy (ADT)
  • Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Patient must not have started ADT for biochemical recurrence prior to baseline PET (PET1) imaging. A short course of low-dose anti-androgen such as bicalutamide, given after baseline study PET/CT but prior to study registration, is permitted as a brief temporizing measure in advance of starting protocol-approved SOC ADT.
  • Patient must not be enrolled in another therapeutic clinical trial
  • Patient must be able to lie flat and still for approximately 20-30 minutes or otherwise tolerate a PET scan and radiation treatment planning and delivery
  • Patients undergoing a PET/MR must meet local institutional safety guidelines for MRI
  • Patient must not have history of seizures or known condition that may cause predisposal to seizures (e.g., stroke or head trauma resulting in loss of consciousness) within 1 year prior to registration
  • Patient must not have history of inflammatory bowel disease or any gastrointestinal disorder affecting absorption that is expected to increase risk of complication from radiotherapy
  • Hemoglobin (Hgb) >= 9.0 g/dL (independent of transfusion and/or growth factors within 3 months prior to Step 0 registration) (obtained within 8 weeks prior to Step 0 registration)
  • Leukocytes >= 3,000/mcL (obtained within 8 weeks prior to Step 0 registration)
  • Absolute neutrophil count >= 1,500/mcL (obtained within 8 weeks prior to Step 0 registration)
  • Platelets >= 100,000/mcL (obtained within 8 weeks prior to Step 0 registration)
  • Total bilirubin \< 1.5 x institutional upper limit of normal (ULN) (patients with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, must have a direct bilirubin of \< 1.5 x ULN to be eligible) (obtained within 8 weeks prior to Step 0 registration)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =\< 2.5 x institutional ULN (obtained within 8 weeks prior to Step 0 registration)
  • Creatine \< 1.5 x instituional ULN (or measured creatinine clearance > 30 mL/min)
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class I or II (by patient symptoms) or A or B (by objective assessment)
  • Patient must not have completed a course of prior pelvic radiation therapy for any reason
  • Patient must agree not to father children while on study

  • Patient must be English or Spanish speaking to be eligible for the QOL component of the study

    • NOTE: Sites cannot translate the associated QOL forms
  • STEP 1: RANDOMIZATION ELIGIBILITY CRITERIA
  • Patient must have completed a baseline SOC PET/CT or PET/MR (PET1 scan) using FDA approved radiotracer with results of extra-pelvic metastases involvement known (positive or negative). The PET1 must have been completed after Step 0 registration and prior to Step 1 randomization OR up to 12 weeks prior to Step 0 registration
  • For patients with negative extra-pelvic metastases, PET-imaging status of intra-pelvic nodes must be known (positive or negative)
  • For patients with positive extra-pelvic metastases (defined as any PET positive lesions outside of standard salvage RT fields [prostate bed +/- typical whole pelvis]), the number of extra-pelvic lesions must be known (1 - 5 or > 5 extra-pelvic lesions)
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
804 participants (estimated)

Study arms

  • Active comparator
    Arm A (EBRT, short-term androgen deprivation therapy [STAD])

    STEP 0: Patients undergo SOC PET/CT or PET/MR scan at baseline. Patients randomized to Arms C or D and receiving fluciclovine F18 IV undergo a repeat PET2 at time of PSA progression or clinical concerns for progression or 12 months after completion of enhanced systemic therapy, whichever occurs first. Patients in Arm C or D using another tracer for PET1 do not undergo PET2. STEP 1: Patients who are PET negative for extera pelvic metastases undergo SOC EBRT for 6 months. Patients also receive goserelin acetate SC, leuprolide acetate IM, triptorelin IM, relugolix PO, or degarelix SC for 6 months starting up to 3 months prior to EBRT but no later than 7 days after start of EBRT. All treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.

    Procedure: Computed Tomography · Drug: Degarelix · Radiation: External Beam Radiation Therapy · Other: Fluciclovine F18 · Drug: Goserelin Acetate · Drug: Leuprolide Acetate · Procedure: Magnetic Resonance Imaging · Procedure: Positron Emission Tomography · Other: Quality-of-Life Assessment · Other: Questionnaire Administration · Drug: Relugolix · Drug: Triptorelin

  • Experimental
    Arm B (EBRT, STAD, apalutamide)

    STEP 0: Patients undergo SOC PET/CT or PET/MR scan at baseline. Patients randomized to Arms C or D and receiving fluciclovine F18 IV undergo a repeat PET2 at time of PSA progression or clinical concerns for progression or 12 months after completion of enhanced systemic therapy, whichever occurs first. Patients in Arm C or D using another tracer for PET1 do not undergo PET2. STEP 1: Patients who are PET negative for extra pelvic metastases undergo SOC EBRT and receive goserelin acetate SC, leuprolide acetate IM, triptorelin IM, relugolix PO, or degarelix SC as in Arm A. Patients also receive apalutamide PO QD for 6 months in the absence of disease progression or unacceptable toxicity.

    Drug: Apalutamide · Procedure: Computed Tomography · Drug: Degarelix · Radiation: External Beam Radiation Therapy · Other: Fluciclovine F18 · Drug: Goserelin Acetate · Drug: Leuprolide Acetate · Procedure: Magnetic Resonance Imaging · Procedure: Positron Emission Tomography · Other: Quality-of-Life Assessment · Other: Questionnaire Administration · Drug: Relugolix · Drug: Triptorelin

  • Experimental
    Arm C (EBRT, STAD, apalutamide)

    STEP 0: Patients undergo SOC PET/CT or PET/MR scan at baseline. Patients randomized to Arms C or D and receiving fluciclovine F18 IV undergo a repeat PET2 at time of PSA progression or clinical concerns for progression or 12 months after completion of enhanced systemic therapy, whichever occurs first. Patients in Arm C or D using another tracer for PET1 do not undergo PET2. STEP 1: Patients who are PET positive for extra pelvic metastases undergo SOC EBRT and receive goserelin acetate SC, leuprolide acetate IM, triptorelin IM, relugolix PO, or degarelix SC as in Arm A. Patients also receive apalutamide PO QD as in Arm B.

    Drug: Apalutamide · Procedure: Computed Tomography · Drug: Degarelix · Radiation: External Beam Radiation Therapy · Other: Fluciclovine F18 · Drug: Goserelin Acetate · Drug: Leuprolide Acetate · Procedure: Magnetic Resonance Imaging · Procedure: Positron Emission Tomography · Other: Quality-of-Life Assessment · Other: Questionnaire Administration · Drug: Relugolix · Drug: Triptorelin

  • Experimental
    Arm D (EBRT, STAD, apalutamide, RT)

    STEP 0: Patients undergo SOC PET/CT or PET/MR scan at baseline. Patients randomized to Arms C or D and receiving fluciclovine F18 IV undergo a repeat PET2 at time of PSA progression or clinical concerns for progression or 12 months after completion of enhanced systemic therapy, whichever occurs first. Patients in Arm C or D using another tracer for PET1 do not undergo PET2. STEP 1: Patients who are PET positive for extra pelvic metastases undergo SOC EBRT and receive goserelin acetate SC, leuprolide acetate IM, triptorelin IM, relugolix PO, or degarelix SC as in Arm A and apalutamide PO QD as in Arm B. Patients also undergo SBRT or 3D CRT, IMRT (including VMAT), and IMPT over 3-10 fractions in the absence of disease progression or unacceptable toxicity.

    Radiation: 3-Dimensional Conformal Radiation Therapy · Drug: Apalutamide · Procedure: Computed Tomography · Drug: Degarelix · Radiation: External Beam Radiation Therapy · Other: Fluciclovine F18 · Drug: Goserelin Acetate · Procedure: Intensity-Modulated Proton Therapy · Radiation: Intensity-Modulated Radiation Therapy · Drug: Leuprolide Acetate · Procedure: Magnetic Resonance Imaging · Procedure: Positron Emission Tomography · Other: Quality-of-Life Assessment · Other: Questionnaire Administration · Drug: Relugolix · Radiation: Stereotactic Body Radiation Therapy · Drug: Triptorelin · Radiation: Volume Modulated Arc Therapy

Interventions

  • Radiation3-Dimensional Conformal Radiation Therapy

    Undergo 3D CRT

    Also known as: 3-dimensional radiation therapy, 3D Conformal, 3D CONFORMAL RADIATION THERAPY, 3D CRT, 3D radiotherapy, 3D-CRT, Conformal Therapy, Radiation Conformal Therapy, Radiation, 3D Conformal, Three dimensional external beam radiation therapy (procedure)

  • DrugApalutamide

    Given PO

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

  • ProcedureComputed Tomography

    Undergo PET/CT

    Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

  • DrugDegarelix

    Given SC

    Also known as: FE200486, Firmagon

  • RadiationExternal Beam Radiation Therapy

    Undergo EBRT

    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

  • OtherFluciclovine F18

    Given IV

    Also known as: (18F)Fluciclovine, (18F)GE-148, 18F-Fluciclovine, [18F]FACBC, Anti-(18f)FABC, Anti-1-Amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid, Anti-[18F] FACBC, Axumin, Fluciclovine (18F), FLUCICLOVINE F-18, GE-148 (18F), GE-148 F-18

  • DrugGoserelin Acetate

    Given SC

    Also known as: ZDX, Zoladex

  • ProcedureIntensity-Modulated Proton Therapy

    Undergo IMPT

    Also known as: IMPT

  • RadiationIntensity-Modulated Radiation Therapy

    Undergo IMRT

    Also known as: IMRT, Intensity modulated radiation therapy (procedure), Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy

  • DrugLeuprolide Acetate

    Given IM

    Also known as: A-43818, Abbott 43818, Abbott-43818, Carcinil, Depo-Eligard, Eligard, Enanton, Enantone, Enantone-Gyn, Ginecrin, LEUP, Leuplin, Leuprorelin Acetate, Lucrin, Lucrin Depot, Lupron, Lupron Depot, Lupron Depot-3 Month, Lupron Depot-4 Month, Lupron Depot-Ped, Lutrate, Procren, Procrin, Prostap, TAP-144, Trenantone, Uno-Enantone, Viadur

  • ProcedureMagnetic Resonance Imaging

    Undergo PET/MR

    Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

  • ProcedurePositron Emission Tomography

    Undergo PET/CT or PET/MR

    Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

  • OtherQuality-of-Life Assessment

    Ancillary studies

    Also known as: Quality of Life Assessment

  • OtherQuestionnaire Administration

    Ancillary studies

  • DrugRelugolix

    Given PO

    Also known as: N-(4-(1-((2,6-Difluorophenyl)methyl)-5-((dimethylamino)methyl)-1,2,3,4-tetrahydro-3-(6-methoxy-3-pyridazinyl)-2,4-dioxothieno(2,3-d)pyrimidin-6-yl)phenyl)-N'-methoxyurea, Orgovyx, TAK 385, TAK-385

  • RadiationStereotactic Body Radiation Therapy

    Undergo SBRT

    Also known as: SABR, SBRT, Stereotactic Ablative Body Radiation Therapy

  • DrugTriptorelin

    Given IM

    Also known as: 6-D-Tryptophan-LH-RH, 6-D-Tryptophanluteinizing Hormone-releasing Factor, AY-25650, CL-118,532, Detryptoreline

  • RadiationVolume Modulated Arc Therapy

    Undergo VMAT

    Also known as: VMAT, Volumetric Modulated Arc Therapy (procedure)

06

What researchers measure

Primary outcomes

  1. Progression-free survival (PFS)

    The power of the PFS analysis is 85% using one-sided 0.025 level stratified logrank test. The overall type I error will be controlled using an O'Brien-Fleming boundary function

    Time frame: From randomization to radiographic progression by conventional imaging or positron emission tomography (PET), symptomatic disease or death, whichever occurs first, assessed up to 10 years

  2. PFS prolongation in patients without PET-evidence of extrapelvic metastases

    Will evaluate whether the addition of enhanced systemic therapy to standard of care salvage therapy could prolong PFS in this patient population. Will be an intention-to-treat analysis of all randomized patients and performed in parallel with patients with PET-evidence of extrapelvic metastases.

    Time frame: Up to 10 years

  3. PFS prolongation in patients with PET-evidence of extrapelvic metastases

    Will evaluate whether the addition of metastasis-directed radiation therapy to standard of care salvage therapy and enhanced systemic therapy could prolong PFS in this patient population. Will be an intention-to-treat analysis of all randomized patients and performed in parallel without patients with PET-evidence of extrapelvic metastases.

    Time frame: Up to 10 years

  4. Quality of life (QOL)

    Descriptive statistics will be used to characterize QOL over time in each arm.

    Time frame: Up to 24 months

Secondary outcomes

  1. Overall survival (OS)

    Will be characterized by the method of Kaplan and Meier and a logrank test will be used to compare OS between the two arms in each cohort.

    Time frame: From randomization to death or date last known alive, assessed up to 10 years

  2. Event-free survival

    Will be characterized by the method of Kaplan and Meier and a logrank test will be used to compare EFS between the two arms in each cohort.

    Time frame: From randomization to radiographic progression by conventional imaging or PET, symptomatic disease, or initiation of new treatment for the disease or death, whichever occurs first, assessed up to 10 years

  3. Time to prostate-specific antigen (PSA) progression

    Patients without any progression will be censored at the date of last disease assessment that shows free of PSA progression. Will be characterized by the method of Kaplan and Meier and a logrank test will be used to compare time to PSA progression between the two arms in each cohort.

    Time frame: From randomization to documented PSA progression or radiographic progression, whichever occurs first, assessed up to 10 years

  4. Incidence of adverse events

    Toxicity will be defined using the Common Terminology Criteria for Adverse Events.

    Time frame: Up to 10 years

  5. Detection rate of fluciclovine F18 (18F-fluciclovine) PET

    For the detection rate, the proportion of baseline standard of care 18F-fluciclovine PET (PET1) positive results at the patient and regional (prostate fossa, intrapelvic soft tissue/lymph node, extrapelvic soft tissue/lymph node, and bone metastases) level will be calculated and its 95% confidence interval will be estimated using the Exact method based on the binomial distribution.

    Time frame: At time of PSA recurrence, as clinically indicated or 12 months after completion of enhanced systemic therapy (whichever occurs first), assessed up to 10 years

  6. Concordance of detection rate with the follow-up conventional imaging modalities (CIM)

    Will use Cohen's Kappa coefficient to measure the agreement between dichotomized PET results and the dichotomized CIM results. Baseline CIM comparison will not be performed because as per our study eligibility criteria, baseline CIM will be negative for metastases.

    Time frame: At time of PSA recurrence, as clinically indicated or 12 months after completion of enhanced systemic therapy (whichever occurs first), assessed up to 10 years

  7. Distribution of 18F-fluciclovine PET-positive lesions among anatomic sites

    The rate of 18F-fluciclovine PET-positive lesions will be reported for each anatomic site, including prostate fossa, intrapelvic soft tissue/lymph node, extrapelvic soft tissue/lymph node, and bone metastases. Their confidence intervals will be estimated using the Exact method for the binomial distribution. To evaluate if PSA (level, doubling time, velocity) and other relevant clinical parameters affects the positivity distribution, will use the logistic regression to model with the binary outcome (positive vs. negative from PET) and covariates will include anatomic site, PSA, and other clinical parameters. Will test the interactions between anatomic site and PSA (plus other clinical parameters) to see if the positivity distribution across anatomic site may change according to the levels of the interacted terms. Will use the technique of generalized estimating equation to account for the outcome correlations within subjects.

    Time frame: Baseline

  8. Value of repeat PET to assess response to therapy compared to standard response assessments

    Analyses will be conducted to evaluate qualitative visual evidence of 18F-fluciclovine PET positive metastatic lesions and quantitative PET standardized-uptake value (SUV) changes on a lesion-to-lesion basis from 18F-fluciclovine PET1 (baseline) to PET2 on visually determined sites of recurrence and metastatic disease. This will be compared to reference standard-of-care conventional imaging (Prostate Cancer Working Group 2 criteria) and PSA response at PET2 time point to determine PET2 response to therapy. PET2 visual and quantitative assessment will also be compared to PFS in the time-to-event analysis using a log-rank test (PET2 visual assessment) and a Cox proportional hazards regression (PET2 quantitative assessment). PET SUV parameters to be obtained at PET1 and PET2 will include SUVmax, SUVpeak. PET SUV change from PET1 to PET2 will include absolute SUVmax and SUVpeak change (PET2-PET1) and percent change of SUVmax and SUVpeak (% change = 100\*\[(PET2-PET1)/PET1\]).)

    Time frame: At time of second PSA recurrence or 12 months after completion of enhanced systemic therapy (whichever occurs first), assessed up to 10 years

  9. Comparison - Functional Assessment of Cancer Therapy (FACT)- prostate (P)

    For the PET-negative cohort, with 216 analyzable patients in each arm, the study will have about 84% power to detect a 6-point (0.29 standard deviation) difference between the two arms using a two-sample t test with two-sided type I error of 0.05. The power will be greater than 99% if the difference between the two arms is 10 points (0.48 standard deviation). For the PET-positive cohort, with 146 analyzable patients in each arm, the study will have 68% and 98% power to detect a 6-point (0.29 standard deviation) and a 10-point (0.48 standard deviation) differences between the two arms, respectively, using the same test.

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

  10. Change in FACT-P and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue

    A paired t test will be used to compare FACT-P scores at these two time points in each arm. A two-sample t test will be performed to compare the changes in FACT-P scores from baseline to 6 months between the two arms of each cohort. The FACIT-Fatigue scores at 6 months will be compared between the two arms of each cohort using a two-sample t test.

    Time frame: Baseline up to 6 months

  11. QOL Assessments at Progression

    A paired t test will be used to compare FACT-P total scores, FACIT-Fatigue scores and pain scores at these two time points in each arm. The changes in these scores from baseline to progression will be evaluated in each arm.

    Time frame: Up to 10 years

  12. FACT- cognitive functioning (Cog)

    Will be compared between two groups of patients on this study, patients receiving antiandrogen therapy (ADT) + apalutamide (Arms B, C and D) and patients receiving ADT alone (Arm A), at different time points. To ensure similarity of the three arms with systemic treatments (Arms B, C and D), a comparison in FACT-Cog total scores among these three arms will be performed using the Kruskal-Wallis test before combining them together to be compared with Arm A.

    Time frame: Up to 12 months

07

Study locations

278 of 341 sites recruiting
  • Anchorage Associates in Radiation Medicine
    Anchorage, Alaska 98508, United States
    Recruiting
  • Alaska Breast Care and Surgery LLC
    Anchorage, Alaska 99508, United States
    Recruiting
  • Alaska Oncology and Hematology LLC
    Anchorage, Alaska 99508, United States
    Recruiting
  • Alaska Women's Cancer Care
    Anchorage, Alaska 99508, United States
    Recruiting
  • Anchorage Oncology Centre
    Anchorage, Alaska 99508, United States
    Suspended
  • Katmai Oncology Group
    Anchorage, Alaska 99508, United States
    Recruiting
  • Providence Alaska Medical Center
    Anchorage, Alaska 99508, United States
    Recruiting
  • Fairbanks Memorial Hospital
    Fairbanks, Alaska 99701, United States
    Recruiting
  • Cancer Center at Saint Joseph's
    Phoenix, Arizona 85004, United States
    Recruiting
  • Mercy Hospital Fort Smith
    Fort Smith, Arkansas 72903, United States
    • Site Public Contact · Contact · 800-378-9373
    • Jay W. Carlson · Principal investigator
    Recruiting
  • Mission Hope Medical Oncology - Arroyo Grande
    Arroyo Grande, California 93420, United States
    Recruiting
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    Burbank, California 91505, United States
    Recruiting
  • Mercy Cancer Center - Carmichael
    Carmichael, California 95608, United States
    Recruiting
  • Mercy San Juan Medical Center
    Carmichael, California 95608, United States
    Recruiting
  • City of Hope Corona
    Corona, California 92882, United States
    Recruiting
  • City of Hope Comprehensive Cancer Center
    Duarte, California 91010, United States
    • Scott M. Glaser · Contact · sglaser@coh.org · 626-218-2247
    • Scott M. Glaser · Principal investigator
    Recruiting
  • Mercy Cancer Center - Elk Grove
    Elk Grove, California 95758, United States
    Recruiting
  • UC San Diego Health System - Encinitas
    Encinitas, California 92024, United States
    • Site Public Contact · Contact · 760-536-7700
    • James M. Randall · Principal investigator
    Recruiting
  • UC San Diego Moores Cancer Center
    La Jolla, California 92093, United States
    • Site Public Contact · Contact · cancercto@ucsd.edu · 858-822-5354
    • James M. Randall · Principal investigator
    Recruiting
  • City of Hope Antelope Valley
    Lancaster, California 93534, United States
    Recruiting
  • Los Angeles General Medical Center
    Los Angeles, California 90033, United States
    Active, not recruiting
  • USC / Norris Comprehensive Cancer Center
    Los Angeles, California 90033, United States
    Active, not recruiting
  • UCLA / Jonsson Comprehensive Cancer Center
    Los Angeles, California 90095, United States
    • Site Public Contact · Contact · 888-798-0719
    • Amar Kishan · Principal investigator
    Recruiting
  • Mercy Cancer Center
    Merced, California 95340, United States
    Suspended
  • VA Palo Alto Health Care System
    Palo Alto, California 94304, United States
    Active, not recruiting
  • Mercy Cancer Center - Rocklin
    Rocklin, California 95765, United States
    Recruiting
  • Mercy Cancer Center - Sacramento
    Sacramento, California 95816, United States
    Recruiting
  • UC San Diego Medical Center - Hillcrest
    San Diego, California 92103, United States
    Recruiting
  • Pacific Central Coast Health Center-San Luis Obispo
    San Luis Obispo, California 93401, United States
    Recruiting
  • Mission Hope Medical Oncology - Santa Maria
    Santa Maria, California 93444, United States
    Recruiting
  • City of Hope South Pasadena
    South Pasadena, California 91030, United States
    Recruiting
  • Saint Joseph's Medical Center
    Stockton, California 95204, United States
    • Site Public Contact · Contact · 209-461-5257
    • Shahzad Siddique · Principal investigator
    Recruiting
  • City of Hope Upland
    Upland, California 91786, United States
    Recruiting
  • BASS Medical Group - Lennon
    Walnut Creek, California 94598, United States
    Active, not recruiting
  • Woodland Memorial Hospital
    Woodland, California 95695, United States
    Recruiting
  • Rocky Mountain Cancer Centers-Aurora
    Aurora, Colorado 80012, United States
    Active, not recruiting
  • Rocky Mountain Cancer Centers-Boulder
    Boulder, Colorado 80304, United States
    Active, not recruiting
  • Penrose-Saint Francis Healthcare
    Colorado Springs, Colorado 80907, United States
    Recruiting
  • Rocky Mountain Cancer Centers-Penrose
    Colorado Springs, Colorado 80907, United States
    Recruiting
  • Saint Francis Cancer Center
    Colorado Springs, Colorado 80923, United States
    Recruiting
  • AdventHealth Porter
    Denver, Colorado 80210, United States
    Suspended
  • Presbyterian - Saint Lukes Medical Center - Health One
    Denver, Colorado 80218, United States
    Active, not recruiting
  • Dillon Health Center/Shaw Cancer Center
    Dillon, Colorado 80435, United States
    • Site Public Contact · Contact · 970-470-7170
    • Erin Schwab · Principal investigator
    Recruiting
  • Shaw Cancer Center
    Edwards, Colorado 81632, United States
    • Site Public Contact · Contact · 970-569-7429
    • Erin Schwab · Principal investigator
    Recruiting
  • The Melanoma and Skin Cancer Institute
    Englewood, Colorado 80113, United States
    Active, not recruiting
  • CommonSpirit Saint Anthony Hospital Cancer Center
    Lakewood, Colorado 80228, United States
    Recruiting
  • Rocky Mountain Cancer Centers-Littleton
    Littleton, Colorado 80120, United States
    Active, not recruiting
  • AdventHealth Littleton
    Littleton, Colorado 80122, United States
    Suspended
  • Longmont United Hospital
    Longmont, Colorado 80501, United States
    Recruiting
  • AdventHealth Parker
    Parker, Colorado 80138, United States
    Suspended
  • Saint Mary Corwin Medical Center
    Pueblo, Colorado 81004, United States
    Recruiting
  • Rocky Mountain Cancer Centers-Thornton
    Thornton, Colorado 80260, United States
    Active, not recruiting
  • Saint Anthony North Hospital
    Westminster, Colorado 80023, United States
    Recruiting
  • Sibley Memorial Hospital
    Washington D.C., District of Columbia 20016, United States
    • Site Public Contact · Contact · jquiver1@jhmi.edu · 202-243-2373
    • Curtiland Deville · Principal investigator
    Recruiting
  • Moffitt Cancer Center-International Plaza
    Tampa, Florida 33607, United States
    Recruiting
  • Moffitt Cancer Center - McKinley Campus
    Tampa, Florida 33612, United States
    Recruiting
  • Moffitt Cancer Center
    Tampa, Florida 33612, United States
    Recruiting
  • Moffitt Cancer Center at Wesley Chapel
    Wesley Chapel, Florida 33544, United States
    Recruiting
  • Saint Alphonsus Cancer Care Center-Boise
    Boise, Idaho 83706, United States
    Suspended
  • Saint Luke's Cancer Institute - Boise
    Boise, Idaho 83712, United States
    • Site Public Contact · Contact · eslinget@slhs.org · 208-381-2774
    • Alison K. Conlin · Principal investigator
    Recruiting
  • Saint Alphonsus Cancer Care Center-Caldwell
    Caldwell, Idaho 83605, United States
    Suspended
  • Kootenai Health - Coeur d'Alene
    Coeur d'Alene, Idaho 83814, United States
    • Site Public Contact · Contact · mccinfo@mtcancer.org · 406-969-6060
    • John M. Schallenkamp · Principal investigator
    Recruiting
  • Saint Luke's Cancer Institute - Fruitland
    Fruitland, Idaho 83619, United States
    • Site Public Contact · Contact · eslinget@slhs.org · 208-381-2774
    • Alison K. Conlin · Principal investigator
    Recruiting
  • Idaho Urologic Institute-Meridian
    Meridian, Idaho 83642, United States
    Suspended
  • Saint Luke's Cancer Institute - Meridian
    Meridian, Idaho 83642, United States
    • Site Public Contact · Contact · eslinget@slhs.org · 208-381-2774
    • Alison K. Conlin · Principal investigator
    Recruiting
  • Saint Alphonsus Cancer Care Center-Nampa
    Nampa, Idaho 83687, United States
    Suspended
  • Saint Luke's Cancer Institute - Nampa
    Nampa, Idaho 83687, United States
    • Site Public Contact · Contact · eslinget@slhs.org · 208-381-2774
    • Alison K. Conlin · Principal investigator
    Recruiting
  • Kootenai Clinic Cancer Services - Post Falls
    Post Falls, Idaho 83854, United States
    • Site Public Contact · Contact · mccinfo@mtcancer.org · 406-969-6060
    • John M. Schallenkamp · Principal investigator
    Recruiting
  • Saint Luke's Cancer Institute - Twin Falls
    Twin Falls, Idaho 83301, United States
    • Site Public Contact · Contact · eslinget@slhs.org · 208-381-2774
    • Alison K. Conlin · Principal investigator
    Recruiting
  • Alton Memorial Hospital
    Alton, Illinois 62002, United States
    • Site Public Contact · Contact · 618-463-7323
    • Jeff M. Michalski · Principal investigator
    Recruiting
  • OSF Saint Anthony's Health Center
    Alton, Illinois 62002, United States
    • Site Public Contact · Contact · 618-463-5623
    • Jay W. Carlson · Principal investigator
    Recruiting
  • Rush-Copley Medical Center
    Aurora, Illinois 60504, United States
    Recruiting
  • Illinois CancerCare-Bloomington
    Bloomington, Illinois 61704, United States
    Recruiting
  • Illinois CancerCare-Canton
    Canton, Illinois 61520, United States
    Recruiting
  • Memorial Hospital of Carbondale
    Carbondale, Illinois 62902, United States
    Recruiting
  • SIH Cancer Institute
    Carterville, Illinois 62918, United States
    Recruiting
  • Illinois CancerCare-Carthage
    Carthage, Illinois 62321, United States
    Recruiting
  • Centralia Oncology Clinic
    Centralia, Illinois 62801, United States
    Recruiting
  • Saint Mary's Hospital
    Centralia, Illinois 62801, United States
    Suspended
  • Northwestern University
    Chicago, Illinois 60611, United States
    Recruiting
  • Rush MD Anderson Cancer Center
    Chicago, Illinois 60612, United States
    Recruiting
  • University of Illinois
    Chicago, Illinois 60612, United States
    • Site Public Contact · Contact · 312-355-3046
    • Daniel Moreira · Principal investigator
    Recruiting
  • Carle at The Riverfront
    Danville, Illinois 61832, United States
    • Site Public Contact · Contact · Research@Carle.com · 800-446-5532
    • Sinisa Stanic · Principal investigator
    Recruiting
  • Cancer Care Specialists of Illinois - Decatur
    Decatur, Illinois 62526, United States
    Recruiting
  • Decatur Memorial Hospital
    Decatur, Illinois 62526, United States
    Recruiting
  • Northwestern Medicine Cancer Center Kishwaukee
    DeKalb, Illinois 60115, United States
    • Site Public Contact · Contact · Donald.Smith3@nm.org · 630-352-5360
    • William F. Hartsell · Principal investigator
    Recruiting
  • Illinois CancerCare-Dixon
    Dixon, Illinois 61021, United States
    Suspended
  • Carle Physician Group-Effingham
    Effingham, Illinois 62401, United States
    • Site Public Contact · Contact · Research@carle.com · 800-446-5532
    • Sinisa Stanic · Principal investigator
    Recruiting
  • Crossroads Cancer Center
    Effingham, Illinois 62401, United States
    Recruiting
  • Illinois CancerCare-Eureka
    Eureka, Illinois 61530, United States
    Recruiting
  • Illinois CancerCare-Galesburg
    Galesburg, Illinois 61401, United States
    Recruiting
  • Western Illinois Cancer Treatment Center
    Galesburg, Illinois 61401, United States
    Suspended
  • Northwestern Medicine Cancer Center Delnor
    Geneva, Illinois 60134, United States
    • Site Public Contact · Contact · Donald.Smith3@nm.org · 630-352-5360
    • William F. Hartsell · Principal investigator
    Recruiting
  • Illinois CancerCare-Kewanee Clinic
    Kewanee, Illinois 61443, United States
    Recruiting
  • Rush MD Anderson Cancer Center at Rush Lisle
    Lisle, Illinois 60532, United States
    Recruiting
  • Illinois CancerCare-Macomb
    Macomb, Illinois 61455, United States
    Recruiting
  • Carle Physician Group-Mattoon/Charleston
    Mattoon, Illinois 61938, United States
    • Site Public Contact · Contact · Research@carle.com · 800-446-5532
    • Sinisa Stanic · Principal investigator
    Recruiting
  • Loyola University Medical Center
    Maywood, Illinois 60153, United States
    Active, not recruiting
  • SSM Health Good Samaritan
    Mount Vernon, Illinois 62864, United States
    Recruiting
  • Cancer Care Center of O'Fallon
    O'Fallon, Illinois 62269, United States
    Recruiting

Showing the first 100 of 341 sites.

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 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 ↗
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 19, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04423211
Lead sponsor
ECOG-ACRIN Cancer Research Group
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Jun 9, 2020
Start date
Oct 8, 2020
Primary completion
Dec 31, 2032 (estimated)
Completion
Dec 31, 2032 (estimated)
Last update
Aug 19, 2026

Study contacts

Neha Vapiwala
principal investigator · ECOG-ACRIN Cancer Research Group

Oversight

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

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