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Two Studies for Patients With High Risk Prostate Cancer Testing Less Intense Treatment for Patients With a Low Gene Risk Score and Testing a More Intense Treatment for Patients With a High Gene Risk Score, The PREDICT-RT Trial

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04513717
Recruitment Status : Suspended (Design change)
First Posted : August 14, 2020
Last Update Posted : September 28, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NRG Oncology

Tracking Information
First Submitted Date  ICMJE August 7, 2020
First Posted Date  ICMJE August 14, 2020
Last Update Posted Date September 28, 2021
Actual Study Start Date  ICMJE December 15, 2020
Estimated Primary Completion Date December 31, 2033   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 11, 2020)
Metastasis-Free Survival (MFS) [ Time Frame: From randomization to the date of detection of distant metastasis on standard imaging or date of death from any cause, assessed up to 13 years ]
Assessed based on conventional imaging. MFS will be estimated using the Kaplan-Meier method (Kaplan 1958).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 13, 2020)
  • Overall Survival (OS) [ Time Frame: From the date of randomization to the date of death or last known follow-up date, with patients alive at the last known follow-up time treated as censored, assessed up to 13 years ]
    Will be estimated using the Kaplan-Meier method and treatment arms compared using the stratified log-rank test (Kaplan 1958).
  • Prostate Specific Antigen (PSA) failure-free survival with non-castrate testosterone and no additional therapies [ Time Frame: From the date of randomization to the date event, or death or censored at the last known follow-up date, assessed up to 13 years ]
    PSA failure-free survival will be estimated using the Kaplan-Meier method and treatment arms compared using the stratified log-rank test (Kaplan 1958).
  • Prostate Cancer Specific Mortality (PCSM) [ Time Frame: From the date of randomization to the date of prostate cancer death, assessed up to 13 years ]
  • Time to testosterone recovery [ Time Frame: Up to 13 years ]
    Defined as testosterone that is non-castrate.
  • Time to PSA failure or salvage therapy [ Time Frame: Up to 13 years ]
  • Testosterone levels at the time of PSA failure and metastases [ Time Frame: Up to 13 years ]
  • Incidence of Adverse Events [ Time Frame: Up to 13 years ]
    Measured by the Common Terminology Criteria for Adverse Events (CTCAE ) version (v) 5.0 and Patient Reported Outcomes (PRO)-CTCAE.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 11, 2020)
  • MFS [ Time Frame: From randomization to the date of detection of distant metastasis on standard imaging or date of death from any cause, assessed up to 13 years ]
    Assessed based on standard or molecular, if available, imaging. MFS will be estimated using the Kaplan-Meier method (Kaplan 1958)
  • Overall Survival [ Time Frame: From the date of randomization to the date of death or last known follow-up date, with patients alive at the last known follow-up time treated as censored, assessed up to 13 years ]
    Will be estimated using the Kaplan-Meier method and treatment arms compared using the stratified log-rank test (Kaplan 1958).
  • Prostate Cancer Specific Mortality (PCSM) [ Time Frame: From the date of randomization to the date of prostate cancer death, assessed up to 13 years ]
  • Prostate Specific Antigen (PSA) failure-free survival with non-castrate testosterone and no additional therapies [ Time Frame: From the date of randomization to the date event, or death or censored at the last known follow-up date, assessed up to 13 years ]
    PSA failure-free survival will be estimated using the Kaplan-Meier method and treatment arms compared using the stratified log-rank test (Kaplan 1958).
  • Time to testosterone recovery [ Time Frame: Up to 13 years ]
    Defined as testosterone that is non-castrate.
  • Time to PSA failure or salvage therapy [ Time Frame: Up to 13 years ]
  • Testosterone levels at the time of PSA failure and metastases [ Time Frame: Up to 13 years ]
  • Incidence of Adverse Events [ Time Frame: Up to 13 years ]
    Measured by the Common Terminology Criteria for Adverse Events (CTCAE ) version (v) 5.0 and Patient Reported Outcomes (PRO)-CTCAE.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Two Studies for Patients With High Risk Prostate Cancer Testing Less Intense Treatment for Patients With a Low Gene Risk Score and Testing a More Intense Treatment for Patients With a High Gene Risk Score, The PREDICT-RT Trial
Official Title  ICMJE Parallel Phase III Randomized Trials for High Risk Prostate Cancer Evaluating De-Intensification for Lower Genomic Risk and Intensification of Concurrent Therapy for Higher Genomic Risk With Radiation (PREDICT-RT*)
Brief Summary This phase III trial compares less intense hormone therapy and radiation therapy to usual hormone therapy and radiation therapy in treating patients with high risk prostate cancer and low gene risk score. This trial also compares more intense hormone therapy and radiation therapy to usual hormone therapy and radiation therapy in patients with high risk prostate cancer and high gene risk score. Abiraterone acetate may help fight prostate cancer by lowering the amount of testosterone made by the body. Apalutamide may help fight prostate cancer by blocking the use of androgen by the tumor cells. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Giving a shorter hormone therapy treatment may work the same at controlling prostate cancer compared to the usual 24 month hormone therapy treatment in patients with low gene risk score. Adding abiraterone acetate and apalutamide to the usual treatment may increase the length of time without prostate cancer spreading as compared to the usual treatment in patients with high gene risk score.
Detailed Description

PRIMARY OBJECTIVES:

I. To determine whether men with National Comprehensive Cancer Network (NCCN) high risk prostate cancer who are in the lower 2/3 of Decipher genomic risk (=< 0.8) can be treated with 12 months androgen deprivation therapy (ADT) plus radiation therapy (RT) instead of 24 months ADT+RT and experience non-inferior metastasis-free survival. (De-intensification study) II. To determine whether men with NCCN high risk prostate cancer who are in the upper 1/3 of Decipher genomic risk (> 0.8) or have node-positive disease by conventional imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan) will have a superior metastasis-free survival (MFS) through treatment intensification with apalutamide and abiraterone acetate with prednisone added to the standard of RT plus 24 month ADT. (Intensification study)

SECONDARY OBJECTIVES:

I. To compare overall survival (OS) between the standard of care (RT plus 24 months of ADT) and either the de intensification (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide and abiraterone acetate with prednisone). (De-intensification and intensification studies) II. To compare time to prostate specific antigen (PSA) failure or start of salvage treatment between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide and abiraterone acetate with prednisone). (De-intensification and intensification studies) III. To compare PSA failure-free survival with non-castrate testosterone and no additional therapies between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide and abiraterone acetate with prednisone). (De-intensification and intensification studies) IV. To compare MFS judged based on either standard or molecular imaging between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide and abiraterone acetate with prednisone). (De-intensification and intensification studies) V. To compare prostate cancer-specific mortality between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide and abiraterone acetate with prednisone). (De-intensification and intensification studies) VI. To compare testosterone levels at the time of PSA failure and metastases between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide and abiraterone acetate with prednisone). (De-intensification and intensification studies) VII. To compare time to testosterone recovery (defined as a T > 200) between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide and abiraterone acetate with prednisone). (De-intensification and intensification studies) VIII. To compare adverse events, both clinician-reported using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 and patient-reported using patient reported outcome (PRO)-CTCAE items, between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide and abiraterone acetate with prednisone). (De-intensification and intensification studies)

CORRELATIVE STUDIES OBJECTIVE:

I. To compare extra-prostatic uptake on the positron emission tomography (PET)-CT between the standard of care (RT plus 24 months of ADT) and intensification arm (RT plus 24 months of ADT plus apalutamide and abiraterone acetate with prednisone). (Intensification study)

EXPLORATORY OBJECTIVES:

I. To compare changes in cardio-metabolic markers, including body mass index, and waist circumference, between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide and abiraterone acetate with prednisone). (De-intensification and intensification studies) II. To determine a machine learning/artificial intelligence algorithm for radiotherapy quality assurance. (De-intensification and Intensification studies) III. To perform future translational correlative studies using biological and imaging data. (De-intensification and intensification studies)

OUTLINE: Patients are randomized to 1 of 4 arms.

DE-INTENSIFICATION STUDY (DECIPHER SCORE =< 0.8):

ARM I: Patients undergo radiation therapy (RT) over 4-9 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin or histrelin and bicalutamide or flutamide) for 24 months in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo RT over 4-9 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin or histrelin and bicalutamide or flutamide) for 12 months in the absence of disease progression or unacceptable toxicity.

INTENSIFICATION STUDY (DECIPHER SCORE > 0.8 OR NODE POSITIVE):

ARM III: Patients undergo RT over 4-9 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin or histrelin and bicalutamide or flutamide) for 24 months in the absence of disease progression or unacceptable toxicity.

ARM IV: Patients undergo RT over 4-9 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin or histrelin) for 24 months in the absence of disease progression or unacceptable toxicity. Patients also receive apalutamide, abiraterone acetate and prednisone orally (PO) once daily (QD). Treatment repeats every 90 days for up to 8 cycles (24 months) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up annually.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Malignant Neoplasm in the Bone
  • Prostate Adenocarcinoma
  • Stage III Prostate Cancer AJCC v8
  • Stage IIIA Prostate Cancer AJCC v8
  • Stage IIIB Prostate Cancer AJCC v8
  • Stage IIIC Prostate Cancer AJCC v8
  • Stage IVA Prostate Cancer AJCC v8
Intervention  ICMJE
  • Drug: Abiraterone Acetate
    Given PO
    Other Names:
    • CB7630
    • Yonsa
    • Zytiga
  • Drug: Apalutamide
    Given PO
    Other Names:
    • ARN 509
    • ARN-509
    • ARN509
    • Erleada
    • JNJ 56021927
    • JNJ-56021927
  • Drug: Bicalutamide
    Hormone therapy. Given PO
    Other Names:
    • Casodex
    • Cosudex
    • ICI 176,334
    • ICI 176334
  • Drug: Buserelin
    Hormone therapy. Given by injection.
    Other Names:
    • 6-[O-(1,1-Dimethylethyl)-D-serine]-9-(N-ethyl-L-prolinamide)-10-deglycinamide-luteinizing Hormone-releasing Factor (Pig)
    • BSRL
    • Busereline
    • Etilamide
    • HOE 766
    • ICI 123215
    • S74-6766
  • Drug: Degarelix
    Hormone therapy. Given by injection.
    Other Names:
    • FE200486
    • Firmagon
  • Drug: Flutamide
    Anti-androgen
    Other Names:
    • 4''-Nitro-3''-trifluoromethylisobutyranilide
    • Apimid
    • Cebatrol
    • Chimax
    • Cytomid
    • Drogenil
    • Euflex
    • Eulexine
    • Flucinom
    • Flucinome
    • Flugerel
    • Fluken
    • Flulem
    • FLUT
    • Fluta-Gry
    • Flutabene
    • Flutacan
    • Flutamex
    • Flutamin
    • Flutan
    • Flutaplex
    • Fugerel
    • Grisetin
    • Niftolide
    • Oncosal
    • Profamid
    • Propanamide, 2-Methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)-
    • Prostacur
    • Prostadirex
    • Prostica
    • Prostogenat
    • Sch 13521
    • Tafenil
    • Tecnoflut
    • Testotard
  • Drug: Goserelin
    Anti-androgen
    Other Name: ICI-118630
  • Drug: Histrelin
    Anti-gonadotropin
  • Drug: Leuprolide
    Hormone therapy.
    Other Name: Leuprorelin
  • Drug: Prednisone
    Given PO
    Other Names:
    • .delta.1-Cortisone
    • 1, 2-Dehydrocortisone
    • Adasone
    • Cortancyl
    • Dacortin
    • DeCortin
    • Decortisyl
    • Decorton
    • Delta 1-Cortisone
    • Delta-Dome
    • Deltacortene
    • Deltacortisone
    • Deltadehydrocortisone
    • Deltasone
    • Deltison
    • Deltra
    • Econosone
    • Lisacort
    • Meprosona-F
    • Metacortandracin
    • Meticorten
    • Ofisolona
    • Orasone
    • Panafcort
    • Panasol-S
    • Paracort
    • Perrigo Prednisone
    • PRED
    • Predicor
    • Predicorten
    • Prednicen-M
    • Prednicort
    • Prednidib
    • Prednilonga
    • Predniment
    • Prednisone Intensol
    • Prednisonum
    • Prednitone
    • Promifen
    • Rayos
    • Servisone
    • SK-Prednisone
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies
  • Radiation: Radiation Therapy
    Undergo radiation therapy
    Other Names:
    • Cancer Radiotherapy
    • Irradiate
    • Irradiated
    • Irradiation
    • Radiation
    • Radiation Therapy, NOS
    • Radiotherapeutics
    • Radiotherapy
    • RT
    • Therapy, Radiation
  • Drug: Triptorelin
    Anti-androgen
    Other Names:
    • 6-D-Tryptophan-LH-RH
    • 6-D-Tryptophanluteinizing Hormone-releasing Factor
    • AY-25650
    • CL-118,532
    • Detryptoreline
Study Arms  ICMJE
  • Active Comparator: RT + ADT for 24 months (De-Intensification)
    Patients undergo RT over 4-9 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin or histrelin and bicalutamide or flutamide) for 24 months in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Bicalutamide
    • Drug: Buserelin
    • Drug: Degarelix
    • Drug: Flutamide
    • Drug: Goserelin
    • Drug: Histrelin
    • Drug: Leuprolide
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Radiation: Radiation Therapy
    • Drug: Triptorelin
  • Experimental: RT + ADT for 12 months (De-Intensification)
    Patients undergo RT over 4-9 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin or histrelin and bicalutamide or flutamide) for 12 months in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Bicalutamide
    • Drug: Buserelin
    • Drug: Degarelix
    • Drug: Flutamide
    • Drug: Goserelin
    • Drug: Histrelin
    • Drug: Leuprolide
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Radiation: Radiation Therapy
    • Drug: Triptorelin
  • Active Comparator: RT + ADT for 24 months (Intensification)
    Patients undergo RT over 4-9 weeks and receive ADT as in Arm I.
    Interventions:
    • Drug: Bicalutamide
    • Drug: Buserelin
    • Drug: Degarelix
    • Drug: Flutamide
    • Drug: Goserelin
    • Drug: Histrelin
    • Drug: Leuprolide
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Radiation: Radiation Therapy
    • Drug: Triptorelin
  • Experimental: RT + ADT, Apalutamide, Abiraterone w/Pred. (Intensification)
    Patients undergo radiation therapy over 4-9 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin or histrelin) for 24 months in the absence of disease progression or unacceptable toxicity. Patients also receive apalutamide, abiraterone acetate and prednisone PO QD. Treatment repeats every 90 days for up to 8 cycles (24 months) in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Abiraterone Acetate
    • Drug: Apalutamide
    • Drug: Buserelin
    • Drug: Degarelix
    • Drug: Goserelin
    • Drug: Histrelin
    • Drug: Leuprolide
    • Drug: Prednisone
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Radiation: Radiation Therapy
    • Drug: Triptorelin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: August 11, 2020)
2478
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2038
Estimated Primary Completion Date December 31, 2033   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • PRIOR TO STEP 1 REGISTRATION
  • Pathologically proven diagnosis of adenocarcinoma of prostate cancer within 180 days prior to registration
  • High-risk disease defined as having at least one or more of the following:

    • PSA > 20 ng/mL prior to starting ADT
    • cT3a-T4 by digital exam or imaging (American Joint Committee on Cancer [AJCC] 8th edition [Ed.])
    • Gleason score of 8-10
    • Node positive by conventional imaging with a short axis of at least 1.0 cm
  • Appropriate stage for study entry based on the following diagnostic workup:

    • History/physical examination within 120 days prior to registration;
    • Bone imaging within 120 days prior to registration;

      • Note: To be eligible, patient must have no definitive evidence of bone metastases (M0) on bone scan or sodium fluoride (NaF) PET within 120 days prior to registration (negative Na F PET/CT or negative axumin or choline PET or negative fluciclovine, choline or prostate-specific membrane antigen (PSMA) PET within 120 days prior to registration is an acceptable substitute if they have been performed). Patients who have bone metastases established only fluciclovine, choline, or PSMA PET but not definitive on bone scan or Na F PET will still be eligible
    • CT or MRI of the pelvis within 120 days prior to registration (negative fluciclovine, choline, or PSMA PET within 120 days prior to registration is an acceptable substitute). As with bone staging, nodal staging for trial purposes will be based off of conventional imaging findings only
    • Patients with confirmed N1 metastases on conventional imaging (CT/MRI) as defined by > 10 mm on short axis are eligible but will be automatically assigned to the intensification study. Patients who are positive by fluciclovine, choline, or PSMA PET (i.e. N1), but whose nodes do not meet traditional size criteria for positivity (i.e. they measure =< 10 mm on either the CT or MRI portion of the PET or on a dedicated CT or MRI) will not be considered N1 for the trial and will not automatically be assigned to the intensification study
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 120 days prior to registration
  • Hemoglobin >= 9.0 g/dL, independent of transfusion and/or growth factors (within 120 days prior to registration)
  • Platelet count >= 100,000 x 10^9/uL independent of transfusion and/or growth factors (within 120 days prior to registration)
  • Creatinine clearance (CrCl) >= 30 mL/min estimated by Cockcroft-Gault equation (within 120 days prior to registration)

    • For Black patients whose renal function is not considered adequate by Cockcroft-Gault formula, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) may be used for calculating creatinine clearance for trial eligibility
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) within 120 days prior to registration

    • 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
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (within 120 days prior to registration)
  • Serum albumin >= 3.0 g/dL (within 120 days prior to 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
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (didanosine [DDI] is not permitted) with undetectable viral load within 6 months are eligible for this trial and have a CD4 count >= 200 cells/microliter within 60 days prior to registration. Note: HIV testing is not required for eligibility for this protocol. Of note, for patients with HIV in the intensification trial randomized to abiraterone acetate and apalutamide, highly active antiretroviral therapy (HAART) may need to be adjusted to medications that do not interact with abiraterone acetate and apalutamide
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable after or on suppressive therapy within 60 days prior to registration, if indicated. Note: HBV viral testing is not required for eligibility for this protocol
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Note: Any patient with a cancer (other than keratinocyte carcinoma or carcinoma in situ or low-grade non-muscle invasive bladder cancer) who has been disease-free for less than 3 years must contact the principal investigator
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
  • PRIOR TO STEP 2 RANDOMIZATION
  • Confirmation of Decipher score
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load within 60 days prior. Note: Apalutamide may interfere with HCV drugs. Patients on HCV medications should alert their infectious diseases physician if they get randomized to apalutamide due to the possibility that apalutamide can affect the bioavailability of some HCV medications. HCV viral testing is not required for eligibility for this protocol
  • For patients entering the Intensification Cohort ONLY: Patients must discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to Step 2 randomization
  • For patients entering the Intensification Cohort ONLY: Serum potassium >= 3.5 mmol/L prior to Step 2 randomization

Exclusion Criteria:

  • PRIOR TO STEP 1 REGISTRATION:
  • Definitive radiologic evidence of metastatic disease outside of the pelvic nodes (M1a, M1b or M1c) on conventional imaging (i.e. bone scan, CT scan, MRI)
  • Prior systemic chemotherapy within =< 3 years prior to registration; note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration
  • Prior radical prostatectomy
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • Current use of 5-alpha reductase inhibitor. NOTE: If the alpha reductase inhibitor is stopped prior to randomization the patient is eligible
  • Didanosine (DDI) antiretroviral therapy is not permitted
  • History of any of the following:

    • Seizure disorder
    • Current severe or unstable angina
    • New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)
    • History of any condition that in the opinion of the investigator, would preclude participation in this study
  • Evidence of any of the following at registration:

    • Active uncontrolled infection requiring IV antibiotics
    • Baseline moderate and severe hepatic impairment (Child-Pugh class B & C)
    • Inability to swallow oral pills
    • Any current condition that in the opinion of the investigator, would preclude participation in this study
  • Prior pharmacologic androgen ablation for prostate cancer is allowed only if the onset of androgen ablation (both luteinizing hormone-releasing hormone [LHRH] agonist and oral anti-androgen) is =< 60 days prior to registration; Please note: baseline PSA and testosterone must be obtained prior to the start of any ADT
  • PRIOR TO STEP 2 RANDOMIZATION:
  • Evidence of known gastrointestinal disorder affecting absorption of oral medications at registration
  • For patients entering the Intensification Cohort ONLY: Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily
  • For patients entering the Intensification Cohort ONLY: Presence of uncontrolled hypertension (persistent systolic blood pressure [BP] >= 160 mmHg or diastolic BP >= 100 mmHg). Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04513717
Other Study ID Numbers  ICMJE NRG-GU009
NCI-2020-04705 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GU009 ( Other Identifier: NRG Oncology )
NRG-GU009 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NRG Oncology
Study Sponsor  ICMJE NRG Oncology
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Paul L Nguyen NRG Oncology
PRS Account NRG Oncology
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP