Clinical Trial: NCT04513717 - My Cancer Genome

NCT04513717

Description:

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.

Related Conditions:

Prostate Adenocarcinoma

Recruiting Status:

Recruiting

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT04513717

Trial Eligibility

Document

Title

Brief Title: 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: 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*)

Clinical Trial IDs

ORG STUDY ID: NRG-GU009
SECONDARY ID: NCI-2020-04705
SECONDARY ID: NRG-GU009
SECONDARY ID: NRG-GU009
SECONDARY ID: U10CA180868
NCT ID: NCT04513717

Conditions

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

Interventions

Drug	Synonyms	Arms
Abiraterone Acetate	CB7630, Yonsa, Zytiga	RT + ADT, Apalutamide, Abiraterone w/Pred. (Intensification)
Apalutamide	ARN 509, ARN-509, ARN509, Erleada, JNJ 56021927, JNJ-56021927	RT + ADT, Apalutamide, Abiraterone w/Pred. (Intensification)
Bicalutamide	Casodex, Cosudex, ICI 176,334, ICI 176334	RT + ADT for 12 months (De-Intensification)
Buserelin	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	RT + ADT for 12 months (De-Intensification)
Degarelix	FE200486, Firmagon	RT + ADT for 12 months (De-Intensification)
Flutamide	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	RT + ADT for 12 months (De-Intensification)
Goserelin	ICI-118630	RT + ADT for 12 months (De-Intensification)
Histrelin		RT + ADT for 12 months (De-Intensification)
Leuprolide	Leuprorelin	RT + ADT for 12 months (De-Intensification)
Prednisone	.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	RT + ADT, Apalutamide, Abiraterone w/Pred. (Intensification)
Triptorelin	6-D-Tryptophan-LH-RH, 6-D-Tryptophanluteinizing Hormone-releasing Factor, AY-25650, CL-118,532, Detryptoreline	RT + ADT for 12 months (De-Intensification)

Purpose

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.

Trial Arms

Name	Type	Description	Interventions
RT + ADT for 24 months (De-Intensification)	Active Comparator	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.	Bicalutamide Buserelin Degarelix Flutamide Goserelin Histrelin Leuprolide Triptorelin
RT + ADT for 12 months (De-Intensification)	Experimental	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.	Bicalutamide Buserelin Degarelix Flutamide Goserelin Histrelin Leuprolide Triptorelin
RT + ADT for 24 months (Intensification)	Active Comparator	Patients undergo RT over 4-9 weeks and receive ADT as in Arm I.	Bicalutamide Buserelin Degarelix Flutamide Goserelin Histrelin Leuprolide Triptorelin
RT + ADT, Apalutamide, Abiraterone w/Pred. (Intensification)	Experimental	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.	Abiraterone Acetate Apalutamide Buserelin Degarelix Goserelin Histrelin Leuprolide Prednisone Triptorelin

Eligibility Criteria

        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

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	Male
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	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
Safety Issue:
Description:	Assessed based on conventional imaging. MFS will be estimated using the Kaplan-Meier method (Kaplan 1958).

Secondary Outcome Measures

Measure:	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
Safety Issue:
Description:	Will be estimated using the Kaplan-Meier method and treatment arms compared using the stratified log-rank test (Kaplan 1958).

Measure:	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
Safety Issue:
Description:	PSA failure-free survival will be estimated using the Kaplan-Meier method and treatment arms compared using the stratified log-rank test (Kaplan 1958).

Measure:	Prostate Cancer Specific Mortality (PCSM)
Time Frame:	From the date of randomization to the date of prostate cancer death, assessed up to 13 years
Safety Issue:
Description:

Measure:	Time to testosterone recovery
Time Frame:	Up to 13 years
Safety Issue:
Description:	Defined as testosterone that is non-castrate.

Measure:	Time to PSA failure or salvage therapy
Time Frame:	Up to 13 years
Safety Issue:
Description:

Measure:	Testosterone levels at the time of PSA failure and metastases
Time Frame:	Up to 13 years
Safety Issue:
Description:

Measure:	Incidence of Adverse Events
Time Frame:	Up to 13 years
Safety Issue:
Description:	Measured by the Common Terminology Criteria for Adverse Events (CTCAE ) version (v) 5.0 and Patient Reported Outcomes (PRO)-CTCAE.

Details

Phase:	Phase 3
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	NRG Oncology

Last Updated

June 1, 2021

Clinical Trials /

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