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

Prostate Adenocarcinoma Clinical 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*)

Status Recruiting

Clinical Trial 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. 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 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.

Clinical Trial 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 (=< 0.85) 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 (> 0.85) 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 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). (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). (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). (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). (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). (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). (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). (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). (De-intensification and intensification studies)

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). (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) IV. Impact of PET use in high-risk prostate cancer

PATIENT-REPORTED OUTCOMES OBJECTIVES:

PRIMARY OBJECTIVES:

I. To compare sexual and hormonal function related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) II. To compare fatigue, as measured by the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue instrument, between the standard of care (RT plus 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study)

SECONDARY OBJECTIVES:

I. To compare depression, as measured by the PROMIS-depression, between the standard of care (RT plus 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) II. To compare depression, as measured by the PROMIS-depression, between the standard of care (RT plus 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study)

EXPLORATORY OBJECTIVES:

I. To compare cognition, as measured by the Functional Assessment of Chronic Illness Therapy-Cognitive (FACT-Cog) perceived cognitive abilities subscale, between the standard of care (RT plus 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) II. To compare bowel and urinary function related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) III. To compare fatigue, as measured by the PROMIS-Fatigue instrument, between the standard of care (RT plus 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) IV. To compare sexual and hormonal function related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study) V. To compare bowel and urinary function related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study) VI. To compare cognition, as measured by the Functional Assessment of Chronic Illness Therapy-Cognitive (FACT-Cog) perceived cognitive abilities subscale, between the standard of care (RT plus 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study)

OUTLINE: Patients are randomized to 1 of 4 arms.

DE-INTENSIFICATION STUDY (DECIPHER SCORE =< 0.85):

ARM I: Patients undergo radiation therapy (RT) over 2-11 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 2-11 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 > 0.85 OR NODE POSITIVE):

ARM III: Patients undergo RT over 2-11 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 2-11 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 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. ;

Related Conditions & MeSH terms

• Metastatic Malignant Neoplasm in the Bone
• Neoplasms
• Prostate Adenocarcinoma
• Prostatic Neoplasms
• 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

• NCT number: NCT04513717
• Study type: Interventional
• Source: NRG Oncology
• Status: Recruiting
• Phase: Phase 3
• Start date: December 15, 2020
• Completion date: December 31, 2033