January 12 2022
Parallel Phase III Randomized Trials for High-Risk Prostate Cancer Evaluation De-Intensification for Lower Genomic Risk and Intensification of Concurrent Therapy for Higher Genomic Risk with Radiation (PREDICT-RT*)
*Prostate RNA Expression/Decipher to Individualize Concurrent Therapy with Radiation
The phase III randomized study NRG-GU009, also known as the PREDICT-RT Study, recently re-opened for high-risk prostate cancer patient enrollment in December 2021. Patients who participate in this trial will need to submit tissue for Decipher analysis at registration. Decipher scores will determine if patients will participate in the De-Intensification portion or the Intensification portion of the study.
The trial was temporarily closed in 2021 to accrual to allow for an amendment for a treatment change in light of the results presented at the February 2021 Annual Meeting of the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium. [Rathkopf, et al. Final results from ACIS, a randomized, placebo (PBO)-controlled double-blind phase 3 study of apalutamide (APA) and abiraterone acetate plus prednisone (AAP) versus AAP in patients (pts) with chemo-naïve metastatic castration-resistant prostate cancer (mCRPC). Journal of Clinical Oncology 2021 39:6_suppl, 9-9]
The amendment to the NRG-GU009 trial removed the study drugs abiraterone acetate and prednisone from the intervention arm of the intensification study in the trial.
“It would be relatively easy to stratify patients with high-risk prostate cancer using genomic methodologies such as a Decipher test on the prostate biopsy,” stated Paul Nguyen, MD, the Baldwin-Politi Distinguished Chair in Oncology at the Brigham and Women’s Hospital and Dana-Farber Cancer Institute and Professor of Radiation Oncology at Harvard Medical School, and the Co-Principal Investigator of the NRG-GU009 trial. “On NRG-GU009 we are utilizing patient populations, divided by Decipher score, to categorize participants into better and worse prognostic categories and then test the lower risk prostate cancer group with a de-intensified treatment schedule as well as the higher-risk prostate cancer group with a more intensive treatment.”
Patients with a Decipher score of less than or equal to 0.85 will be assigned to the De-Intensification study. Patients on the De-Intensification study will be stratified by Decipher score range, boost type, prior pelvic treatment, and ACE-27 comorbidity. Following stratification, patients on the De-intensification study will be randomly assigned to treatment arm 1 or arm 2. Patients on treatment arm 1 will receive the standard of care for this type of cancer which includes radiotherapy (RT) and 24 months of androgen deprivation therapy (ADT). Patients on treatment arm 2 will receive RT and 12 months of ADT.
Patients with a Decipher score greater than 0.85 or are considered node positive will be assigned to the Intensification study. Patients on the Intensification study will be stratified by boost type, prior pelvic treatment, and nodal status. Following stratification, patients on the Intensification study will be randomly assigned to treatment arm 3 or arm 4. Patients on treatment arm 3 will receive the standard of care RT with 24 months of ADT, whereas patients on treatment arm 4 will receive RT, 24 months of ADT, and 24 months of apalutamide.
The primary objective of the De-intensification study is to determine if men with high-risk prostate cancer in a lower Decipher score range can be treated with less ADT and achieve similar metastasis-free survival results. The primary objective of the Intensification study is to determine if the addition of apalutamide to the standard of care can help improve metastasis-free survival for men with high-risk prostate cancer in a higher Decipher score range.
“As more men continue to receive high-risk and metastatic prostate cancer diagnoses, it is exceptionally important to be sure we are seeking treatment that help to improve outcomes and quality of life for this patient population,” added A. Oliver Sartor, MD, the Medical Director of the Tulane Cancer Center at Tulane University School of Medicine. “We hypothesize that the de-intensification portion of this study could allow us to achieve similar results with half the timeline of the standard of care treatment and the intensification study could potentially allow us to achieve better results for survival outcomes of these patients through more intensive treatment measures.”
NRG-GU009 will also be comparing overall survival, PSA failure or start of salvage treatment, PSA failure-free survival with non-castrate testosterone and no additional therapies, metastasis-free survival based on standard or molecular imaging, prostate cancer-specific mortality, testosterone levels at time of PSA failure and metastases, time to testosterone recover, and adverse events between the standard of care treatment and either the de-intensification treatment or the intensification treatment.
Learn more about this trial on ClinicalTrials.gov
The protocol documents and materials are located on the CTSU website.