Title
Parallel Phase III Randomized Trials of Genomic-Risk Stratified Unfavorable Intermediate Risk Prostate Cancer: De-intensification and Intensification Clinical Trial Evaluation (Guidance)

Description
This phase III trial uses the Decipher risk score to guide intensification (for higher Decipher gene risk) or de-intensification (for low Decipher gene risk) of treatment to better match therapies to an individual patient's cancer aggressiveness. The Decipher risk score evaluates a prostate cancer tumor for its potential for spreading. In patients with low risk scores, this trial compares radiation therapy alone to the usual treatment of radiation therapy and hormone therapy (androgen deprivation therapy). Radiation therapy uses high energy x-rays or particles to kill tumor cells and shrink tumors. Androgen deprivation therapy blocks the production or interferes with the action of male sex hormones such as testosterone, which plays a role in prostate cancer development. Giving radiation treatment alone may be the same as the usual approach in controlling the cancer and preventing it from spreading, while avoiding the side effects associated with hormonal therapy. In patients with higher Decipher gene risk, this trial compares the addition of darolutamide to usual treatment radiation therapy and hormone therapy, to usual treatment. Darolutamide blocks the actions of the androgens (e.g. testosterone) in the tumor cells and in the body. The addition of darolutamide to the usual treatment may better control the cancer and prevent it from spreading.

Objective
Primary Objective:

De-Intensification Study:
To determine whether men with National Comprehensive Cancer Network (NCCN) unfavorable intermediate risk (UIR) prostate cancer and lower Decipher genomic risk (Decipher score < 0.40) treated with RT alone instead of 6 months ADT + RT experience non-inferior rate of distant metastasis.

Intensification Study:
To determine whether men with NCCN UIR prostate cancer who are in the higher genomic risk (Decipher score ?0.40) will have a superior metastasis-free survival through treatment intensification with darolutamide added to the standard of RT plus 6 months ADT.

Treatment Experimental: Arm I (RT)
Patients undergo RT using a recognized regimen (2-3 days a week or 5 days a week for 2-11 weeks) in the absence of disease progression or unacceptable toxicity.

Experimental: Arm II (RT, ADT)
Patients undergo RT as Arm I. Patients also receive ADT consisting of leuprolide, goserelin, buserelin, histrelin, triptorelin, degarelix, or relugolix at the discretion of the treating physician, for 6 months in the absence of disease progression or unacceptable toxicity. Patients may also receive bicalutamide or flutamide for 0, 30 or 180 days.

Experimental: Arm III (RT, ADT)
Patients receive treatment as in Arm II.

Experimental: Arm IV (RT, ADT, darolutamide)
Patients receive RT and ADT as in Arm II. Patients also receive darolutamide PO BID on days 1-90. Treatment repeats every 90 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

Key Eligibility To view the full trial eligibility, please see this trial's ClinicalTrials.gov record.

Applicable Disease Sites
Prostate

Participating Institutions
Bellin Memorial Hospital/Cancer Team at Bellin Health; Johnson Creek, UW Cancer Center; UW Cancer Center at ProHealth; UW Health Carbone Cancer Center Rockford; UW Health Eastpark Medical Center; UW Health University Hospital