This research study is comparing the use of a new form of hormonal therapy used with radiation as a possible treatment for intermediate risk prostate cancer. More specifically, this research would help determine whether this new form of hormonal therapy is as effective as the standard hormone therapy while also preserving erectile function.
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied. In this research study, the investigators are looking at whether the novel form of hormonal therapy, called Darolutamide, when paired with radiation therapy will provide the same quality of care as the current standard treatments available for men with this type of cancer. Darolutamide prevents testosterone from signaling throughout the body. Although studies have shown that Darolutamide has activity in more advanced forms of prostate cancer, the activity of Darolutamide is unknown in intermediate risk prostate cancer treated with radiation therapy. The U.S. Food and Drug Administration (FDA) has not approved Darolutamide as a treatment for any disease. The current standard of care treatments available to men with this type of cancer are radiation therapy with or without androgen deprivation therapy (ADT) involving a gonadotropin releasing hormone agonist plus bicalutamide (both FDA-approved) or surgery. ADT works by depriving the body of testosterone which "feeds" prostate cancer cells and weakens prostate cancer cells from repairing damage caused by radiation therapy. In addition, the investigator will be assessing erectile function at baseline, during and after treatment to determine if short-term erectile function can be preserved without sacrificing long-term disease control.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
234
Bicalutamide is categorized as an antiandrogen. Antiandrogens are substances that block the effects of testosterone. Cancer of the prostate depends on the male hormone testosterone for its growth. If the amount of testosterone is reduced it is possible to slow down or shrink the cancer.
In men, GnRH agonists cause the testicles to stop making testosterone. Some GnRH agonists are used to treat prostate cancer.
Radiation Therapy is a cancer treatment that uses high doses of radiation to kill cancer cells and shrink tumors.
Stamford Hospital
Stamford, Connecticut, United States
Beth Israel Deaconness Medical Center
Boston, Massachusetts, United States
Brigham and Women Hospital
Boston, Massachusetts, United States
The percentage of patients with a PSA nadir <= 0.5
A response is defined as a PSA nadir \<= 0.5 within 6 months from end of treatment
Time frame: 6 months from end of treatment
The percentage of patients with good erectile function at 3 months from end of treatment
Good erectile function is defined as firm enough for masturbation or foreplay' or 'firm enough for intercourse' responses to the question "How would you describe the usual quality of your erections during the past 4 weeks" on the EPIC-26 questionnaire.
Time frame: 3 months from end of treatment
PSA progression free survival
PSA progression-free survival is defined as the time from randomization to PSA progression (PSA rise of 2 ng/mL above the nadir value).
Time frame: 3 years
Metastasis free survival
Metastasis-free survival is defined as the time from randomization to distant metastasis (including bony or visceral) identified on imaging or pathologically, or death due to any cause, or censored at date last known alive.
Time frame: 3 years
Cause specific survival
Cause specific survival is defined as the interval from the date of randomization to the date of last known follow-up alive, or the date of death from each of the following causes: prostate cancer, cardiovascular disease, other causes
Time frame: 3 years
To evaluate differences in long-term maintenance of erectile function
The answers to EPIC-26 question "How would you describe the usual quality of your erections during the past 4 weeks" from treatment start to the end of follow up at three years show how erectile function has been affected over time.
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Darolutamide belongs to a class of drugs called androgen receptor inhibitors. In the body, these agents compete with androgens for binding to the androgen receptor, which reduces the ability of androgens to promote the growth of prostate cancer cells
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Dana-Farber/Brigham and Women's Cancer Center at Milford Regional Medical Center
Milford, Massachusetts, United States
Dana-Farber/Brigham and Women's Cancer Center in Clinical Affiliation with South Shore Hospital
South Weymouth, Massachusetts, United States
Washington University School of Medicine in St. Louis
St Louis, Missouri, United States
XCancer Omaha / Urology Cancer Center
Omaha, Nebraska, United States
NYU Long Island
Garden City, New York, United States
NYU Langone Health
New York, New York, United States
...and 1 more locations
Time frame: 3 years
Rate of Toxicity
Toxicity as measured by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: 3 years
Quality of Life impact as measured by Expanded Prostate Cancer Index (EPIC)-26
EPIC-26 is a shortened version of the EPIC questionnaire that evaluates subject's urinary incontinence, urinary irritation/obstruction, bowel, sexual, and hormonal domains. EPIC is a robust prostate-cancer health-related QOL instrument that measures a broad spectrum of symptoms and has been widely validated. For each domain, scales range between 0 (worse) and 100 (better).
Time frame: 3 years
Global health impact as measured by Patient-Reported Outcome Measurement Information System (PROMIS) Global Health Score
PROMIS is a standardized method for measuring an individual's global health in terms of physical and mental functioning. Scores range from 23.4 (worse) to 63.3 (better).
Time frame: 3 years
Memory as measured by the St. Louis University Mental Status Examination (SLUMS)
SLUMS is a single-page exam that measures mild cognitive changes. Scores can be divided as 0-20 (mild dementia), 21-26 (mild cognitive disorder), and 27-30 (normal).
Time frame: 3 years
Quality of Life impact as measured by Patient-Reported Outcome Measurement Information System (PROMIS) Sexual Function and Satisfaction Measures (SexFS) Brief Profile Version 2.0.
The PROMIS SexFS Brief Profile v2.0 measures a range of sexual activities, symptoms, functioning, and evaluation of experiences over the past 30 days. Scores range from 31.6 (worse) to 62.7 (better).
Time frame: 3 years
Testosterone kinetics
For arm 1, time to Testosterone Recovery is defined as the time from randomization to the date at which the testosterone level returns to a normal level on the assay used, or censored at date of last disease evaluation for those whose testosterone has not reached a normal level. Furthermore, testosterone levels will be compared between arms 1 and 2 at EOT and yearly intervals after EOT.
Time frame: 3 years
Cardiovascular events
Time to cardiovascular event is defined as the time from randomization to the date at which the first cardiovascular event occurs. Censoring occurs at date of last disease evaluation for those who did not have a cardiovascular event. Cardiovascular events consisting of myocardial infarction, stroke, deep venous thrombosis, or pulmonary embolism will be collected during study visits and follow-ups.
Time frame: 3 years
Time to re-initiation of ADT
Time to re-initiation of ADT is defined as the time from randomization to the date at which ADT is reinitiated. Censoring occurs at date of last disease evaluation for those who are not restarted on ADT.
Time frame: 3 years