INTREPId (INTermediate Risk Erection PreservatIon Trial)

NCT ID: NCT04025372

Last Updated: 2025-12-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 234 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-01
• Study Completion Date: 2028-03-01

Brief Summary

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.

Detailed Description

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bicalutamide+GnRH Agonist+Radiation Therapy

• Bicalutamide is administered orally on a daily basis
• GnRH Agonist as prescribed
• Radiation therapy is administered starting 4-16 weeks after ADT

Group Type: EXPERIMENTAL

Bicalutamide

Intervention Type: DRUG

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.

GnRH Agonist

Intervention Type: DRUG

In men, GnRH agonists cause the testicles to stop making testosterone. Some GnRH agonists are used to treat prostate cancer.

Radiation Therapy

Intervention Type: RADIATION

Radiation Therapy is a cancer treatment that uses high doses of radiation to kill cancer cells and shrink tumors.

Darolutamide+Radiation Therapy

• Darolutamide is administered orally twice daily
• Radiation therapy is administered starting 4-16 weeks after Darolutamide

Group Type: EXPERIMENTAL

Radiation Therapy

Intervention Type: RADIATION

Radiation Therapy is a cancer treatment that uses high doses of radiation to kill cancer cells and shrink tumors.

Darolutamide

Intervention Type: DRUG

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

Interventions

Bicalutamide

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.

Intervention Type: DRUG

GnRH Agonist

In men, GnRH agonists cause the testicles to stop making testosterone. Some GnRH agonists are used to treat prostate cancer.

Intervention Type: DRUG

Radiation Therapy

Radiation Therapy is a cancer treatment that uses high doses of radiation to kill cancer cells and shrink tumors.

Intervention Type: RADIATION

Darolutamide

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed prostate adenocarcinoma by biopsy within 1 year (365 days) from registration. The most recent biopsy will determine eligibility
• National Cancer Center Network (NCCN) intermediate risk prostate cancer, defined as clinical T2b-T2c, Gleason 7, or PSA 10-20 ng/mL. Patients who only have radiographic evidence of T3 disease (i.e. extracapsular extension, or seminal vesical invasion radiographically) will not be excluded.
• Able to characterize the number of unfavorable intermediate risk factors below:

• 2-3 intermediate risk factors

• T2b-T2c
• Gleason 7
• PSA 10-20 ng/mL
• Gleason 4+3 disease
• Percent positive cores ≥ 50%
• Tissue available for submission for Decipher genomic score from archived tissue. Patients who had tissue sent to Decipher but did not have sufficient tissue for processing will not be excluded. Patients who already have a Decipher score must present official report documentation.
• Able to undergo radiation therapy with curative intent
• Age ≥ 18 at the time of consent.
• Demonstrate adequate organ function (hematologic, renal, hepatic) within 3 months of registration
• System Laboratory Value
• Hematological:

• Platelet count (plt) ≥ 100,000/ µL
• Hemoglobin (Hgb) ≥ 9 g/dL
• Absolute neutrophil count (ANC) ≥ 1000 cells/µL
• Renal:

• Glomerular filtration rate (GFR) ≥ 45 mL/min

• CKD-EPI equation will be used to calculate GFR
• Hepatic and Other:

• Bilirubin ≤ 1.5 × upper limit of normal (ULN)

• In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin; if direct bilirubin is ≤1.5 × ULN, subject may be eligible
• Aspartate aminotransferase (AST) ≤ 2.5 × ULN
• Alanine aminotransferase (ALT) ≤ 2.5 × ULN
• Serum Albumin > 3.0 g/dL
• Serum potassium ≥ 3.5 mmol/L
• Endocrine:

• Testosterone ≥ 150 ng/dL
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Good erectile function, as assessed by 'firm enough for masturbation or foreplay' or 'firm enough for intercourse' response to the question "How would you describe the usual quality of your erections during the past 4 weeks" on the EPIC-26 questionnaire
• Agrees to use a condom and another effective method of birth control if he is having sex with a woman of childbearing potential (defined as a premenopausal female capable of becoming pregnant) OR agrees 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. It is recommended that men who have had a vasectomy more than a year prior to trial registration use a condom. Must also agree not to donate sperm.
• Ability to understand and comply with study procedures for the entire length of the study as determined by the site investigator or protocol designee
• Written informed consent and HIPAA authorization for release of personal health information prior to registration. Note: HIPAA authorization may be included in the informed consent or obtained separately. Subject must have the ability to understand and willingness to sign the written informed consent document.
• Ability to swallow pills.
• For patients in whom SBRT/combination RT stratification is pre-specified, prostate volume as determined by MRI, CT, or ultrasound to be less than 90 cc.

Exclusion Criteria

• Prior surgical, cryotherapy, or high-intensity focused ultrasound for prostate cancer
• Prior orchiectomy or hormonal therapy (gonadotropin releasing hormone (GnRH) agonists, non-steroidal anti-androgens)
• Prior treatment with a first generation AR inhibitor (e.g. bicalutamide, flutamide, nilutamide, cyproterone acetate) or second generation AR inhibitor (e.g.Enzalutamide, Apalutamide, or Darolutamide)
• Prior treatment with other investigational AR inhibitors, CYP17 enzyme inhibitor such as abiraterone acetate, TAK-700, or oral ketoconazole longer than 28 days
• Prior use of estrogens; patients who have used testosterone injections must have ceased utilization within 90 days prior to screening testosterone. Patients who have used any other type of testosterone supplementation (e.g. patches) must have ceased utilization within 45 days prior to screening testosterone.
• Use of 5-α reductase inhibitors (finasteride, dutasteride) within 28 days of randomization.
• Prior radiation therapy that would result in overlap of current radiation therapy fields
• Prior chemotherapy for prostate cancer
• Clinically positive lymph nodes by imaging, sampling, or dissection. Patients with lymph nodes greater than 1.5 cm on short axis will require a negative biopsy for eligibility.
• Metastatic disease, as assessed by abdominal or pelvic computed tomography (CT) or other imaging modality. Patients with 3 intermediate risk factors will require a CT abdomen/pelvis and a bone scan or PET imaging (PSMA PET/CT, fluciclovine PET/CT, etc.).
• Erectile aids other than oral phosphodiesterase (PDE)-5 inhibitors
• History of any of the following: Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure New York Heart Association (NYHA) class III or IV, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), clinically significant ventricular arrhythmias, moderate or severe hepatic impairment (Child Pugh Class B or C), viral hepatitis, or human immunodeficiency virus within 6 months prior to randomization.
• Current untreated hypertension (systolic >= 160 mmHg or diastolic >= 100 mmHg). Patients with one blood pressure reading with systolic < 160 mmHg and diastolic < 100 mmHg within 90 days of registration would be eligible for study.
• Individuals with a history of another malignancy are not eligible if:

• The cancer is under active treatment
• The cancer can be seen on radiology scans
• If they are off cancer treatment, but in the opinion of their oncologist, have a high risk of relapse within 5 years.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (NCI-CTCAE version 5.0 Grade 2), psychiatric illness or social situations that would limit compliance with study requirement
• Any condition that, in the opinion of the site investigator, would preclude participation in this study

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

Decipher Biosciences

UNKNOWN

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Martin T. King, MD, PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Martin T. King, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Stamford Hospital

Stamford, Connecticut, United States

Beth Israel Deaconness Medical Center

Boston, Massachusetts, United States

Brigham and Women Hospital

Boston, Massachusetts, United States

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

Associated Medical Professionals of NY

Syracuse, New York, United States

Countries

United States

References

Roy A, Green O, Brenneman R, Bosch W, Gay HA, Michalski JM, Baumann BC. Assessing Inter-Fraction Changes in The Size and Position of The Penile Bulb During Daily MR-Guided Radiation Therapy to The Prostate Bed: Do We Need to Adjust How We Plan Radiation in The Post-Radical Prostatectomy Setting to Reduce Risk of Erectile Dysfunction? Clin Genitourin Cancer. 2022 Jun;20(3):e227-e232. doi: 10.1016/j.clgc.2022.01.006. Epub 2022 Jan 11.

Reference Type: DERIVED

PMID: 35153154 (View on PubMed)

Other Identifiers

19-202

Identifier Type: -

Identifier Source: org_study_id