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INTREPId (INTermediate Risk Erection PreservatIon Trial)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04025372
Recruitment Status : Recruiting
First Posted : July 18, 2019
Last Update Posted : July 8, 2020
Sponsor:
Collaborators:
Bayer
GenomeDx Biosciences Corp
Information provided by (Responsible Party):
Martin T. King, MD, PhD, Dana-Farber Cancer Institute

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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Bicalutamide Drug: GnRH Agonist Radiation: Radiation Therapy Drug: Darolutamide Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: INTREPId (INTermediate Risk Erection PreservatIon Trial): A Randomized Trial of Radiation Therapy and Darolutamide for Prostate Cancer
Actual Study Start Date : April 1, 2020
Estimated Primary Completion Date : September 1, 2022
Estimated Study Completion Date : September 1, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Bicalutamide+GnRH Agonist+Radiation Therapy
  • Bicalutamide is administered orally on a daily basis
  • GnRH Agonist as prescribed
  • Radiation therapy is administered starting 8-12 weeks after ADT
Drug: 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.

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

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

Experimental: Darolutamide+Radiation Therapy
  • Darolutamide is administered orally twice daily
  • Radiation therapy is administered starting 8-12 weeks after ADT
Radiation: Radiation Therapy
Radiation Therapy is a cancer treatment that uses high doses of radiation to kill cancer cells and shrink tumors.

Drug: 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




Primary Outcome Measures :
  1. The percentage of patients with a PSA nadir <= 0.5 [ Time Frame: 6 months from end of treatment ]
    A response is defined as a PSA nadir <= 0.5 within 6 months from end of treatment


Secondary Outcome Measures :
  1. The percentage of patients with good erectile function [ Time Frame: 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.

  2. PSA progression free survival [ Time Frame: 3 years ]
    PSA progression-free survival is defined as the time from randomization to PSA progression (PSA rise of 2 ng/mL above the nadir value).

  3. Metastasis free survival [ Time Frame: 3 years ]
    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.

  4. Cause specific survival [ Time Frame: 3 years ]
    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

  5. Rate of Toxicity [ Time Frame: 3 years ]
    Toxicity as measured by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  6. Quality of Life impact as measured by Expanded Prostate Cancer Index (EPIC)-26 [ Time Frame: 3 years ]
    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).

  7. Global health impact as measured by Patient-Reported Outcome Measurement Information System (PROMIS) Global Health Score [ Time Frame: 3 years ]
    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).

  8. Memory as measured by the St. Louis University Mental Status Examination (SLUMS) [ Time Frame: 3 years ]
    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).

  9. 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. [ Time Frame: 3 years ]
    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).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed prostate adenocarcinoma
  • National Cancer Center Network (NCCN) intermediate risk prostate cancer, defined as clinical T2b-T2c, Gleason 7, or PSA 10-20 ng/mL.
  • Tissue from a previous biopsy available for testing with a genomic classifier.
  • 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

  • Hepatic and Other:

    • Bilirubin ≤ 1.5 × upper limit of normal (ULN)
    • Aspartate aminotransferase (AST) ≤ 2.5 × ULN
    • Alanine aminotransferase (ALT) ≤ 2.5 × ULN
    • Serum Albumin > 3.0 g/dL
    • Serum potassium ≥ 3.5 mmol/L
  • Coagulation:

    • International Normalized Ratio (INR)
    • or Prothrombin Time (PT)
    • Activated Partial Thromboplastin Time

      • (aPTT) ≤ 1.5 × ULN (unless on prophylactic or therapeutic dosing with low molecular weight heparin)
      • 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
  • Testosterone ≥ 270 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 (even men with vasectomies) 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. 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.
  • Prostate volume as determined by MRI, CT, or ultrasound to be less than 90 cc

Exclusion Criteria:

  • Acute toxicities of prior treatments and procedures not resolved to grade 1 at baseline before randomization
  • 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, estrogens)
  • Prior treatment with second generation androgen receptor (AR) inhibitors such as 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
  • Use of estrogens or 5-α reductase inhibitors (finasteride, dutasteride) within 28 days before randomization and first generation AR inhibitors (bicalutamide, flutamide, nilutamide, cyproterone acetate) at least 28 days before screening
  • Prior radiation therapy that would result in overlap of current radiation therapy fields
  • Prior chemotherapy for prostate cancer
  • Bone metastases detected on imaging
  • Presence of brain metastases
  • Visceral metastases as assessed by abdominal or pelvic computed tomography (CT) or other imaging modality
  • 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.
  • 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, hypertension (systolic >= 160 mmHg or diastolic >= 100 mmHg), moderate or severe hepatic impairment (Child Pugh Class B or C), viral hepatitis, or human immunodeficiency virus within 6 months prior to randomization.
  • Imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Treatment should be completed for spinal cord compression.
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04025372


Contacts
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Contact: Martin T. King, MD, PhD 617-582-8939 Mtking@partners.org
Contact: Amanda Whitbeck 617-582-8939 amanda_whitbeck@dfci.harvard.edu

Locations
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United States, Massachusetts
Beth Israel Deaconness Medical Center Recruiting
Boston, Massachusetts, United States, 02115
Contact: Glenn Bubley, MD, PhD       gbubley@bidmc.harvard.edu   
Principal Investigator: Glenn Bubley, MD         
Brigham and Women Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Martin T. King, MD, PhD    617-582-8939    Mtking@partners.org   
Principal Investigator: Martin T. King, MD, PhD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Bayer
GenomeDx Biosciences Corp
Investigators
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Principal Investigator: Martin T. King, MD, PhD Brigham and Women's Hospital
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Responsible Party: Martin T. King, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT04025372    
Other Study ID Numbers: 19-202
First Posted: July 18, 2019    Key Record Dates
Last Update Posted: July 8, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Data can be shared no earlier than 1 year following the date of publication
Access Criteria: Boston Children's Hospital (BCH) - Contact the Technology & Innovation Development Office at www.childrensinnovations.org or email tido@childrens.harvard.edu Beth Israel Deaconess Medical Center (BIDMC) - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu Brigham and Women's Hospital (BWH) - Contact the Partners Innovations team at http://www.partners.org/innovation Dana-Farber Cancer Institute (DFCI) - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu Massachusetts General Hospital (MGH) - Contact the Partners Innovations team at http://www.partners.org/innovation

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Martin T. King, MD, PhD, Dana-Farber Cancer Institute:
Prostate Cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Bicalutamide
Androgen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents