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Study of Radiation Therapy in Combination With Darolutamide + Degarelix in Intermediate Risk Prostate Cancer (SChLAP/IDC)

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ClinicalTrials.gov Identifier: NCT04176081
Recruitment Status : Not yet recruiting
First Posted : November 25, 2019
Last Update Posted : November 25, 2019
Sponsor:
Collaborators:
Prostate Cancer Canada
Bayer
Information provided by (Responsible Party):
University Health Network, Toronto

Brief Summary:

Prostate cancer (PCa) is the most frequently diagnosed cancer in men and second leading cause of cancer-related death. Men with PCa have a wide range of possible outcomes if the cancer has not spread and is classified as Intermediate-Risk PCa (IR-PCa).

The standard treatment for IR-PCa is radiation therapy (RT) with or without hormone therapy which can result in cure in some men. In other men, the cancer can come back or spread to other areas of the body. Treatment response in men with IR-PCa is highly variable. This uncertainty has led to significant under- and over-treatment.

This study aims to find out if the addition of intensive treatment (hormonal therapy: darolutamide + degarelix) to standard treatment for PCa will work better than standard treatment alone. To do this, some participants will receive hormone therapy and others will not. All participants will receive RT.

Currently, it is difficult to identify men who may require more intensive therapy. Current methods, such as using prostate specific antigen (PSA) alone, may not give the doctor enough information about who requires more intensive treatment. The researchers conducting this study believe that a particular arrangement of cancer cells [called intraductal carcinoma (IDC)] and the presence of a genetic marker called SChLAP1 can be used to identify people who would benefit from more intensive therapy.

Hormonal therapy such as with drugs called darolutamide (new drug for PCa) and Degarelix, reduce androgens (male hormones, such as testosterone) or block their effect on the cells. PCa cells require androgens to grow and divide, so removal of androgens may be effective in preventing the return of cancer following radiation therapy.

Although darolutamide has been studied in about 1000 men with PCa and seems promising and well tolerated it is considered an experimental drug, therefore it can only be used in a research study such as this one. Degarelix has been approved by Health Canada to treat PCa.

This is a phase 2, open label, randomized, controlled study and will be conducted across sites in Canada. To qualify, men must have IR-PCa and have both SChLAP1 and IDC present or both absent. Participants will be randomized to receive RT with hormone therapy or RT only. The study treatment period is 6 months for the RT + hormone therapy group. RT will take about 1-2 weeks. All participants will be followed for 5 years with multiple visits to assess safety and treatment effects.


Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Darolutamide Drug: Degarelix Radiation: Radiation Therapy Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 208 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Open-label, Multi-centre, Phase II Trial Evaluating IDC/SChLAP1 as a Biomarker for Prediction of Response to Intensified Combined Modality Treatment
Estimated Study Start Date : January 2020
Estimated Primary Completion Date : December 2028
Estimated Study Completion Date : December 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Degarelix

Arm Intervention/treatment
Active Comparator: Group 1: Radiation Therapy Only
Participants randomized to Group 1 will receive radiation therapy only.
Radiation: Radiation Therapy
The total radiotherapy dose for all subjects will be: 36.25 Gy in 5Fx. The study will not include elective nodal irradiation. Every fraction will have 3D image guidance (i.e. cone-beam CT).

Experimental: Group 2: Radiation Therapy + darolutamide + degarelix
Participants randomized to Group 2 will receive radiation therapy only + darolutamide + degarelix.
Drug: Darolutamide
Darolutamide will be administered orally as a tablet. Total daily dose is 1200 mg (2 tablets of 300 mg taken twice daily) for 6 months.
Other Names:
  • Nubeqa
  • ODM-201

Drug: Degarelix
Degarelix is administered by subcutaneous injection. The first dose of degarelix is 240 mg followed by monthly doses of 80 mg for a total treatment duration of 6 months.
Other Name: Firmagon

Radiation: Radiation Therapy
The total radiotherapy dose for all subjects will be: 36.25 Gy in 5Fx. The study will not include elective nodal irradiation. Every fraction will have 3D image guidance (i.e. cone-beam CT).




Primary Outcome Measures :
  1. Recurrence Free Survival [ Time Frame: Recurrence Free Survival will be monitored for a duration of 5 years. ]

    Recurrence Free Survival (RFS), with recurrence event defined as (whichever occurs first):

    • Biochemical failure defined as per Phoenix criteria (i.e., a rise in PSA by 2 ng/mL or more above the nadir PSA, confirmed by a second PSA measurement)
    • Clinical, radiographic, or pathological evidence of local, regional, or distant recurrence/metastasis
    • Initiation of salvage hormonal therapy
    • Death from any cause.


Secondary Outcome Measures :
  1. Difference in RFS rates (as defined in primary outcome measure) between IDC/SChLAP1 and treatment groups. [ Time Frame: 5 years ]
    To prospectively assess the role of IDC/SChLAP1 in UIR-PCa treated with curative intent radiation to predict those who derive the greatest benefit from ST-2gen-ADT.

  2. Incidence of early biochemical failure as defined by Pheonix criteria (i.e., within first 2 years of follow-up; surrogate of lethal disease). [ Time Frame: 5 years ]
    To determine the impact of ADT hormone therapy combined with radiation therapy compared to radiation therapy alone in improving rates of early failures.

  3. Rates of positive prostate biopsies (local failure) performed at time of recurrence as per standard of care. [ Time Frame: 5 years ]
    To assess the patterns of failure after ST-2gen-ADT combined with SABR compared to SABR alone.

  4. Testosterone levels [ Time Frame: 5 years ]
    To determine the effect of ST-2gen-ADT combined with SABR compared to SABR alone on the duration of castrate testosterone levels (<50 ng/dL) after treatment completion.

  5. Changes in prostate cancer-specific HRQoL as measured by abbreviated EPIC (urinary, bowel, sexual, and hormonal domains) questionnaire, as a function of treatment assignment [ Time Frame: 5 years ]
    To determine the effect of ST-2gen-ADT combined with SABR compared to SABR alone on Health Related Quality of Life (HRQOL).

  6. Rate of maximal biochemical control, defined as 2 consecutive undetectable PSA (<0.05 ng/mL) during follow-up. [ Time Frame: 5 years ]
    To determine the effect of ST-2gen-ADT combined with SABR compared to SABR alone on PSA levels.

  7. Rates of positive molecular imaging results (local, regional and/or distant failure) performed at time of recurrence as per standard of care. [ Time Frame: 5 years ]
    To assess the patterns of failure after ST-2gen-ADT combined with SABR compared to SABR alone.

  8. Changes in prostate cancer-specific HRQoL as measured by SF-12 questionnaire, as a function of treatment assignment [ Time Frame: 5 years ]
    To determine the effect of ST-2gen-ADT combined with SABR compared to SABR alone on Health Related Quality of Life (HRQOL).


Other Outcome Measures:
  1. To determine the safety of ST-2gen-ADT combined with SABR compared to SABR alone. [ Time Frame: 5 years ]
    Incidences of treatment-emergent adverse events (AE) and serious adverse events (SAE) by CTCAE v5.0

  2. To determine the tolerability of ST-2gen-ADT combined with SABR compared to SABR alone. [ Time Frame: 5 years ]
    Number of subjects discontinuing investigational products due to AE/SAEs



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • Male ≥ 18 years of age;
  • Pathologic (histologic) proven diagnosis of prostate adenocarcinoma within 180 days prior to consent;
  • PSA measurement performed within 60 days prior to consent;
  • IR-PCa as per National Comprehensive Cancer Network (NCCN) criteria (PSA >10 and < 20 ng/mL and/or Gleason score 7 and/or T-category T2b-T2c clinical or ultrasound);
  • UIR-PCa, at least one of the following:
  • 2 or 3 NCCN IR-PCa criteria;
  • Gleason score 4+3;
  • >50% diagnostic cores involved by adenocarcinoma;
  • Clinically negative (N0) stage, as defined by pelvic-CT or pelvic-MRI within 4 months prior to consent;
  • No evidence of bone metastases (M0) assessed by a bone scan within 4 months prior to consent;
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2;
  • Able and willing to provide signed informed consent as per International Conference on Harmonization - Good Clinical Practices Guidelines (ICH-GCP) and applicable regulations.

Exclusion Criteria:

  • Received any form of hormonal therapy such as bilateral orchiectomy, LHRH agonist/antagonist (e.g. goserelin, leuprolide, degarelix, etc.), anti-androgens (e.g. flutamide, bicalutamide, etc.), 5α-reductase inhibitors (e.g. finasteride, dutasteride, etc.) and/or estrogens within 1 year of consent;
  • Received prior cytotoxic therapy for prostate cancer (e.g. taxanes, mitoxantrone);
  • Currently taking medications that might cause toxicity if combined with darolutamide (see section 4.6);
  • Hemoglobin < 9.0 g/dL, independent of transfusion and/or growth factors, measured within 90 days prior to consent;
  • Platelet count < 100,000 × 109/μL, independent of transfusion and/or growth factors, within 90 days prior to consent;
  • Serum albumin < 3.0 g/dL within 90 days prior to consent;
  • Abnormal renal function, assessed within 90 days prior to consent:
  • Creatinine > 2mg/dL;
  • Glomerular filtration rate (GFR) ≤ 35 mL/min, estimated by Cockcroft-Gault formula or measured directly by 24 hour urine.
  • Abnormal liver function assessed within 90 days prior to consent:
  • Total bilirubin > 1.5 times the upper limit of normal range;
  • Aminotransferases (ALT or AST) >1.5 times the upper limit of normal range;
  • Currently on anticoagulant therapy for any indication (e.g. atrial fibrillation, valve replacement, pulmonary embolism, etc.);
  • Any cardiac events (e.g. unstable angina, myocardial infarction and/or congestive heart failure;
  • Does not agree to use highly effective method of birth control if he is having sex with a woman of childbearing potential or does not agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 4 weeks following the last dose of study drug;
  • Known hypersensitivity (or known allergic reaction) to the study treatment(s) or any of its ingredients (as listed in Investigator's brochure);
  • Planned initiation of alternative therapy for prostate cancer or investigational therapy;
  • Participation in another interventional clinical trial during and / or within 3 months of consent for this study;
  • Subject was previously randomized in this trial;
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

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): NCT04176081


Contacts
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Contact: Miran Kenk 416-946-4501 ext 3431 Miran.Kenk@uhn.ca

Locations
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Canada, Ontario
UHN Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
University Health Network, Toronto
Prostate Cancer Canada
Bayer
Investigators
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Principal Investigator: Neil Fleshner, MD UHN Princess Margaret Cancer Centre
Principal Investigator: Alejandro Berlin, MD UHN Princess Margaret Cancer Centre

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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT04176081     History of Changes
Other Study ID Numbers: SChLAP/IDC Study
First Posted: November 25, 2019    Key Record Dates
Last Update Posted: November 25, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Health Network, Toronto:
Intraductal carcinoma
SChLAP1
Radiation therapy
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases