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Darolutamide + Consolidation Radiotherapy in Advanced Prostate Cancer Detected by PSMA (DECREASE)

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ClinicalTrials.gov Identifier: NCT04319783
Recruitment Status : Recruiting
First Posted : March 24, 2020
Last Update Posted : September 1, 2021
Sponsor:
Collaborators:
Bayer
Peter MacCallum Cancer Centre, Australia
Information provided by (Responsible Party):
Trans Tasman Radiation Oncology Group

Brief Summary:
Darolutamide is a drug that has a proven survival benefit in non-metastatic (M0) castrate resistant prostate cancer when using conventional imaging. However, it is estimated that >90% of patients have disease apparent when using PSMA PET. This study investigates the use of local consolidation radiotherapy in this cohort of men.

Condition or disease Intervention/treatment Phase
Advanced Prostate Carcinoma Cancer of Prostate PSA Castrate Resistant Prostate Cancer Drug: Darolutamide Radiation: Radiotherapy Phase 2

Detailed Description:

This study explores the use of local consolidation therapy in the setting of Darolutamide in the initial diagnosis of metastatic castrate resistant prostate cancer (mCRPC). In the chemotherapy naïve mCRPC setting, the pattern of disease is of limited volume metastases (1-5) in 34%-40% of cases. As progression at known sites of macroscopic disease is the predominant cause of failure on systemic therapies, local consolidation therapy with stereotactic ablative body radiotherapy (SABR) may improve progression free survival (PFS) and overall survival (OS). This approach has been tested in the setting of lung cancer, in which consolidation SABR has resulted in OS benefit (HR of 0.40) in phase II studies. The novel approach of local consolidation therapy has not been tested as yet in mCRPC.

The secondary objective of this study proposal is to better understand the pattern of disease distribution at first diagnosis of CRPC. Previous studies have used conventional bone scan and CT imaging, and with these investigations the proportion of patients that are 'M0' is ~35%1. However, in the new era of PSMA PET, which is far more sensitive than conventional imaging, there exists a new group of men who are M0 on conventional imaging but are M1 on PSMA PET staging.

Thus, in the DECREASE study population, we expect the vast majority of patients with conventionally imaged 'M0 CRPC' will have disease detectable on PSMA PET scanning. In this context, the central hypothesis of this trial is that the addition of consolidation radiotherapy to darolutamide to PSMA detected sites of disease will improve the clinical outcome of patients compared to those patients receiving darolutamide alone.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 87 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Darolutamide + Consolidation Radiotherapy in Advanced Prostate Cancer Detected by PSMA
Actual Study Start Date : June 2, 2021
Estimated Primary Completion Date : June 2026
Estimated Study Completion Date : June 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Darolutamide
Darolutimide 600mg BD
Drug: Darolutamide
Darolutamide alone
Other Name: NUBEQA, Bayer HealthCare Pharmaceuticals Inc.

Experimental: Local consolidation Radiotherapy + Darolutamide
Darolutimide 600mg BD + local consolidative radiotherapy, with a biological equivalent dose of 30Gy/10fx or greater if delivered with SABR. SABR is the preferred treatment approach, however conventional radiotherapy is acceptable. To up to 5 sites of disease
Drug: Darolutamide
Darolutamide alone
Other Name: NUBEQA, Bayer HealthCare Pharmaceuticals Inc.

Radiation: Radiotherapy
Darolutamide + Consolidation Radiotherapy




Primary Outcome Measures :
  1. Undetectable PSA at 12 months [ Time Frame: 12 months ]
    Undetectable PSA at 12 months


Secondary Outcome Measures :
  1. Radiological progression free survival [ Time Frame: 36 months ]
    Radiological progression free survival

  2. Distribution of disease on baseline PSMA-PET/CT imaging [ Time Frame: 36 months ]
    Distribution of bone, nodal, visceral and recurrent primary disease on PSMA-PET/CT

  3. Biochemical progression free survival [ Time Frame: 36 months ]
    Biochemical progression free survival

  4. Treatment related adverse event [ Time Frame: 36 months ]
    Treatment related adverse events (CTCAE v 5.0)

  5. Overall survival [ Time Frame: 36 months ]
    Overall survival

  6. Patterns of disease on PSMA PET/CT after 12 weeks of commencing Darolutamide, and at time of disease progression [ Time Frame: 3 months ]
    PSMA avid disease at irradiated site / unirradiated site / bone / local / nodal / visceral



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Castration-resistant prostate cancer
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males aged 18 years or older.
  • Has provided written Informed Consent for participation in this trial.
  • Histological or cytologically confirmed adenocarcinoma of prostate without neuroendocrine differentiation or small cell features.
  • Castration-resistant prostate cancer (CRPC) defined as at least 2 consecutive PSA rises obtained at least 1 week apart in the setting of castrate testosterone levels (see below). If the patient has a history of anti-androgen use and recent withdrawal, the most recent PSA value must be obtained at least 4 weeks after anti-androgen withdrawal.
  • Castrate level of serum testosterone (<1.7 nmol/l [50 ng/dl]) on gonadotrophin - releasing hormone (GnRH) agonist or antagonist therapy or after bilateral orchiectomy. Patients who have not undergone bilateral orchiectomy must continue GnRH therapy during the study.
  • A baseline PSA level of at least 2ng per millilitre and a PSA doubling time of 10 months or less.
  • An ECOG performance status score of 0 or 1.
  • Blood counts at screening: haemoglobin ≥9.0 g/dl, absolute neutrophil count ≥1500/μl (1.5×109/l), platelet count ≥100,000/μl (100×109/l) (patient must not have received any growth factor or blood transfusion within 7 days of the haematology laboratory obtained at screening).
  • Screening values of serum alanine transaminase (ALT) and aspartate transaminase (AST) ≤2.5 x upper limit of normal (ULN), total bilirubin ≤1.5 x ULN (except patients with a diagnosis of Gilbert's disease), creatinine ≤2.0 x ULN.
  • At least 1 site of PSMA-avid disease on PSMA-PET imaging in any of the following regions:

    • Local recurrence within the prostate gland or prostate bed
    • Regional lymph node disease (below the aortic bifurcation)
    • Extra-pelvic lymph node, bone or soft tissue metastatic disease

Exclusion Criteria:

  • Patients with detectable metastases or a history of metastatic disease on conventional imaging (whole body bone scan and computed tomography (CT) of the pelvis, abdomen and chest). NOTE: Presence of pelvic lymph nodes <2 cm in short axis below the aortic bifurcation is allowed.
  • Prior treatment with: (1) second-generation androgen receptor (AR) antagonists such as enzalutamide and apalutamide, or darolutamide or other investigational AR antagonists; (2) CYP17 enzyme inhibitors, such as abiraterone acetate and orteronel; or (3) oral ketoconazole.
  • Use of estrogens or 5-α reductase inhibitors (finasteride, dutasteride) or anti-androgens (bicalutamide, flutamide, nilutamide, cyproterone acetate) within 28 days before randomisation.
  • Use of systemic corticosteroid with a dose greater than the equivalent 10 mg of prednisone/day within 28 days before randomisation.
  • Radiation therapy (external beam radiation therapy [EBRT], brachytherapy, or radiopharmaceuticals) within 12 weeks prior to randomisation.
  • Initiation of treatment with an osteoclast-targeted therapy (bisphosphonate or denosumab) to prevent skeletal-related events within 12 weeks before randomisation. NOTE: Patients receiving osteoclast-targeted therapy to prevent bone loss at a dose and schedule indicated for osteoporosis may continue treatment at the same dose and schedule, providing it was commenced at least 28 days before randomisation.
  • Any of the following within 6 months before randomisation: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV.
  • Uncontrolled hypertension as indicated by a systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg at screening.
  • Prior malignancy. NOTE: Adequately treated basal cell or squamous cell carcinoma of skin or superficial bladder cancer that has not spread behind the connective tissue layer (i.e., pTis, pTa, and pT1) is allowed, as well as any other cancer for which the last anti-cancer therapeutic intervention has been completed - 5 years ago and from which the patient has been disease-free.
  • Gastrointestinal disorder or procedure that expects to interfere significantly with the absorption of study treatment.
  • Unable to swallow study medications and comply with study requirements.

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): NCT04319783


Contacts
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Contact: Rebecca Montgomery +61 2 4014 3910 decrease@trog.com.au
Contact: Rebekah Di Rico +61 2 4014 3915 decrease@trog.com.au

Locations
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Australia, Victoria
Peter MacCallum Cancer Center Recruiting
Melbourne, Victoria, Australia, 3002
Contact: Lisa Selbie    +61 3 96561760    lisa.selbie@petermac.org   
Principal Investigator: Arun Azad         
Sponsors and Collaborators
Trans Tasman Radiation Oncology Group
Bayer
Peter MacCallum Cancer Centre, Australia
Investigators
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Study Chair: Shankar Siva Peter MacCallum Cancer Centre, Australia
Study Chair: Arun Azad Peter MacCallum Cancer Centre, Australia
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Responsible Party: Trans Tasman Radiation Oncology Group
ClinicalTrials.gov Identifier: NCT04319783    
Other Study ID Numbers: TROG 19.06
U1111-1242-9233 ( Other Identifier: UTN- World Health Organisation )
First Posted: March 24, 2020    Key Record Dates
Last Update Posted: September 1, 2021
Last Verified: August 2021
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
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Trans Tasman Radiation Oncology Group:
Darolutamide
Consolidation Radiotherapy
PSA
PSMA PET
Prostate Cancer
Advanced Prostate Cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases