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Darolutamide + Consolidation Radiotherapy in Advanced Prostate Cancer Detected by PSMA

PHASE2RECRUITING

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.

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Study details:

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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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

≥ 18 years of age and provided written Informed Consent

Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features

Castration-resistant prostate cancer, defined as at least 2 consecutive PSA rises obtained at least 1 week apart in the setting of castrate testosterone levels

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

A baseline PSA level of at least 1ng per millilitre and a PSA doubling time of 10 months or less

Adequate bone marrow reserve and organ function Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

At least 1 site of PSMA-avid disease on PSMA-PET/CT imaging in any of the following regions; At least 1 site of PSMA-avid disease on PSMA-PET/CT 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

Prior treatment with second-generation androgen receptor (AR) antagonists, CYP17 enzyme inhibitors or oral ketoconazole

Use of oestrogens or 5-α reductase inhibitors or anti-androgens 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

Radiotherapy within 12 weeks prior to randomisation

Initiation of treatment with an osteoclast-targeted therapy to prevent skeletal-related events within 12 weeks 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

Prior malignancy

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

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: Male

Things to know

Study dates

Study start: 2021-06-02

Primary completion: 2026-06-01

Study completion finish: 2026-06-01

Study type

TREATMENT

Phase

PHASE2

Trial ID

NCT04319783

Intervention or treatment

DRUG: Darolutamide

RADIATION: Radiotherapy

Conditions

• Advanced Prostate Carcinoma
• Cancer of Prostate
• PSA
• Castrate Resistant Prostate Cancer

Image related to Advanced Prostate Carcinoma

Condition: Advanced Prostate Carcinoma, Cancer of Prostate and more
DRUG: Darolutamide and other drugs
Waratah, New South Wales, Australia and more
Sponsor: Trans Tasman Radiation Oncology Group

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

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Find a site

Closest Location:

Calvary Mater Newcastle

Research sites nearby

Select from list below to view details:

Calvary Mater Newcastle
Waratah, New South Wales, Australia
Townsville University Hospital
Douglas, Queensland, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Darolutamide Darolutimide 600mg BD	DRUG: Darolutamide Darolutamide alone
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

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Undetectable PSA at 12 months	Undetectable PSA at 12 months	12 months

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Radiological progression free survival	Radiological progression free survival	36 months
Distribution of disease on baseline PSMA-PET/CT imaging	Distribution of bone, nodal, visceral and recurrent primary disease on PSMA-PET/CT	36 months
Biochemical progression free survival	Biochemical progression free survival	36 months
Treatment related adverse event	Treatment related adverse events (CTCAE v 5.0)	36 months
Overall survival	Overall survival	36 months
Patterns of disease on PSMA PET/CT after 12 weeks of commencing Darolutamide, and at time of disease progression	PSMA avid disease at irradiated site / unirradiated site / bone / local / nodal / visceral	3 months

Frequently Asked Questions

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References

Clinical Trials Gov: Darolutamide + Consolidation Radiotherapy in Advanced Prostate Cancer Detected by PSMA