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Management of Oligoprogressive Castration Resistant Prostate Cancer (PCS X)

Phase 2
Recruiting
Conditions
Metastatic Prostate Cancer
Castration-resistant Prostate Cancer
Interventions
Registration Number
NCT04070209
Lead Sponsor
Sir Mortimer B. Davis - Jewish General Hospital
Brief Summary

This is the first pilot phase II trial assessing the response of SBRT layered on Darolutamide (BAY1841788) on RPFS and deferring palliative second line systemic therapy in M0CRPC with oligoprogression.

Detailed Description

Metastases-directed therapy with stereotactic body radiation therapy (SBRT) is emerging as a new treatment option for solid tumor patients with a limited number of metastases (\< 5) at the time of recurrence/progression, so called oligoprogression therapy. As such, oligoprogression is defined as prostate cancer patients with castration resistance and no metastases (M0CRPC) who are receiving ADT and new generation hormonal therapy (enzalutamide, apalutamide or darolutamide) as standard of care, and who are then progressing to oligometastases. The new generation hormonal therapy used in this study will be darolutamide (ODM-201). The rationale behind this approach has been to delay the start of palliative systemic therapies that are most often toxic and associated with a negative impact on patient's quality of life, as well as being more costly. However, to date, there are no prospective published data or ongoing studies that are looking into non metastatic castration resistant prostate cancer (M0CRPC) patients who progress to oligometastases (oligoprogression). To this end, we are proposing this pilot phase II trial to assess the impact of SBRT on radiological progression-free survival (RPFS) of M0CRPC patients who are receiving darolutamide and progress to oligometastatic disease (oligoprogression).

Prostate cancer patients with castration resistance and no metastases (M0CRPC) diagnosed by bone scan and CT scan or MRI will be recruited in this phase II and initiate darolutamide while continuing on ADT (Part 1 of the study), if not receiving darolutamide prior to study entry already. Patients who then progress to wide spread metastases or metastases situated at locations not amenable to ablative therapy will be excluded and treated with second line therapy as per the treating physician. Patients with oligoprogression (\< 5 mets) and amenable to ablative therapy will be then treated with SBRT or surgery as an ablative therapy if SBRT is not feasible (Part 2 of the study). All patients will continue to receive non-interrupted LHRH agonist, PSA testing every 6-12 weeks and re-imaging every 6 months. Imaging will also be repeated at the appearance of symptoms or at PSA progression, whichever occurs first and this schedule continues until disease progression.

This is the first pilot phase II trial assessing the response of SBRT layered on darolutamide on RPFS and deferring palliative second line systemic therapy in M0CRPC with oligoprogression. This phase II will consist of 66 M0CRPC patients treated with darolutamide, of which we anticipate 48 will be eligible for SBRT.

Recruitment & Eligibility

Status
RECRUITING
Sex
Male
Target Recruitment
66
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Darolutamide (BAY1841788)+ SBRTSBRTCRPC subjects will receive LHRH agonist in combination with the new generation of hormonal therapy Darolutamide (300mg). Subjects who progress on LHRH + Darolutamide and develop oligometastases will receive SBRT
Darolutamide (BAY1841788)+ SBRTDarolutamide (BAY1841788)CRPC subjects will receive LHRH agonist in combination with the new generation of hormonal therapy Darolutamide (300mg). Subjects who progress on LHRH + Darolutamide and develop oligometastases will receive SBRT
Primary Outcome Measures
NameTimeMethod
Radiographic Progression-free Survival5 years

Time from first day of SBRT until confirmed second radiological progression or start of new antineoplastic therapy

Secondary Outcome Measures
NameTimeMethod
PSA response5 years

PSA value and onset of biochemical failure will be recorded

Functional Assessment of Cancer Therapy-Prostate5 years

Evaluate the impact of the treatment on the patient's quality of life using the FACT-P questionnaire

Overall Survival5 years

Time from randomization until death from any cause

Quality of Life - Fatigue5 years

Evaluate the impact of the treatment on the patient's quality of life using the Brief Fatigue Inventory (BFI) questionnaire

Quality of Life - Pain5 years

Evaluate the impact of the treatment on the patient's quality of life using the Brief Pain Inventory (BPI) questionnaire

Toxicity of ODM-2015 years

To determine acute and late toxicity due to ODM-201, scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Time to Subsequent Systemic Antineoplastic Therapy5 years

Time to the administration of subsequent antineoplastic systemic therapy

Disease Specific Survival5 years

Time from randomization until death due to prostate cancer

Time to Skeletal-related Event (SRE)5 years

Date of first SRE will be recorded

Local Control5 years

To evaluate the impact of SBRT on oligometastases progression by radiographic imaging or the start of new antineoplastic therapy.

Trial Locations

Locations (10)

Prostate Cancer Centre

🇨🇦

Calgary, Alberta, Canada

Centre of Applied Urology Research

🇨🇦

Halifax, Nova Scotia, Canada

St. Joseph's Healthcare Hamilton

🇨🇦

Hamilton, Ontario, Canada

Service d'urologie et Centre de la prostate

🇨🇦

Longueuil, Quebec, Canada

Centre hospitalier de l'Université de Montréal (CHUM)

🇨🇦

Montreal, Quebec, Canada

Hôpital Maisonneuve-Rosemont

🇨🇦

Montréal, Quebec, Canada

Sir Mortimer JGH

🇨🇦

Montréal, Quebec, Canada

L'Hôtel-Dieu de Québec (CHUQ)

🇨🇦

Québec city, Quebec, Canada

Hôpital Fleurimont (CHUS)

🇨🇦

Sherbrooke, Quebec, Canada

Centre hospitalier affilié universitaire régional (CHAUR)

🇨🇦

Trois-Rivières, Quebec, Canada

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