Clinical trial NCT04557501: PSMA PET/CT Guided Intensification of Therapy in Patients at Risk of Advanced Prostate Cancer
Official title: PSMA PET/CT Guided Intensification of Therapy in Patients at Risk of Advanced Prostate Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Prostate Cancer
Lead sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor class: OTHER
Collaborators: name: Canadian Cancer Society (CCS)
name: Lantheus Medical Imaging
name: British Columbia Cancer Agency
name: London Health Sciences Centre
name: Princess Margaret Hospital, Canada
name: Tom Baker Cancer Centre
name: McMaster University
name: Institute of Health Economics, Canada
name: Queen's University
First posted: 2020-09-21
Enrollment: 800
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Through the conduct of a Phase III randomized controlled trial, investigators plan to: 1) determine if PSMA PET/CT guided intensification of radiotherapy or surgery improves cancer outcomes compared to conventional imaging-guided therapy in patients at risk of advanced disease, 2) evaluate its impact on toxicity and quality of life, and 3) measure the cost-effectiveness of the PSMA PET/CT guided approach.

Participants with high-risk prostate cancer planned for curative-intent standard-of-care radiotherapy or surgery, or with biochemical failure after radical prostatectomy planned for salvage radiotherapy will be enrolled over 3 years (n=776). Those randomized to the investigational arm will have PSMA PET/CT prior to therapy. Based on the imaging results, treating physicians will intensify radiotherapy or surgery unless widely metastatic disease is found, in which case systemic therapy will be intensified.

Detailed description: PSMA PET/CT, particularly with the new generation \[18F\]DCFPyL radiotracer, has substantially improved our ability to detect sites of prostate cancer compared with conventional imaging alone. When combined with innovative radiotherapeutic and surgical techniques that can now safely target and ablate such disease sites, next generation imaging is now poised to transform the therapeutic paradigm for patients at risk of advanced cancer.

Investigators postulate that intensification of radiotherapy or surgery based on the results of PSMA PET/CT will improve cancer control outcomes in a cost-effective manner, with minimal toxicity, and an overall improvement in quality of life in the longer term.

Investigators expect to show that PSMA PET/CT will have a direct and profound impact on radiotherapy and surgery practice, translating to improved failure-free survival outcomes in patients at risk of advanced prostate cancer. The subset of patients potentially impacted is broad, including patients recurring after prostatectomy and newly presenting patients with high-risk features. Although PSMA PET/CT is increasingly making its way into clinical practice around the world, Canadian provinces will need to make an informed decision of whether to fund this imaging for our patients. The high-level evidence gathered in this trial is desperately needed to assess the impact on patient outcomes and, in doing so, justify broad access and reimbursement for patients with prostate cancer.

Eligibility criteria: Inclusion Criteria:

* Histological diagnosis of adenocarcinoma of the prostate planned for curative-intent standard-of-care radiotherapy (primary or salvage post prostatectomy) or radical prostatectomy with lymph node dissection.
* Age ≥ 18
* High risk of regional or distant metastases as defined by any of:
* Newly diagnosed and untreated prostate cancer with CAPRA score 6-10, or stage cN1.
* Prior history of radical prostatectomy and biochemical failure (PSA\>0.1ng/mL).
* Patients must provide study-specific informed consent prior to study entry.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

Exclusion Criteria:

* Active or prior androgen deprivation therapy (except 5-alpha reductase inhibitor) terminated \< 12 months prior to enrollment.
* Prior or planned PSMA PET/CT scan outside of this clinical trial.
* Charlson Comorbidity Index \> 5 (see Appendix 2).
* Prior curative intent treatment for prostate cancer with local therapy other than surgery (primary radiotherapy or ablative therapies)
* Evidence of extra-pelvic nodal disease (M1a) on conventional imaging (if performed)
* Evidence of metastatic disease (M1b bone, M1c viscera/soft tissue) on conventional imaging (if performed)

Primary outcomes:
measure: To determine if PSMA PET/CT guided intensification of therapy is superior to standard of care (SOC) therapy as measured by improved failure-free survival (FFS).
timeFrame: 5 years
Secondary outcomes:
measure: Rates of toxicity (CTCAE)
timeFrame: 5 years
measure: Time to subsequent next-line therapy
timeFrame: 5 years
measure: Quality of Life (EPIC 26)
timeFrame: 5 years
measure: New lesion detection yield (on PSMA PET/CT)
timeFrame: 3 years
measure: Impact of PMSA PET/CT on RT or surgical management (rate of treatment intensification)
timeFrame: 3 years
measure: Cost-effectiveness (EQ5D5L)
timeFrame: 5 years
Other outcomes:
Locations:
city: Kelowna
country: Canada
facility: BC Cancer Kelowna
state: British Columbia
city: Vancouver
country: Canada
facility: BC Cancer Vancouver
state: British Columbia
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: Hamilton
country: Canada
facility: St-Joseph's Healthcare
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Kitchener
country: Canada
facility: Grand River Regional Cancer Centre
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Laval
country: Canada
facility: Hopital de la Cité de la Santé
state: Quebec
city: Montreal
country: Canada
facility: Charles Lemoyne Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Center
state: Quebec
city: Québec
country: Canada
facility: CHU de Québec
state: Quebec
city: Sherbrooke
country: Canada
facility: CHUS
state: Quebec
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
city: Edmonton
country: Canada
facility: Cross Cancer Institute
city: Montreal
country: Canada
facility: Jewish General Hospital
city: Montréal
country: Canada
facility: CHUM
city: Windsor
country: Canada
facility: Windsor Regional Cancer Centre
city: Winnipeg
country: Canada
facility: Cancer Care Manitoba
Study officials:
References:
citation: Menard C, Young S, Zukotynski K, Hamilton RJ, Benard F, Yip S, McCabe C, Saad F, Brundage M, Nitulescu R, Bauman G. PSMA PET/CT guided intensification of therapy in patients at risk of advanced prostate cancer (PATRON): a pragmatic phase III randomized controlled trial. BMC Cancer. 2022 Mar 8;22(1):251. doi: 10.1186/s12885-022-09283-z.