Clinical trial NCT03160794: Prostate Cancer Subclinical Metastatic Ablative MR-guided Radiotherapy
Official title: Phase II Study: [18F]DCFPyL PET/MRI for Personalizing Prostate Cancer Subclinical Metastatic Ablative MR-guided Radiotherapy (MRgRT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Post Prostatectomy
Keywords: Prostate cancer
stereotactic ablative radiotherpy
PET/MR
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2017-05-19
Enrollment: 100
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: In the clinical scenario of recurrent prostate cancer (PCa) post local therapy, current standard studies (bone scan and computed tomography) commonly fail to identify the recurrent disease location. In this study the investigator aims to prospectively map recurrent disease with the unique combination of whole-body MR anatomical imaging combined with a new high-sensitivity and PCa-specific PET probe (PSMA-targeted: \[18F\]DCFPyL) to provide precise localization information to target disseminated tumor deposits in men presenting with rising PSA after prostatectomy and radiotherapy (maximal local therapies). Moreover, we will consequently treat all identified disease with image-guided stereotactic ablative radiotherapy (SABR), which has shown tantalizing results achieving excellent tumor eradication rates with minimal toxicities. This study is uniquely positioned to enable the discovery of new biomarkers and the correlation of prognostic tests (e.g. genomic signatures) from the initial prostatectomy specimen with the PET-MR/CT imaging results and curative-intent treatment outcomes.

The significance of the proposed work towards a measurable impact in PCa care is important to emphasize. The study team believes this novel curative-intent approach will transform lives, as opposed to therapies that transiently impact incurable disease stages. Herein, the focus is on patients at the earliest point of the disease spectrum of recurrent PCa after curative-intent treatments. Our hypothesis is that PSMA-targeted \[18F\]DCFPyL PET-MR/CT allows earlier detection and localization of defined metastatic targets in these patients, at a stage amenable to image-guided curative-intent therapy.


Eligibility criteria: * ECOG performance status of 0-2
* Absence of significant comorbidities rendering patient nor suitable for curative ablative approaches
* No history of non-skin malignancy
* Histological evidence of prostate adenocarcinoma on previous radical prostatectomy.
* No use of any form of hormonal therapy in the previous 12 months, or intention to start HT at time of enrollment.
* Normal serum testosterone level ascertained within 4-6 weeks of enrollment
* Absence of known metastatic disease
* Radiological studies without evidence of regional or distant metastases: CT abdomen-pelvis and bone scan within previous 3 months
* Able to lie supine at least 60 minutes to comply with imaging and treatment.
* Absence of impaired renal function (calculated GFR \> 30mL/min)
* Absence of sickle cell disease or other hemoglobinopathies
* No other medical conditions deemed by the PI to make patient ineligible for PET/MR scanning or SABR

No contraindications to MRI:

* Subject must weigh \<136kg (scanner weight limit)
* Subject must not have pacemakers, cerebral aneurysm clips, shrapnel injury, or implantable electronic devices not compatible with MRI
* Prior anaphylactic reaction to gadolinium

Rising PSA after maximal local therapies (radical prostatectomy and either adjuvant or salvage radiotherapy):

* Three documented PSA rises, at least 1 month apart from post radiotherapy.
* PSA value \>0.1 and \< 3 ng/mL, within 4-6 weeks of enrollment
* No use of any forms of ADT in the previous 12 months nor contemplated to be used at time of study enrollment. Salvage ADT to be started when PSA reaches a value of 6.0ng/ml or greater.

Primary outcomes:
measure: To determine if [18F]DCFPyL PET-MR/CT can identify early oligometastatic disease in patients with a rising PSA and negative staging (CS and BS) after standard-of-care maximal local therapies.
timeFrame: 3 years
measure: To determine if treating PET-MR/CT identified lesions with curative-intent treatment (e.g. stereotactic body radiation therapy or surgery) associated with favorable preliminary measures of clinical performance.
timeFrame: 3 Years
Secondary outcomes:
measure: Correlation between PSA kinetics and PET imaging parameters
timeFrame: 6 months post SABR
measure: Correlate between tissue biomarker and distant disease
timeFrame: 3 years
Other outcomes:
measure: [18F]DCFPyL PET/MR and PET/CT comparison
timeFrame: 3 years
measure: Concordance of PET-MR/CT finding and histological confirmation of metastatic foci.
timeFrame: 3 years
measure: Biomarker correlates
timeFrame: 3 years
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Princess Margaret Cancer Centre - University Health Network
name: Alejandro Berlin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Glicksman RM, Metser U, Valliant J, Chung PW, Fleshner NE, Bristow RG, Green D, Finelli A, Hamilton R, Stanescu T, Hussey D, Catton C, Gospodarowicz M, Warde P, Bayley A, Breen S, Vines D, Jaffray DA, Berlin A. [18F]DCFPyL PET-MRI/CT for unveiling a molecularly defined oligorecurrent prostate cancer state amenable for curative-intent ablative therapy: study protocol for a phase II trial. BMJ Open. 2020 Apr 22;10(4):e035959. doi: 10.1136/bmjopen-2019-035959.