3TMPO (Triple-Tracer Strategy Against Metastatic Prostate Cancer
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|ClinicalTrials.gov Identifier: NCT04000776|
Recruitment Status : Recruiting
First Posted : June 27, 2019
Last Update Posted : February 11, 2020
Prostate cancer (PCa) is the most common solid organ cancer in North American men. Patients becoming refractory to loco-regional therapy receive androgen deprivation therapy, but their disease will inevitably progress to metastatic castration-resistant prostate cancer (mCRPC). Treatment failure and poor progression-free survival could be explained by the fact that PCa metastases in the same patient may be polyclonal, showing opposite responses to systemic therapies.
This project aims to recruit 100 patients with mCRPC in order to determine the prevalence of intrapatient intermetastasis polyclonality and NED using PET/CT triple-tracer PSMA/FDG/OCTREOTATE imaging and eligibility for either PSMA or OCTREOTATE radioligand therapy (RLT).
|Condition or disease||Intervention/treatment|
|Metastatic Castration-resistant Prostate Cancer||Diagnostic Test: FDG Positron emission tomography (PET) scan Diagnostic Test: PSMA Positron emission tomography (PET) scan Diagnostic Test: OCTREOTATE Positron emission tomography (PET) scan Other: Optional Bone or soft-tissue biopsies|
Introduction: Prostate cancer (PCa) is the most common solid organ cancer in North American men. Patients becoming refractory to loco-regional therapy receive androgen deprivation therapy, but their disease will inevitably progress to metastatic castration-resistant prostate cancer (mCRPC). Of the five treatments approved for mCRPC patients, none has been shown to increase median overall survival beyond 4.8 months. Treatment failure and poor progression-free survival could be explained by the fact that PCa metastases in the same patient may be polyclonal, showing opposite responses to systemic therapies. Indeed, neuroendocrine differentiation from adenocarcinoma is often reported in metastatic PCa, which is associated with increased disease aggressiveness. Currently, no molecular tools are available to follow non-invasively mCRPC transdifferentiation and diagnose patients with neuroendocrine and/or polyclonal PCa. Positron emission tomography (PET) is a promising type of imaging using radio-labeled tracers to specifically identify tumour cells.
Hypothesis: The hypothesis of the 3TMPO clinical study is that the prevalence of intrapatient intermetastasis polyclonality can be diagnosed by combining 18F-FDG to other specific PET tracers that have the ability to non-invasively differentiate CRPC adenocarcinoma (CRPC-Adeno) (68Ga-PSMA) from neuroendocrine CRPC (CRPC-NE) tumours (68Ga-OCTREOTATE).
Objectives: The study objectives are to determine, in mCRPC patients, the prevalence of intrapatient intermetastasis polyclonality and NED using PET/CT triple tracer PSMA/FDG/OCTREOTATE imaging and their eligibility for radioligand therapy (RLT).
Method: This multicentre observational clinical study, for which prevalence of intrapatient intermetastasis polyclonality was set as the primary outcome, will recruit 100 mCRPC patients at 5 different sites across the province of Québec. 68Ga-PSMA and 18F-FDG PET scans will be performed on all enrolled patients, while 68Ga-OCTREOTATE will be performed on those presenting at least one PSMA-negative/FDG-positive lesion. The uptake of each individual lesion will be assessed for each PET tracer and patients with lesions presenting discordant uptake profiles will be considered as having polyclonal disease. OCTREOTATE-positivity will confirm the presence of CRPC-NE. PSMA or OCTREOTATE positivity of all lesions (or at least those with FDG uptake) will determine the eligibility for PSMA and OCTREOTATE RLT, respectively.
Relevance: Paradigm-shifting diagnostic and therapeutic strategies are urgently needed to improve the survival of patients with PCa and to deepen our understanding of mCRPC progression.
|Study Type :||Observational|
|Estimated Enrollment :||100 participants|
|Official Title:||Triple-tracer Molecular Imaging Using 18F-FDG, 68Ga-PSMA and 68Ga-OCTREOTATE to Characterize Metastatic Castration-resistant Prostate Cancer (mCRPC) and Evaluate Eligibility for Radionuclide Therapies|
|Actual Study Start Date :||December 16, 2019|
|Estimated Primary Completion Date :||September 2021|
|Estimated Study Completion Date :||September 2021|
- Diagnostic Test: FDG Positron emission tomography (PET) scan
Patients will undergo 18F-FDG and whole-body PET/CT (vertex to thighs, or to feet if known lower-limb metastases).
The patient will be measured and weighed before the exam in order to calculate a personalized dose. An intravenous catheter will be put in place in peripheral vein to allow injection of the tracer.
- Diagnostic Test: PSMA Positron emission tomography (PET) scan
Patients will sequentially undergo 68Ga-PSMA and whole-body PET/CT (vertex to thighs, or to feet if known lower-limb metastases).
- Diagnostic Test: OCTREOTATE Positron emission tomography (PET) scan
In the case a patient would present at least one PSMA-negative/FDG-positive lesion, he will be referred to undertake a whole-body 68Ga-OCTREOTATE PET/CT within 10 days of the first PET/CT. The delay between this third PET scan and the last one should be minimal (not least than 18 hours, not more than 10 days).
Images and data will be reviewed centrally within 4 days by the Imaging Corelab, which will produce a final report confirming patient's eligibility to Radioligand therapy (RLT).
- Other: Optional Bone or soft-tissue biopsies
Patients presenting FDG-positive/PSMA-negative or Octreotate-positive lesions on imaging will be asked to undergo a biopsy of these lesions (optional) for research purposes. Bone or soft-tissue biopsies will be collected by an interventional radiologist according to site's standard-of-care procedure and sent to the local pathology department for preparation (formalin-fixed and paraffin-embedded); the blocks being sent to the Pathology Corelab.
- Polyclonality [ Time Frame: Baseline ]POLYCLONALITY DEFINITION: A patient will be determined as having a polyclonal PCa disease when we will detect: (1) Both [PSMA-positive/FDG-positive or negative] and [PSMA-negative/FDG-positive] lesions OR; (2) Both [FDG-positive/PSMA-positive or negative] and [FDG-negative/PSMA-positive] lesions OR; (3) In patients with only PSMA-negative/FDG-positive lesions undergoing OCTREOTATE-PET, both OCTREOTATE-positive and OCTREOTATE-negative lesions.
- Neuroendocrine lesion [ Time Frame: Baseline ]Neuroendocrine lesion DEFINITION: A patient with at least one OCTREOTATE-positive lesion will be identified as having CRPC-NE disease (regardless of polyclonality).
- Eligible patients for PSMA-RLT or OCTREOTATE-RLT [ Time Frame: Baseline ]Eligibility for PSMA RLT is defined as : Having (1) at least one lesion that is PSMA-positive, and (2) no lesion that is PSMA-negative and FDG-positive. Eligibility for Octreotate RLT: Having (1) at least one lesion that is Octreotate-positive, and (2) no lesion that is Octreotate-negative and FDG-positive.
- 18F-FDG, 68Ga-PSMA and 68Ga-OCTREOTATE positive lesions [ Time Frame: Baseline ]POSITIVE LESION: 18F-FDG, 68Ga-PSMA and 68Ga-OCTREOTATE lesion uptake will be defined as positive if greater than that of the liver [18,19]. Using quantitative imaging methods, standardized uptake value ratio (SUVR, i.e. the ratio between lesion uptake (SUVpeak) over liver uptake (SUVmean)) will be obtained for each lesion with each tracer. For a given tracer, lesion positivity is defined as a SUVR equal or superior to 1.5.
- histologic NED status of lesions [ Time Frame: Baseline ]positive histology to synaptophysin
- Pain score [ Time Frame: Baseline and 3-months post-enrolment ]Using a Brief Pain Index (BPI) questionnaire. The severity can be expressed through 4 aspects: worst, least, average and now. The pain interference with daily activities can be represented with 7 aspects: general activity, walking, work, mood, enjoyment of life, relationships and sleep.
- Physical function [ Time Frame: Baseline and 3-months post-enrolment ]Using EQ5D questionnaire which use a 5-scale and evaluates 5 aspects: mobility, selfcare, activity, pain, anxiety and global self-evaluation.
- Disease-associated symptoms [ Time Frame: Baseline and 3-months post-enrolment ]using FACT-P questionnaire: with subscale specific for wellbeing on physical, social/family, emotional functional and prostate aspects.
- PET-tracer uptake derived parameters [ Time Frame: Baseline ]such as SUVmax, SUV mean, sum of SUVmax
Biospecimen Retention: Samples Without DNA
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): NCT04000776
|Contact: Amélie Têtu, MSc||819-346-1110 ext email@example.com|
|CHUM, Université de Montréal||Not yet recruiting|
|Montréal, Quebec, Canada, H2X0C1|
|Contact: Amal Nadiri 514-890-8000 ext 26074 firstname.lastname@example.org|
|McGill University Health Centre||Not yet recruiting|
|Montréal, Quebec, Canada, H4A3J1|
|Contact: Penny Chipman 514-934-1934 ext 64802 email@example.com|
|CIUSSS du Centre-Ouest-de -l'île-de-Montreal (CIUSSS-COMTL)||Not yet recruiting|
|Montréal, Quebec, Canada|
|Contact: Aline Mamo 514-340-8222 ext 24146 Aline.Mamo@ladydavis.ca|
|CHU de Québec - Université Laval (CRCHUQc-UL),||Recruiting|
|Québec, Quebec, Canada, G1R 3S1|
|Contact: Guillaume Bouvet firstname.lastname@example.org|
|Centre de recherche du CHUS (CRCHUS), Division of Urology, CIUSSS de l'Estrie - CHUS (CIUSSSE-CHUS)||Recruiting|
|Sherbrooke, Quebec, Canada, J1H5N4|
|Contact: Elsie Morneau, BSN 819-346-1110 ext 12827 email@example.com|
|Principal Investigator:||Brigitte Guérin, Ph.D||Department of Nuclear Medicine,Université de Sherbrooke|