NCT04000776

3TMPO (Triple-Tracer Strategy Against Metastatic Prostate Cancer

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

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 100 (actual)
• Sponsor: Université de Sherbrooke · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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).

Detailed description

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.

Conditions

• Metastatic Castration-resistant Prostate Cancer

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2019-12-16
• Primary completion: 2023-03-30
• Completion: 2023-06-30
• First posted: 2019-06-27
• Last updated: 2023-08-28

Locations

5 sites across 1 country: Canada