Four-Timepoint Multi-tracer PET Imaging to Characterize Metastatic prOstate Cancer Heterogeneity (4TMPO)

Imaging modalities currently used in the clinics do not image cancer, but the effect ofncancer on bone (bone scan) or on the anatomy (CT-scan). Bone scan and CT-scan are therefore named conventional imaging (CI) modalities. Positron Emission Tomography (PET) is an imaging technique that uses tracers to measure cancer activity in each lesion and is therefore quantitative. Usually, treatment changes in metastatic prostate cancers are based on the appearance of new lesions on CI, named metastases. Prostate cancer metastases have been shown to be clonal, which means that there are several cancers within each patient, potentially with divergent behaviors under therapy. In other words, some metastases might be resistant to a systemic therapy like chemotherapy, while others might be sensitive. The study proposes here to use molecular imaging by positron emission tomography to image and quantify the activity of prostate cancer cells in each metastasis before start, after 3 months and after progression during systemic therapy.

Each metastasis will then be measured to assess whether there is an increase (resistance) or a decrease (response) in prostate cancer cell activity. The analysis will determine how many metastases progress or remain stable when new metastases appear on conventional imaging (polyclonal resistance), as well as the impact of a change in therapy on metastases that were previously stable when cancer progressed elsewhere. In addition, the genes expressed in responding and non-responding metastases will be analyzed to identify gene expression patterns associated with resistance and/or response. Overall, this study aims to characterize metastatic prostate cancer clonal resistance mechanisms using serial PET molecular imaging and imaging-guided genomics.

Study Overview

• Status: Recruiting
• Conditions: mCRPC (Metastatic Castration-resistant Prostate Cancer)
• Intervention / Treatment: Diagnostic test: PET Tracer

Detailed Description

This is a multi-center, open-label, single-arm, non-randomized study using a multi-timepoint triple tracer molecular imaging to characterize intra-patient cancer phenotypes between metastases and to monitor phenotypic plasticity non-invasively. This will be done using 18F-FDG, 68Ga-PSMA (or any other PSMA tracer) and 68Ga-DOTATATE in participants progressing with CRPC and showing at least 3 metastases after conventional imaging. Any PSMA tracer could be used but the first PSMA-PET scan determines the PSMA radiotracer that will be used throughout the study, in order to make the analysis of the radiographic evolution of metastases more accurate (e.g. 68Ga-PSMA-617 or 18F-DCF-PyL or 68Ga-PSMA-11). The reference imaging must have been performed either: 1) after biochemical progression on treatment OR 2) at least 90 days after last treatment has begun if imaging was performed while patient was still responding (to avoid disappearance of metastasis due to treatment response). These imaging will include: 1) bone scan or 18F-Na-PET/CT AND either chest/abdomen CT or chest CT and abdomen MRI OR 2) 18F-FDG-PET/CT. This study is planned to be conducted in up to 4 sites in Canada. Eligible participants (see Section for Eligibility Criteria) will be enrolled in a non-randomized, sequential manner, with competitive enrollment between study sites. A total of 45 participants will be accrued. Enrolled participants will undergo 18F-FDG, 68Ga- or 18F-PSMA and 68Ga-DOTATATE-PET/CT scans. After initial triple tracer PET molecular imaging, the participants will be treated with cabazitaxel or docetaxel or ARPI (as standard of care or as an investigational agent) or PSMA-radioligand therapy (as standard of care or as an investigational agent). Three (3) months after initiation of systemic therapy double-tracer (PSMA & FDG) PET/CT imaging will be performed. Participants will continue their therapy and once progression will occur (V3, Progression 1), triple tracer will be repeated and a biopsy of a progressive lesion will be executed. Patients will be treated with a mandatory second line of approved mCRPC systemic therapies: PSMA-RLT therapy (Pluvicto 177Lu-PSMA-617) or Olaparib (PARPi) if they are found with homologous recombination repair (HRR) mutation (a predictive biomarker for PARPi). If not HRR mutated nor eligible to PSMA-RLT, a second line of approved mCRPC systemic therapy or research protocol will be offered. At Progression 2 (V4) (after treatment change following Progression 1), double-tracer 68Ga-PSMA and 18F-FDG PET/CT imaging will be repeated (DOTATATE scan will be optional). The patient will have another biopsy of a progressing lesion and an optional second biopsy of a non-progressing site offered.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marie-Christine Dubé, PhD; Phone Number: 67708 418-525-4444; Email: marie-christine.dube@crchudequebec.ulaval.ca

Study Locations

• Canada
  • Quebec
    • Québec, Quebec, Canada, G1J1Z4
      • Recruiting
      • CHU de Quebec-Universite Laval
      • Contact: Marie-Christine Dubé, PhD; Phone Number: 67708 418-525-4444; Email: marie-christine.dube@crchudequebec.ulaval.ca
      • Principal Investigator: Frédéric Pouliot, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Assign male at birth, any gender ≥ 18 years old;
2. Histologically or cytologically proven adenocarcinoma of the prostate;
3. Metastatic disease documented by at least 3 metastatic active lesions*, ** on whole body bone scan and/or measurable soft tissue on CT-scan (lymph nodes and visceral lesions);
4. CRPC & post-androgen receptor pathway inhibitor (ARPI) defined by progression under continuous castration (measured serum testosterone ≤50 ng/dL [1.73 nM]) AND an ARPI (darolutamide, apalutamide, enzalutamide or abiraterone acetate);

5. Eligible for taxane chemotherapy or PSMA-radioligand therapy (before imaging); 6-Able and willing to provide signed informed consent and to comply with protocol requirements.

   • Metastatic lesions on imaging are defined either: ≥ 10 mm on CT scan or caliper (for lymph nodes, see below), ≥ 20 mm on chest X-ray, lymph node ≥ 10 mm or having grown by ≥ 5 mm from baseline CT, any metastasis described on bone scan counts as a lesion. Of note: A bone lesion that has been treated by radiation is excluded from the lesions counted in the criterion of ≥ 3 lesions.

     • The reference imaging (scan with 3 metastases) confirming eligibility must be done either: 1) after biochemical progression on treatment OR 2) ≥ 90 days after last treatment has begun if imaging was performed while patient was still responding (to avoid disappearance of metastasis due to response).

Exclusion Criteria:

• 1. Another non-cutaneous malignancy or melanoma diagnosed in the past 5 years; 2. Currently under a randomized controlled trial with unknown allocation; 3-Any disease or condition limiting the patient's capacity to execute the study procedures, based on the investigators' opinion;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PET with FDG, PSMA and DOTATATE	Diagnostic test: PET Tracer; Multi-tracer PET imaging to characterize metastatic prOstate Cancer heterogeneity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the change in prevalence of IIH of mCRPC undergoing consecutive lines of systemic therapy.	Percentage of patients that show heterogeneous FDG and PSMA tracer uptakes between at least two metastases at baseline and at each progression following consecutive lines1 of study systemic therapies.	At Baseline and at the date of first and second documented progression, assessed up to 60 months
Determine intrapatient intermetastasis therapeutic heterogeneous response (IIHR) in mCRPC patients.	Percentage of patients that show opposite FDG and/or PSMA tracer uptake and/or ratio responses between two metastases after first and second study systemic therapy.	At the date of first and second documented progression, assessed up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the impact of systemic treatment change on progressing and non-progressing FDG or PSMA PET lesions under last treatment.	Percentage of metastases per patient that will show a significant increase or decrease of FDG or PSMA tracer uptake or ratio after subsequent treatment change for progression.	At the date of first and second documented progression, assessed up to 60 months
Correlate histopathology of biopsies to imaging phenotypes.	Associate histopathology and immunohistochemistry (IHC) with double tracer imaging phenotypes of biopsied patients.	At the date of first and second documented progression, assessed up to 60 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Link radiomic, and genomic features of single-timepoint and sequential multitracer PET imaging with clinical outcomes. Characterize the biological features of FDG positive/DOTATATE any/PSMA negative lesions (poor prognosis) vs PSMA positive/FDG any/DO	Molecular imaging parameters (including DOTATATE data) and genomics that will predict radiographic or clinical failure to systemic therapy from data at baseline, 3 months and at progression.; Molecular characterization of aggressive and less aggressive cancer by fresh frozen analysis (omics) and organoid cultures harvested from corresponding lesions.	At the date of randomization, then 3 months after randomizaton and at the date of first and second documented progression, assessed up to 60 months

Collaborators and Investigators

• Sponsor: Frederic Pouliot
• Investigators: Principal Investigator: Frédéric Pouliot, MD, PhD, CHU de Quebec-Universite Laval

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: November 17, 2025
• First Submitted That Met QC Criteria: December 11, 2025
• First Posted (Actual): December 24, 2025

Study Record Updates

• Last Update Posted (Actual): December 24, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: oncology; molecular imaging tracers
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 2025-7376

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No