Clinical trial NCT04000776: 3TMPO (Triple-Tracer Strategy Against Metastatic Prostate Cancer
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Metastatic Castration-resistant Prostate Cancer
Lead sponsor: Université de Sherbrooke
Sponsor class: OTHER
Collaborators: name: Fonds de la Recherche en Santé du Québec
name: Oncopole
name: Canadian Cancer Society (CCS)
name: Merck Canada Inc.
First posted: 2019-06-27
Enrollment: 100
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 100 patients will be enrolled in five tertiary hospital centers (CIUSSSE-CHUS, CHUQc-UL, CHUM, CIUSSS-COMTL, and MUHC) of the province of Quebec

Brief 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.

Eligibility criteria: Inclusion Criteria:

1. Male ≥ 18 years old
2. Histologically or cytologically proven PCa with or without neuroendocrine differentiation at initial diagnosis
3. Castration-resistant prostate cancer with serum testosterone ≤ 50 ng/dL (1.73 nM) anytime while on androgen deprivation therapy
4. Evidence of disease progression on prior therapy or watchful waiting. Disease progression is defined by meeting at least one of the following criteria:

   1. PSA progression defined by a minimum of 2 consecutive rising PSA levels with an interval of ≥1 week between each assessment where the PSA value at screening should be ≥1ng/ml.
   2. Soft tissue disease ONLY progression\* defined by RECIST 1.1: 1) at least 20% increase in the diameter of target lesions and 2) an absolute increase of ≥ 5 mm of the sum.
   3. Soft tissue disease ONLY progression\* defined as the appearance of at least one new lesion (soft tissue).
   4. Bone disease ONLY progression\* defined by two or more new lesions on bone scan.
5. Metastatic disease documented by at least 3 active lesions on whole body bone scan and/or measurable soft tissue on CT-scan (lymph nodes and visceral lesions). Metastatic lesions on imaging are defined by RECIST 1.1, either:

   * ≥ 10 mm on CT scan or caliper (for lymph nodes, see below)
   * ≥ 20 mm on chest X-ray
   * lymph node ≥ 15 mm or ≥ 10 mm and having grown by ≥ 5 mm from baseline CT
   * any metastasis described on bone scan counts as a lesion
6. Able and willing to provide signed informed consent in French or English and to comply with protocol requirements.

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. Limited survival prognosis (ECOG ≥3);
4. Patients under dialysis;
5. Any disease or condition limiting the patient's capacity to execute the study procedures, based on the investigators' opinion.

Primary outcomes:
measure: Prevalence of INTRAPATIENT INTERMETASTATIC HETEROGENEITY
timeFrame: Baseline
measure: Proportion of neuroendocrine lesion
timeFrame: Baseline
measure: Proportion of eligible patients for PSMA-RLT or OCTREOTATE-RLT
timeFrame: Baseline
Secondary outcomes:
measure: 18F-FDG, 68Ga-PSMA and 68Ga-OCTREOTATE positive lesions
timeFrame: Baseline
measure: histologic NED status of lesions
timeFrame: Baseline
measure: Pain score
timeFrame: Baseline and 3-months post-enrolment
measure: Physical function
timeFrame: Baseline and 3-months post-enrolment
measure: Disease-associated symptoms
timeFrame: Baseline and 3-months post-enrolment
measure: PET-tracer uptake derived parameters
timeFrame: Baseline
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: CHUM, Université de Montréal
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Montréal
country: Canada
facility: CIUSSS du Centre-Ouest-de -l'île-de-Montreal (CIUSSS-COMTL)
state: Quebec
city: Québec
country: Canada
facility: CHU de Québec - Université Laval (CRCHUQc-UL),
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre de recherche du CHUS (CRCHUS), Division of Urology, CIUSSS de l'Estrie - CHUS (CIUSSSE-CHUS)
state: Quebec
Study officials:
affiliation: Department of Nuclear Medicine,Université de Sherbrooke
name: Brigitte Guérin, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: