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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
Sponsor:
Collaborators:
Fonds de la Recherche en Santé du Québec
Oncopole
Canadian Cancer Society Research Institute (CCSRI)
Merck Canada Inc.
Information provided by (Responsible Party):
Université de Sherbrooke

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).


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

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.

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer


Intervention Details:
  • 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.


Primary Outcome Measures :
  1. 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.

  2. 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).

  3. 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.


Secondary Outcome Measures :
  1. 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.

  2. histologic NED status of lesions [ Time Frame: Baseline ]
    positive histology to synaptophysin

  3. 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.

  4. 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.

  5. 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.

  6. PET-tracer uptake derived parameters [ Time Frame: Baseline ]
    such as SUVmax, SUV mean, sum of SUVmax


Biospecimen Retention:   Samples Without DNA
Bone or soft-tissues biopsies


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
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) within 6 months prior screening
  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: 1) a PSA increase from baseline (beyond 12 weeks from last treatment onset), 2) with a minimal starting value of 1.0 ng/mL and 3) the increase in PSA beyond 1.0 ng/mL is at least 25 % from the baseline value and 1 week apart from the baseline PSA.
    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 metastatic lesions on whole body bone scan and/or soft tissue (lymph nodes and visceral lesions). Metastatic lesions 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 Of note: A bone lesion that has been radiated is excluded from the target lesions counted in the criterion of at least 3 lesions.
  6. On enrollment, patients must have been on the same therapy (or watchful waiting) as that on baseline imaging (reference scan with 3 metastases) confirming eligibility
  7. 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 RCT 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.

Information from the National Library of Medicine

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


Contacts
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Contact: Amélie Têtu, MSc 819-346-1110 ext 15571 amelie.tetu.ciussse-chus@ssss.gouv.qc.ca

Locations
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Canada, Quebec
CHUM, Université de Montréal Not yet recruiting
Montréal, Quebec, Canada, H2X0C1
Contact: Amal Nadiri    514-890-8000 ext 26074    amal.nadiri.chum@ssss.gouv.qc.ca   
McGill University Health Centre Not yet recruiting
Montréal, Quebec, Canada, H4A3J1
Contact: Penny Chipman    514-934-1934 ext 64802    penny.chipman@muhc.mcgill.ca   
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       guillaume.bouvet@crchudequebec.ulaval.ca   
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    elsie.morneau.ciussse-chus@ssss.gouv.qc.ca   
Sponsors and Collaborators
Université de Sherbrooke
Fonds de la Recherche en Santé du Québec
Oncopole
Canadian Cancer Society Research Institute (CCSRI)
Merck Canada Inc.
Investigators
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Principal Investigator: Brigitte Guérin, Ph.D Department of Nuclear Medicine,Université de Sherbrooke

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Responsible Party: Université de Sherbrooke
ClinicalTrials.gov Identifier: NCT04000776    
Other Study ID Numbers: 3TMPO
First Posted: June 27, 2019    Key Record Dates
Last Update Posted: February 11, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases