Clinical trial NCT03465579: Mp-3TMRI and 68Ga-PSMA PET/CT Guided Prostate Biopsy and Tumor Node Metastasis (TNM) Staging.
Official title: Multi-cohort Investigational Study to Evaluate the Impact of Pelvic Mp-3TMRI and Whole-body 68Ga-PSMA PET/CT for Diagnosis of Clinically-significant Prostate Cancer and Pre-surgical Staging.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: 68Ga-PSMA PET/CT Guided Prostate Biopsy
Mp-3TMRI Guided Prostate Biopsy
Prostate Cancer
TNM Staging
Diagnosis
Keywords: Diagnosis Prostate Cancer
TNM staging
68Ga-PSMA PET/CT guided prostate biopsy
mp-3TMRI guided prostate biopsy
pre-surgical staging
clinically-suspected prostate cancer
Lead sponsor: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
Sponsor class: OTHER
First posted: 2018-03-14
Enrollment: 261
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: BIOPSTAGE is a prospective, non-randomized, diagnostic, multi-cohort investigational study to evaluate the impact of pelvic Multi-parametric 3-Tesla magnetic resonance imaging (mp-3TMRI) and whole-body 68Ga-PSMA PET/CT for diagnosis of clinically-significant prostate cancer and pre-surgical staging.

Detailed description: The aim of this study is to characterize the diagnostic accuracy of both multi-parametric pelvic Magnetic Resonance Imaging (MRI) (T2-weighted, Diffusion Weighted Imaging (DWI), Dynamic Contrast Enhancement (DCE) and 68Ga-chelated Prostate Specific Membrane Antigen ligand (68Ga-PSMA) Positron Emission Tomography/Computed Tomography (PET /CT) in three cohorts of patients:

* COHORT 1 Guiding prostate biopsies in men with clinical suspicion and/or unconfirmed clinically-significant prostate cancer (CS-PCa) on initial prostate biopsy;
* COHORT 2 Targeting repeat prostate biopsy in patients on Active Surveillance (PRIAS Study), scheduled for PRIAS repeat biopsy;
* COHORT 3

Providing pelvic / whole-body pre-surgical staging in:

* 3a: men with high-risk PCa (HR-PCa);
* 3b: men candidates for nerve sparing surgery (NSS);

Eligibility criteria: Inclusion Criteria:

Cohort 1 - Biopsy guidance in clinically-suspected PCa

1. Men aged 45 to 75 years old with clinically-suspected PCa candidated for either initial or repeat TRUS-guided prostate biopsy, meeting any of the following criteria:

a) Abnormal PSA metrics, defined as follows:

A rising and/or persistently elevated serum PSA (i.e PSA \> 2.5ng/ml for men in the age group comprising 60 to 75 years old; PSA \> 3.0ng/ml for men in the age group comprising 45 to 60 years old) and at least one of the following PSA-based metrics:

i. Percent free PSA (%fPSA) \< 25% with PSA range 4-10ng/ml (NCCN); ii. PSA velocity (PSAvel) \>0.35 ng/mL/y; iii. PSA density (PSAden) \> 0.25ng/mL/cc iv. PSA \> 10ng/ml, 50% risk of PCa (EAU) b) Suspicious digital rectal examination (DRE), 5-30% risk of PCa; c) Prostate Cancer Gene 3 (PCA3) \> 35; d) Suspicious findings on first-round biopsy: i. A few Atypical Glands immediately adjacent to HG-PIN, 50% risk of PCa; ii. Atypical Small Acinar Proliferation, 40% of PCa; iii. Multifocal High-Grade Prostatic intraepithelial neoplasia (HG-PIN), 30% ; iv. Intraductal carcinoma as solitary finding, 90% of PCa;

Cohort 2 - Biopsy guidance on Active Surveillance

Men consenting to enter the PRIAS MRI side-study as per currently inclusion criteria in Version Number 1.0 dated August 20, 2013. These are:

1. Histologically-proven adenocarcinoma of the prostate;
2. Age ≥ 18
3. Men should be fit for curative treatment;
4. Clinical stage T1c or T2;
5. Gleason score 3+3=6;
6. One or two biopsy cores invaded with prostate cancer:

   1. If an MRI, including targeted biopsies on positive lesions, is done at inclusion, there is no limit in the number of positive cores (that is, more than two, and no limit in the % of cancer present in the cores);
   2. If saturation biopsies (either trans-perineal or trans-rectal) are done 15% of the cores can be positive with a maximum of 4 (i.e. 26 cores 4 cores can be positive) (all other inclusion criteria still apply);
7. PSA density (PSA D) less than 0.2;
8. PSA-level at diagnosis ≤ 10 ng/mL;

Cohort 3a - Pre-surgical TNM staging in high-risk prostate cancer

1. Male, aged 18 years or older;
2. Cyto / histological confirmation of PCa (i.e. TRUS-guided biopsies; TURP);
3. Any of the PCa high risk features for Organ-Confined Disease (OCD):

   * Clinical T stage ≥ T2c;
   * Gleason Score ≥ 8;
   * Serum PSA \> 20 ng/mL;
4. Any of the PCa high-risk features for Locally-Advanced Disease (LAD):

   * Clinical T stage ≥ T3b-T4 OR any T and clinical N1 disease;
   * Gleason Score ≥ 8;
   * Serum PSA \> 20 ng/mL;
5. Routine clinical staging (CTscan ± Bone scan) performed within 12 weeks enrolment returning negative or equivocal results for distant metastatic disease;

Cohort 3b - pelvic TNM staging of prostate cancer prior to nerve-sparing radical prostatectomy

1. Male, aged 18 years or older;
2. Cyto / histological confirmation of PCa (i.e. TRUS-guided biopsies; TURP);
3. All of the following PCa-related features must be met for nerve-sparing (either mono- or bi-lateral):

   * Clinical T stage ≤ T2b;
   * Gleason Score ≤ 7 (3+4) and maximum one biopsy with Gleason \> 6 at the ipsilateral side;
   * Serum PSA \< 10 ng/mL;

Exclusion Criteria:

The participant may not enter the study if ANY of the following apply:

1. Hormone androgen deprivation therapy of any type within 6 months prior to enrollment.
2. Prior pelvic radiotherapy;
3. Sickle cell disease;
4. Insufficient renal function (eGFR \< 30 mL/min/1.73 m2);
5. Hip prosthesis, vascular grafting or other conditions affecting imaging;
6. Contraindication to MRI, including but not restricted to: pacemaker or other electronic im-plants, known metal in the orbit, MR incompatible surgical or cerebral aneurysm clips, shrapnel, tattoos, non-removable body piercings (relative contraindications);
7. History of allergic reactions attributed to compounds of similar chemical or biologic com-position to 68Ga-PSMA or Gadolinium-based contrast agents used in the study.

Primary outcomes:
measure: sensitivity of both 68Ga-PSMA PET/CT and mp-3TMRI imaging
timeFrame: up to 36 months
measure: specificity of both 68Ga-PSMA PET/CT and mp-3TMRI imaging
timeFrame: up to 36 months
measure: Positive predictive value of both 68Ga-PSMA PET/CT and mp-3TMRI imaging
timeFrame: up to 36 months
measure: negative predictive value of both 68Ga-PSMA PET/CT and mp-3TMRI imaging
timeFrame: up to 36 months
Secondary outcomes:
measure: Incidence of adverse events
timeFrame: up to 30 days following study procedures
Other outcomes:
Locations:
city: Forlì
country: Italy
facility: AUSL della Romagna
state: FC
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)
state: FC
Study officials:
affiliation: IRST IRCCS
name: Federica Matteucci
role: STUDY_CHAIR
References: