## Protocol Section
### Identification Module
**NCT ID:** NCT03465579

**Acronym:** BIOPSTAGE

**Brief Title:** 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.

#### Organization Study ID Info
**ID:** IRST185.05
#### Organization
**Class:** OTHER
**Full Name:** Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
### Status Module
#### Completion Date
**Date:** 2024-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-06-01

**Type:** ACTUAL

**Last Update Submit Date:** 2023-05-31

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2018-05-23

**Type:** ACTUAL

**Status Verified Date:** 2023-05

#### Study First Post Date
**Date:** 2018-03-14
**Type:** ACTUAL
**Study First Submit Date:** 2018-03-08
**Study First Submit QC Date:** 2018-03-08
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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);

### Conditions Module

**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

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** DIAGNOSTIC

#### Enrollment Info

**Count:** 306

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Men with suspected clinically-significant PCa (CS-PCa) who are candidates for prostate biopsy or after first-round negative transrectal ultrasonography (TRUS) biopsy

**Intervention Names:**

- Diagnostic Test: pelvic MRI

- Diagnostic Test: 68Ga-PSMA PET/CT

**Label:** Cohort 1

**Type:** OTHER

#### Arm Group 2

**Description:** Men framed in Active Surveillance (PRIAS study), scheduled for PRIAS repeat biopsy.

**Intervention Names:**

- Diagnostic Test: pelvic MRI

- Diagnostic Test: 68Ga-PSMA PET/CT

**Label:** Cohort 2

**Type:** OTHER

#### Arm Group 3

**Description:** Men with high-risk PCa (HR-PCa) prior to radical surgery.

**Intervention Names:**

- Diagnostic Test: pelvic MRI

- Diagnostic Test: 68Ga-PSMA PET/CT

**Label:** Cohort 3a

**Type:** OTHER

#### Arm Group 4

**Description:** Men diagnosed with CS-PCa prior to nerve-sparing prostate surgery (NSS).

**Intervention Names:**

- Diagnostic Test: pelvic MRI

- Diagnostic Test: 68Ga-PSMA PET/CT

**Label:** Cohort 3b

**Type:** OTHER

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Cohort 1

- Cohort 2

- Cohort 3a

- Cohort 3b

**Description:** multi-parametric pelvic MRI

**Name:** pelvic MRI

**Type:** DIAGNOSTIC_TEST

#### Intervention 2

**Arm Group Labels:**

- Cohort 1

- Cohort 2

- Cohort 3a

- Cohort 3b

**Description:** 68Ga-PSMA PET/CT

**Name:** 68Ga-PSMA PET/CT

**Type:** DIAGNOSTIC_TEST

### Outcomes Module

#### Primary Outcomes

**Description:** sensitivity of both 68Ga-PSMA PET/CT and mp-3TMRI imaging will be calculated as the ratio between the number of positive cases at 68Ga-PSMA PET/CT or mp-3TMRI and number of patients who underwent to these exams

**Measure:** sensitivity of both 68Ga-PSMA PET/CT and mp-3TMRI imaging

**Time Frame:** up to 36 months

**Description:** specificity will be calculated considering negative cases at 68Ga-PSMA PET/CT or mp-3TMRI and number of patients who underwent to these exams

**Measure:** specificity of both 68Ga-PSMA PET/CT and mp-3TMRI imaging

**Time Frame:** up to 36 months

**Description:** Positive predictive value will be calculated considering the ratio between positive patient at 68Ga-PSMA PET/CT/mp-3TMRI confirmed as positive throughout biopsy and overall positive patient at 68Ga-PSMA PET/CT/mp-3TMRI

**Measure:** Positive predictive value of both 68Ga-PSMA PET/CT and mp-3TMRI imaging

**Time Frame:** up to 36 months

**Description:** negative predictive value will be calculated considering the ratio between negative patient at 68Ga-PSMA PET/CT/mp-3TMRI confirmed as negative throughout biopsy and overall negative patient at 68Ga-PSMA PET/CT/mp-3TMRI

**Measure:** negative predictive value of both 68Ga-PSMA PET/CT and mp-3TMRI imaging

**Time Frame:** up to 36 months

#### Secondary Outcomes

**Description:** The number and percentage of treated patients undergoing grade 1 to 4 adverse events will be tabulated for each cohort and diagnostic procedure, using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 should be used to assess and grade AE severity.

**Measure:** Incidence of adverse events

**Time Frame:** up to 30 days following study procedures

### Eligibility Module

**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.

**Minimum Age:** 18 Years

**Sex:** MALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** oriana.nanni@irst.emr.it

**Name:** Oriana Nanni

**Phone:** +390543739266

**Role:** CONTACT

**Contact 2:**

**Email:** federica.matteucci@irst.emr.it

**Name:** Federica Matteucci, MD

**Phone:** +390543739100

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Forlì

**Contacts:**

***Contact 1:***

- **Name:** Roberta Gunelli

- **Role:** CONTACT

**Country:** Italy

**Facility:** AUSL della Romagna

**State:** FC

**Status:** RECRUITING

**Zip:** 47121

**Location 2:**

**City:** Meldola

**Contacts:**

***Contact 1:***

- **Email:** federica.matteucci@irst.emr.it

- **Name:** Federica Matteucci, MD

- **Phone:** +390543739100

- **Role:** CONTACT

**Country:** Italy

**Facility:** Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)

**State:** FC

**Status:** RECRUITING

**Zip:** 47014

#### Overall Officials

**Official 1:**

**Affiliation:** IRST IRCCS

**Name:** Federica Matteucci

**Role:** STUDY_CHAIR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000005834

- Term: Genital Neoplasms, Male

- ID: D000014565

- Term: Urogenital Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000005832

- Term: Genital Diseases, Male

- ID: D000091662

- Term: Genital Diseases

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000011469

- Term: Prostatic Diseases

- ID: D000052801

- Term: Male Urogenital Diseases

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M14335

- Name: Prostatic Neoplasms

- Relevance: HIGH

- As Found: Prostate Cancer

- ID: M12307

- Name: Neoplasm Metastasis

- Relevance: LOW

- As Found: Unknown

- ID: M8946

- Name: Genital Neoplasms, Male

- Relevance: LOW

- As Found: Unknown

- ID: M17315

- Name: Urogenital Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M2876

- Name: Genital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8944

- Name: Genital Diseases, Male

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14333

- Name: Prostatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27095

- Name: Male Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000011471

- Term: Prostatic Neoplasms

- ID: D000004194

- Term: Disease

### Intervention Browse Module - Ancestors

- ID: D000019275

- Term: Radiopharmaceuticals

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M352637

- Name: Gallium 68 PSMA-11

- Relevance: HIGH

- As Found: Independent

- ID: M21258

- Name: Radiopharmaceuticals

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000718244

- Term: Gallium 68 PSMA-11

### Misc Info Module

- Version Holder: 2024-05-24
