Radio Guided Lymph Node Dissection in Oligometastatic Prostate Cancer Patients (DETECT)

The study is a prospective, single arm phase I/II study. The primary aim of this study is to evaluate the feasibility of 111In-PSMA I&T radio guided surgery in patients diagnosed with prostate cancer who are highly suspected of having one or more pelvic lymph node metastases based on pre-operative imaging.

Patients with prostate cancer who have a high risk of lymph node metastases based on PSMA PET/CT and scheduled for robot-assisted PLND (with or without prostatectomy) will be recruited. Eligible patients will receive an additional ferumoxtran-10 enhanced MRI to complement pre-operative imaging. Twenty-four hours before surgery, patients will receive the radiolabelled PSMA tracer. Pelvic Lymph node dissections are carried out according to standard of care procedures. During surgery, the surgeon will be provided with a gamma-probe to detect PSMA expressing lymph nodes in vivo. Dissected samples will be systematically assessed on tracer accumulation using the gamma-probe ex vivo. After surgery, the samples will be scanned in the small animal SPECT/CT and 7T-MRI. After scanning, samples will be presented to pathologists for pathological analysis according to standard of care including staining for PSMA expression. At 3 months after surgery, patients will undergo a PSMA-PET/CT. Up until one year after surgery patients will be followed according to standard of care-guidelines by 3-monthly serum-PSA measurements.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer; Lymph Node Metastases
• Intervention / Treatment: Procedure: Radio guided surgery (RGS) using Indium-labelled PSMA

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Canisius Wilhelimina Ziekenhuis
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525
      • Radboudumc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Histologically proven cancer of the prostate, based on prostate biopsy-core analysis.
• At least one 18F/68Ga-PSMA-PET/CT suspected positive metastasis in lymph nodes, located in the pelvic region.
• Patient is scheduled and fit for robot assisted surgery (PLND or radical prostatectomy +PLND).
• Patient is suitable for PLND (and radical prostatectomy) conform institutional guidelines and is not yet treated pre-operatively .
• Age≥50 years.
• Ability to give voluntary written informed consent to participate in this study.

Exclusion Criteria:

• No detectable lesion on the 18F/68Ga-PSMA-PET/CT with an uptake level above liver uptake level (reference).
• Patients who are not scheduled for robot-assisted PLND.
• Prior pelvic surgery(1)
• Unequivocal evidence of metastases outside the pelvic region.
• Presence of any medical condition that in the opinion of the investigator/treating physician will affect patients' clinical status by participating in this trial.
• Prior prostate cancer treatment(2).
• Contraindication for MRI-scanning, i.e. claustrophobia, intracranial metal clips, metallic bodies in the eye, implanted electric and electronic devices not eligible for MRI (pacemakers, insulin pumps, cochlear implants, neurostimulators).
• Inability to lie still for at least 60 minutes or comply with imaging.
• Contraindication for iron infusion or hypersensitivity/allergy to the active substance or any of the excipients.

• The patient is already enrolled in one or more concurrent studies, which could confound the results of this study, according to the investigators.

  1. Pelvic surgery is defined as "any surgery associated with pelvic lymphadenopathy'.
  2. Prior prostate cancer treatment is defined as prostate and/or pelvic radiotherapy, hormonal treatments such as androgen deprivation therapy, prostate brachytherapy, prostate cryotherapy, high intensity focused ultrasound (HIFU) and/or prostate electroporation.

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: All patients; Intervention: radio guided surgery	Procedure: Radio guided surgery (RGS) using Indium-labelled PSMA; Approximately 24hours prior to surgery (PLND) patients receive a radiolabelled PSMA-tracer. During surgery, urologists will use a gamma-probe to detect PSMA-postitive tumour depostitions in pelvic lymph nodes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of 111In-PSMA-I&T radio guided surgery	The primary aim of this study is to evaluate the feasibility of 111In-PSMA-I&T radio guided surgery in patients diagnosed with prostate cancer who are highly suspected of having one or more pelvic lymph node metastasis/metastases based on pre-operative imaging. Feasibility will be defined as the ability to intra-operatively detect the lymph nodes (using a gamma probe) which were pre-operatively identified on PSMA-PET/CT	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The accuracy of 111In-PSMA-I&T radio guided surgery	Accuracy will be expressed as sensitivity and specificity percentage. Test results of gamma probe (positive or negative) will be compared with histopathology (gold standard) (positive or negative: i.e. containing PSMA-expressing prostate cancer cells).	1 year
The safety of 111In-PSMA-I&T	Safety will be assesed by the number of participants with treatment related adverse events as assessed by CTCAE v4.0. For this outcome measure extra bloodsampling is included in the study protocol.	1 year
Dosimetry of 111In-PSMA-I&T	Blood-clearance ratios will be determined based on radiation dosimetry as assessed by bloodsampling at set time points after injection.	1 year
Correlation between tracer accumulation and lymph node size, PSMA-staining and SUV on PSMA-PET/CT		1 year
Correlation between post-operative nano-MRI and SPECT		1 year
Correlation between pre-operative imaging and postoperative imaging		2 years

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: Michiel Sedelaar, MD, PhD, Radboudumc Nijmegen

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): April 1, 2023

Study Registration Dates

• First Submitted: February 17, 2020
• First Submitted That Met QC Criteria: March 6, 2020
• First Posted (Actual): March 9, 2020

Study Record Updates

• Last Update Posted (Actual): April 29, 2022
• Last Update Submitted That Met QC Criteria: April 27, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: pelvic lymph node dissection (PLND); PSMA I&T; radio guided surgery (RGS)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Neoplastic Processes; Neoplasm Metastasis; Prostatic Neoplasms; Lymphatic Metastasis
• Other Study ID Numbers: 2019-5805; 2019-003284-21 (EudraCT Number)

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