Tracer-Guided Surgery for Recurrent Prostate Cancer (Trace-II)

Tracer-Based Image Guided Surgery for Recurrent Prostate Cancer: A Prospective Randomized Controlled Trial

ADT with or without robot-assisted PSMA-radioguided surgery for patients with recurrent prostate cancer.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: ADT; Procedure: PSMA-radioguided surgery

Detailed Description

Improving the oncological treatment outcomes in men with a biochemical recurrence after primary prostate cancer (PC) treatment that are diagnosed with a disease recurrence confined to the regional lymph nodes or local residual disease using Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography and Computed Tomography (PET/CT.)

The proposed trial randomizes patients with recurrent PC following primary PC treatment to either 6 months of ADT or Technetium-PSMA-radioguided salvage surgery plus 6 months of ADT. Although the optimal duration of ADT is unknown, a minimal duration of 6 months of ADT seems advisable in this setting and will be mandatory for both arms.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Pim van Leeuwen, MD, PhD; Phone Number: 003125129111; Email: pj.v.leeuwen@nki.nl
• Study Contact Backup: Name: Lotte Zuur, MD; Phone Number: 003125129111; Email: l.zuur@nki.nl

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1066CX
      • Recruiting
      • Antoni van Leeuwenhoek Hospital
      • Contact: Pim van Leeuwen, MD/PhD; Phone Number: 020 512 9111; Email: pj.v.leeuwen@nki.nl
      • Contact: Lotte Zuur, MD; Phone Number: 020 512 9111; Email: l.g.zuur@nki.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male, aged ≥ 18 years.
• Hormone-sensitive recurrent prostate cancer after radical prostatectomy, external beam radiotherapy or brachytherapy
• ≤ 2 lymph node metastases or local residual disease within the pelvis with sufficient PSMA expression (≥2 times regional vascular activity level) as determined by PSMA-based PET
• PSA-value < 4 ng/mL in case of a local recurrence and PSA < 3 ng/ml in case of (a) nodal recurrence(s)
• Had a PSMA PET/CT within 90 days before surgery
• Suitable for salvage surgery, as per institutional guidelines.
• Charlson Comorbidity Index ≤ 4
• World Health Organisation (WHO) performance status 0, 1, or 2.
• Written and signed informed consent.

Exclusion Criteria:

• Other diagnosis of malignancy or evidence of other malignancy within 5 years before screening for this study (except non-melanoma skin cancer).
• More than 2 lymph node metastases on PSMA PET/CT
• Suspicion of local recurrent prostate cancer within the prostatic fossa not treatable by surgery
• Non-regional lymphadenopathy (cM1a) or distant metastases (cM1b/c) as assessed by preoperative PSMA PET/CT.
• Castration resistance defined by clinical or biochemical progression despite a combined androgen blockade
• Known contraindications to hormone therapy, according to standard recommendations in force
• Patient with a psychological, familial, sociological or geographical situation potentially hampering compliance with the study protocol and follow-up schedule
• Ongoing androgen deprivation therapy (ADT) or within 6 months prior to surgery.
• Severe claustrophobia interfering with PET/CT scanning.
• Absence or withdrawal of an informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A: ADT; Patients in arm A will receive standard 6 months of ADT according to current clinical guidelines.	Drug: ADT; Standard 6 months of ADT according to current clinical guidelines. ADT consists of one subcutaneous depot of 22,5mg triptorelin (Pamorelin), with 4 weeks bicalutamide 50mg per os from 2 weeks before till 2 weeks after the first Pamorelin administration.
Experimental: Arm B: ADT + PSMA radioguided surgery; Patients in arm B will receive standard 6 months of ADT according to current clinical guidelines, and will undergo 99mTechnetium (99mTc)-based PSMA-radioguided salvage surgery.	Drug: ADT; Standard 6 months of ADT according to current clinical guidelines. ADT consists of one subcutaneous depot of 22,5mg triptorelin (Pamorelin), with 4 weeks bicalutamide 50mg per os from 2 weeks before till 2 weeks after the first Pamorelin administration.; Procedure: PSMA-radioguided surgery; Approximately 15-24 hours prior to surgery, 400-600 Megabecquerel (MBq) of 99mTc-PSMA-I&S will be intravenously administered to the patient at the Nuclear Medicine department. Following this injection patients will be allowed to return home, and then present for their 99mTechnetium (99mTc)-based PSMA-radioguided salvage surgery the next day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical progression-free survival (CPFS)	CPFS is defined as time between randomization and the appearance of a recurrence (any N1 or M1) as suggested by PSMA PET/CT or symptoms related to progressive PC, or death due to any cause	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metastasis-free survival (MFS)	Metastasis-free survival will be defined as the time between randomization and the appearance of a metastatic recurrence (any M1) as suggested by PSMA PET-CT.	24 months
Biochemical progression-free survival (BPFS)	Biochemical progression-free survival will be defined as the time between randomization and the development of biochemical progression ( three consecutive rises in prostate specific antigen (PSA) 1 week apart, resulting in two 50% increases over the nadir and PSA>2 ng/ml)	24 months
Castrate resistant prostate cancer (CRPC)	CRPC is defined as castrate serum testosterone<50 ng/dl plus biochemical progression, i.e., three consecutive rises in PSA 1 week apart, resulting in two 50% increases over the nadir and PSA>2 ng/ml.	10 years
Overall survival (OS)	Overall survival will be read as the time from trial randomization to the date of death from any cause	10 years
Incidence of adjuvant therapy	ADT, radiation therapy or additional salvage surgery	10 years
Patient reported QOL as per EORTC-QLQ C30	Quality of life (QoL) will be assessed with the EORTC Core Quality of Life questionnaire's (QLQ-C30) global QoL scale ranging from 0 to 100, higher scores indicate better QoL	24 months
Patient reported QOL as per Expanded Prostate cancer Index Composite (EPIC) 26	Quality of life (QoL) will be assessed with the EPIC 26 questionnaire, containing 26 items covering 5 domains: Urinary Incontinence, Urinary Irritative/Obstructive, Bowel, Sexual, and Hormonal. Response options for each EPIC item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better QOL.	24 months
Complications	Assessment of 99mTc-PSMA-I&S injection-related as well as surgery-related complication rate according to Clavien-Dindo.	30 and 90 days
Number of in-field recurrences	Recurrence measured by use of PSMA PET/CT in the template of 99mTc-PSMA-radioguided surgery (RGS) supported salvage surgery	24 months
Specificity of 99mTc-PSMA RGS for salvage surgery for recurrent PC compared to histologic evaluation	In percentage	30 days
Sensitivity of 99mTc-PSMA RGS for salvage surgery for recurrent PC compared to histologic evaluation	In percentage	30 days
Positive Predictive Value of 99mTc-PSMA RGS for salvage surgery for recurrent PC compared to histologic evaluation	In percentage	30 days
Negative Predictive Value of 99mTc-PSMA RGS for salvage surgery for recurrent PC compared to histologic evaluation	In percentage	30 days

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2023
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: September 15, 2022
• First Submitted That Met QC Criteria: September 22, 2022
• First Posted (Actual): September 26, 2022

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: recurrent prostate cancer; ADT; PSMA-radioguided surgery
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: N21TRA

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