Neoadjuvant PSMA-RLT in Oligometastatic PCa

Neoadjuvant [177Lu]Lu-PSMAI&T Radioligand Therapy (PSMA-RLT) for Patients With Oligometastatic Prostate Cancer Diagnosed Using [68Ga]Ga-PSMA-11 PET Imaging Followed by Radical Prostatectomy: A Prospective Phase II Pilot Study

Prospective single-center phase II study to evaluate the PSA, imaging and pathological response, as well as oncological outcomes of systemic radioligand therapy [177Lu]Lu-PSMAI&T (PSMA-RLT) in patients planned for radical prostatectomy (RP) for oligometastatic prostate cancer (PCa) diagnosed using [68Ga]Ga-PSMA-11 PET examination.

Ten patients with oligometastatic primary PCa diagnosed using [68Ga]Ga-PSMA-11 PET-CT/MRI imaging will be included in this study.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: [177Lu]Lu-PSMA I&T

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sazan Rasul, PhD; Phone Number: 004314040058742; Email: sazan.rasul@meduniwien.ac.at
• Study Contact Backup: Name: Shahrokh F. Shariat, Professor; Phone Number: 004314040026150; Email: shahrokh.shariat@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Contact: Sazan Rasul, PhD; Phone Number: 004314040058742; Email: sazan.rasul@meduniwien.ac.at
    • Contact: Shahrokh F. Shariat, Professor; Phone Number: 004314040026150; Email: shahrokh.shariat@meduniwien.ac.at
    • Principal Investigator: Sazan Rasul, PhD
    • Sub-Investigator: Pawel Rajwa, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Oligometastatic PCa diagnosed using [68Ga]Ga-PSMA-11 imaging defined as M1a and/or M1b positive with ≤5 osseous metastases and/or M1c ≤3 lung metastases
• Eastern Cooperative Oncology Group (ECOG) Performance Status: 0-1
• Patients must have adequate bone marrow reserve: WBC ≥1.5 x 109 /L, Platelets ≥100 x 109 /L and Haemoglobin ≥9 g/dL.
• Patients must have adequate renal function with eGFR ≥ 50mL/min/1.73m2 using the Modification of Diet Renal Disease (MDRD) equation and an Albumin level of ≥2.5 g/dL.
• Patients must be able to sign Informed Consent Form

Exclusion Criteria:

• Concomitant participation in any other interventional trial
• Concurrent severe oncologic and medical conditions that result in patients not having a life expectancy of longer than the duration of the trial.
• Nonmetastatic PCa on [68Ga]Ga-PSMA-11 imaging
• >5 osseous metastases on [68Ga]Ga-PSMA-11 imaging
• Visceral metastases, apart from lungs
• Age > 75 years.
• Ongoing or previous androgen deprivation therapy with agonist or antagonist therapies.
• Presence of clinically relevant somatic or psychiatric diseases that might interfere with the objectives and assessments of the study.
• Complete urinary out-flow obstruction or severe unmanageable urinary incontinence

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Oligometastatic prostate cancer diagnosed using [68Ga]Ga-PSMA-11 PET imaging; Patients with oligometastatic PCa diagnosed using [68Ga]Ga-PSMA-11 imaging defined as M1a and/or M1b positive with ≤5 osseous metastases and/or M1c ≤3 lung metastases will receive 2 cycles of 5 GBq [177Lu]Lu-PSMA I&T at 6-week intervals prior radical prostatectomy.	Drug: [177Lu]Lu-PSMA I&T; 2 cycles of 5 GBq [177Lu]Lu-PSMA I&T at 6-week intervals prior radical prostatectomy for patients with oligometastatic prostate cancer; Other Names: PSMA-RLT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events [Safety and Tolerability] of neoadjuvant PSMA-RLT and radical prostatectomy	Using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Furthermore, regular estimation of patient's ability to perform their usual everyday activities using Karnofsky performance status scale that ranges between a maximum of 100 percent (no restrictions) and 0 percent (death) and Eastern Cooperative Oncology Group Status scale that ranges from 0 (complete health) to 5 (death).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSA response to neoadjuvant PSMA-RLT and radical prostatectomy	in term of PSA decline of ≥ 50% from baseline value	24 months
Imaging response and stability to neoadjuvant PSMA-RLT and radical prostatectomy	in terms of disappearance of PSMA-avid lesions and/or size regression of the metastatic lymph nodes evaluated based on response evaluation criteria of solid tumor (RECIST) version 1.1.	24 months
Any therapy- and androgen deprivation therapy-free survival after radical prostatectomy,	estimate the time until the start of any therapy- and androgen deprivation therapy	24 months
Estimate time to castration-resistant prostate cancer	estimate the time until no PSA response in terms of PSA decline to androgen deprivation therapy	24 months
Evaluate pathologic response at radical prostatectomy	measured as rates of pathologic complete response, minimal residual disease, pT3 disease, positive surgical margins, and lymph node metastasis.	24 months
Quantification of circulating free tumor DNA (ctDNA)	enumeration of circulating tumor cells (CTCs) during the study period, molecular changes measured in liquid biopsy markers and tissue specimens following PSMA-RLT and radical prostatectomy and during follow-up.	24 months
Assess quality of life under the systemic PSMA-RLT	using the questionnaires: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) and Functional Assessment of Chronic Illness Therapy (FACT-P).	24 months

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: December 25, 2023
• First Submitted That Met QC Criteria: February 6, 2024
• First Posted (Actual): February 14, 2024

Study Record Updates

• Last Update Posted (Actual): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Radical prostatectomy; Oligometastatic prostate cancer; [177Lu]Lu-PSMAI&T; Therapy toxicity
• 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: 1944/2022; 2022-004115-92 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon request, we provide the individual participant data (IPD) available to other researchers.
• IPD Sharing Time Frame: For 2 years after the end of the trail
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No