PSMA-RLT in Biochemically Recurrent PCa

[177Lu]Lu-PSMAI&T Radioligand Therapy (PSMA-RLT) for Patients With Prostate Cancer and Biochemical But Not Radio-morphological Local Recurrence After Primary Therapy With Curative Intent: A Prospective Phase II Pilot Study

Prospective single-center one-arm phase II study in patients with prostate cancer and confirmed biochemical recurrence (BCR) with PSA of ≥ 0.2 ng/ml after radical prostatectomy (RP) or PSA > nadir + 2ng/ml after radiotherapy (RT) but not radio-morphological local recurrence after primary therapy with curative intent receive systemic therapy with only 2 cycles of highly standardized (3 GBq in first cycle and 6 GBq in the second cycle) PSMA-RLT at 6-week intervals.

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 20
• 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: 014040058742; Email: sazan.rasul@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:

• Patients with biochemical recurrence after radical prostatectomy and radiotherapy with a PSA doubling-time (DT) of ≤ 12 months.
• No hormonal therapy within the last 12 months or recovered testosterone levels.
• PSMA PET negative result for local recurrence; presence of distant metastases is allowed: (cN0, cM0/cM1).
• 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 oncological and medical conditions that result in patients not having a life expectancy of longer than one year.
• 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: Biochemical recurrent prostate cancer but not radio-morphological local recurrence; Patients with prostate cancer and confirmed biochemical recurrence with PSA of ≥ 0.2 ng/ml after radical prostatectomy or PSA > nadir + 2ng/ml after radiotherapy but not radio-morphological local recurrence after primary therapy with curative intent will receive systemic therapy with [177Lu]Lu-PSMAI&T radioligand therapy

Drug: [177Lu]Lu-PSMA I&T; 2 cycles (3 GBq in first cycle and 6 GBq in the second cycle) of [177Lu]Lu-PSMAI&T radioligand therapy at 6-week intervals; Other Names: PSMA-RLT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSA response	in term of PSA decline of ≥ 50% from baseline value	12 months
Emergence of therapy toxicity	in terms of pathological (Grade 3) reduction of values of blood count (hemoglobin decreased <8.0 g/dL; <4.9 mmol/L; <80 g/L; platelet count decreased <50,000 - 25,000/mm3; <50.0 - 25.0 x 10e9 /L and white blood cell decreased <2000 - 1000/mm3; <2.0 - 1.0 x 10e9 /L. ), kidney (creatinine increased > 3.0 x baseline or >3.0 - 6.0 x upper limit of normal (UNL)) and liver functions (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and GGT increased >5.0 - 20.0 x ULN if baseline was normal or >5.0 - 20.0 x baseline if baseline was abnormal; albumin <2 g/dL or <20 g/L; bilirubin increased >3.0 - 10.0 x ULN if baseline was normal or >3.0 - 10.0 x baseline if baseline was abnormal and lactate dehydrogenase increased > ULN.), assessed by Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to PSA value progression	to evaluate progression free survival	18 months
androgen deprivation therapy- and other treatment-free survival	analyze the time until the start of androgen deprivation therapy	18 months
Evaluation of life quality of the treated patients	Using the questionnaires: FACT-P, EORTC QLQ	18 months
Assess time to imaging progression	In terms of appearance of new PSMA-avid lesions and/or size progression of the metastatic lymph nodes evaluated based on response evaluation criteria of solid tumor (RECIST) version 1.1.	18 months
Quantification of circulating free tumor DNA	Quantification of circulating free tumor DNA (ctDNA), enumeration of circulating tumor cells (CTCs) before and following [177Lu]Lu-PSMAI&T-RLT and analyse molecular changes in liquid biopsy markers following [177Lu]Lu-PSMAI&T-RLT.	18 months

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: December 25, 2023
• First Submitted That Met QC Criteria: January 21, 2024
• First Posted (Actual): January 23, 2024

Study Record Updates

• Last Update Posted (Actual): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 10, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Prostate cancer; Biochemical recurrence; [177Lu]Lu-PSMA I&T; PSMA-radioligand therapy; PSA value
• 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: 1938/2022; 2022-003713-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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