External Beam Therapy With Theranostic Radioligand Therapy for Oligometastatic Prostate Cancer (ProstACT TARGET)

A Single Arm, Phase 2 Trial of External Beam Radiation Therapy (EBRT) in Combination With 177Lu-DOTA-TLX591-CHO in Patients With Biochemically Recurrent Oligometastatic, Prostate Specific Membrane Antigen-Expressing Prostate Cancer

This is a phase II trial to evaluate the therapeutic efficacy of a radiolabelled PSMA-targeting antibody, 177Lu-TLX591, given in combination with external beam radiation therapy (EBRT) in patients with biochemically recurrent, oligometastatic, PSMA-expressing prostate cancer. TLX591 is being developed as a PSMA-targeting antibody to be radiolabelled with a therapeutic radiosotope for the treatment of PSMA-expressing tumours.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Biological: 177Lu-DOTA-TLX591

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Julie Gisbon; Phone Number: 317-588-9700; Email: julie.gibson@telixpharma.com
• Study Contact Backup: Name: Charlotte Hawkins, PhD; Phone Number: 317-588-9700; Email: charlotte.hawkins@telixpharma.com

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Recruiting
    • GenesisCare St Andrews
  • Tugun, Australia, 4225
    • Recruiting
    • GenesisCare Tugun
    • Contact: David Christie, MD
  • New South Wales
    • St Leonards, New South Wales, Australia
      • Recruiting
      • Genesiscare North Shore
      • Contact: Laurence Krieger; Email: laurence_krieger@hotmail.com
  • Western Australia
    • Perth, Western Australia, Australia, 6150
      • Recruiting
      • GenesisCare Murdoch
      • Contact: Nat Lenzo, MD; Phone Number: +61 02 8236 3300; Email: Nat.Lenzo@genesiscare.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Signed Informed Consent Form
• Male, aged ≥ 18 years
• Estimated life expectancy of at least 6 months
• Eastern Cooperative Oncology Group (ECOG) score 0 - 2
• Biopsy proven prostate adenocarcinoma with Gleason Score 7 or more at primary presentation
• Previous Radical Prostatectomy (RP) with curative intent (+/- post-operative radiotherapy to prostate bed)
• Biochemical relapse, as defined by EAU-ESTRO-SIOG Guidelines (serum PSA > 0.2 ng/mL, confirmed by repeat measurements)
• PSMA-ligand avid pelvic nodal disease on PSMA-ligand PET/CT, with visualised disease confined to the pelvis with or without evidence of PSMA-avid disease in the prostate bed
• At least one pelvic nodal lesion ≥ 5 mm in the greatest dimension. SUVmax > 9 in enlarged nodes; SUVmax > 3 in nodes 5 mm or less
• Oligometastatic disease as defined by ≤ 5 metastatic lymph nodes
• Metastatic lymph nodes not beyond the aortic bifurcation
• Non-castrate levels of testosterone (> 20 ng/dL)
• Chemotherapy naïve
• Adequate renal function: Cr Cl ≥ 40 mL/min (determined by Cockcroft-Gault formula)
• Adequate bone marrow function: Hb > 90 g/L; platelets > 100 x 109/L; neutrophils > 1.5 x 109/L
• Adequate liver function: bilirubin < 1.5 x upper limit of normal (ULN); AST, ALT, ALP < 2 x ULN; albumin > 30 g/L
• Willing and able to comply with all trial requirements, including all treatments and pre- and post-treatment assessments
• Able to commence treatment within 28 days of enrolment

Exclusion Criteria:

• Previous external beam radiotherapy to pelvis for other malignancies or medical conditions (except for post-operative prostate bed radiotherapy for prostate cancer)
• Androgen deprivation therapy within 12 months of trial screening
• Known androgen deficiency
• Bone or visceral metastases
• Lymph node metastases above the aortic bifurcation
• Contraindications to pelvic irradiation as determined by Investigator (e.g., chronic inflammatory bowel disease)
• At increased risk of haemorrhage, or recent history of a thrombotic event (e.g., Deep Vein Thrombosis [DVT]/Pulmonary Embolism [PE]) and/or are using long-term anti-coagulant or anti-platelet agents)
• Known hypersensitivity to any isotope of lutetium (Lu) in any chemical form, or any isotope used in PSMA imaging
• Contraindication to intravenous contrast
• Evidence of urinary tract stricture, or significant urinary/faecal incontinence Presence of active infection at time of screening, or history of serious infection within the previous 4 weeks
• History of any malignancy other than prostate cancer within 5 years of enrolment (excluding localised non-melanoma skin cancers)
• Any uncontrolled significant medical, psychiatric, or surgical condition (e.g., active infection, unstable angina pectoris, cardiac arrhythmia, poorly controlled type 2 diabetes, uncontrolled congestive heart failure, pulmonary disease), or laboratory findings that, in the opinion of the Investigator, may jeopardise the participant's safety or that would limit compliance with the treatment and assessment requirements of the trial
• Any cognitive impairment or other condition that may render the participant unable to adequately understand the requirements, nature, and possible consequences of the trial.
• Intention to father children within a timeframe corresponding with the duration of the allocated treatment regime plus 12 weeks.

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: Single administration of 177Lu-DOTA-TLX591; Two single IV infusions of 76 mCi (2.8 GBq) each (equivalent to a 45 mCi/m2 administered activity in a standard 1.7m2 individual) of 177Lu-DOTA-TLX591, given 14 days apart.	Biological: 177Lu-DOTA-TLX591; TLX591, a monoclonal antibody conjugated with a DOTA chelator and radiolabelled with 177Lu (177Lu-DOTA-TLX591)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine Prostate Specific Antigen Progression Free Survival (PSA PFS)	The time from enrolment to time of PSA increase greater than 25%	Through study completion, up to 2 years

Collaborators and Investigators

• Sponsor: Telix International Pty Ltd

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2022
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): June 30, 2025

Study Registration Dates

• First Submitted: November 25, 2021
• First Submitted That Met QC Criteria: December 5, 2021
• First Posted (Actual): December 7, 2021

Study Record Updates

• Last Update Posted (Estimate): February 27, 2023
• Last Update Submitted That Met QC Criteria: February 24, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: ProstACT TARGET

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