Dosimetry, Safety and Potential Benefit of 177Lu-PSMA-617 Prior to Prostatectomy (LuTectomy)

Study of the Dosimetry, Safety and Potential Benefit of 177Lu-PSMA-617 Radionuclide Therapy Prior to Radical Prostatectomy in Men With High-risk Localised Prostate Cancer

This clinical trial will evaluate the dosimetry, efficacy and toxicity of Lu-PSMA in men with high PSMA-expressing high-risk localized or locoregional advanced prostate cancer (HRCaP) undergoing radical prostatectomy (RP) and pelvic lymph node dissection (PLND)

Study Overview

• Status: Active, not recruiting
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Drug: 177Lu-PSMA-617

Detailed Description

This open label, phase I/II non-randomised clinical trial will evaluate the dosimetry, efficacy and toxicity of Lu-PSMA in men with high PSMA-expressing high-risk localized or locoregional advanced prostate cancer (HRCaP) undergoing radical prostatectomy (RP) and pelvic lymph node dissection (PLND). Patients will receive one or two cycles of 177Lu-PSMA followed by surgery. The primary objective is to determine the radiation absorbed dose in the prostate and involved lymph nodes. Secondary objectives include evaluating imaging response to therapy using PSMA-PET, biochemical response, pathological response, adverse effects of Lu-PSMA and surgical safety, and health-related Quality of Life (QoL).

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

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient has provided written informed consent.
• Male patient aged 18 or over at the time of screening
• Histologically confirmed adenocarcinoma of the prostate, in a patient scheduled for RP and PLND with curative intent

• High or high-intermediate risk localised or locoregional prostate cancer (HRCaP) by European Association of Urology (EAU) criteria, including any of the following:

  • PSA > 20 ng/mL
  • ISUP grade group 3-5
  • Clinical T-stage by digital rectal examination (DRE) of T2c or higher
  • N1 disease (involvement of lymph nodes at or below the bifurcation of the common iliac arteries)
  • defined radiologically (CT/ MRI, or PSMA PET).
• High PSMA avidity on 68Ga-PSMA PET/CT, defined as an SUVmax of ≥ 20
• Normal baseline haematological function; haemoglobin 13.5-17.5g/dl), total white blood cell count (4-11 x 109/l), platelets (150-400 x 109/l), neutrophils (2-7.5 x 109/l) and lymphocytes (1-4 x 109/l)
• Normal baseline serum biochemistry; sodium 135-145 nmol/l, potassium 3.5-5 nmol/l, chloride 98-108 nmol/l, urea 3-9.2 nmol/l, creatinine 60-120μmol/l
• Willing and able to comply with all study requirements including all treatments and required assessments including follow up

Exclusion Criteria:

• Prostate cancer with significant neuroendocrine or other rare variant pathology
• Prior treatment for prostate cancer including radiotherapy and/or androgen deprivation therapy.
• Evidence of metastatic disease involving bone, viscera, or lymph nodes superior to the common iliac bifurcation based on CT, MRI, WBBS or PSMA PET/CT.
• Renal impairment [GFR < 60mL/min].
• Sjogren's syndrome.
• A history of or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.

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: 177Lu-PSMA-617 followed by prostatectomy	Drug: 177Lu-PSMA-617; Patients 1-10 will be given 5GBq of 177Lu-PSMA. Patients 11-20 will be given 2 cycles of 5GBq of 177Lu-PSMA, separated by 6 weeks.; Other Names: 177Lu-PSMA; [177Lu]Lu-PSMA-617; Lu-PSMA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the radiation absorbed dose in the prostate and involved lymph nodes following one or two administrations of Lu-PSMA in men with HRCaP prior to radical prostatectomy	Establishing the absorbed radiation dose in the prostate and involved lymph nodes (Gy)	Determined using imaging at 4, 24 and 96 hrs after administration of Lu-PSMA

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the imaging response to therapy using PSMA-PET	PSMA PET response to therapy (complete metabolic response, partial metabolic response, stable metabolic disease, progressive metabolic disease)	6 weeks following final administration of Lu-PSMA
To evaluate the biochemical response to therapy	PSA response	6 weeks following final administration of Lu-PSMA
To evaluate pathologic response in the prostate following prostatectomy	Pathological response (complete response, minimal residual disease)	After prostatectomy, approximately 6 weeks from final Lu-PSMA administration
To evaluate toxicity of Lu-PSMA	Assessment of toxicity of Lu-PSMA using Common Terminology Criteria for Adverse Events (CTCAE) v5	Until 8 weeks after prostatectomy
To evaluate the surgical safety of prostatectomy following Lu-PSMA	Surgical safety will be assessed using using the Clavien-Dindo classification of surgical complications	Until 8 weeks after prostatectomy
To evaluate overall health-related Quality of Life (QoL)	QoL indices will be scored using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire	baseline, immediately before 2nd cycle Lu-PSMA, immediately before surgery, 8 weeks post surgery, annually up to 3 years
To evaluate prostate cancer health-related Quality of Life (QoL)	QoL indices will be scored using European Organisation for Research and Treatment of Cancer (EORTC) QLQ-PR25 questionnaire	baseline, immediately before 2nd cycle Lu-PSMA, immediately before surgery, 8 weeks post surgery, annually up to 3 years
To evaluate patient function and bother after prostatectomy	Indices will be scored using the Expanded Prostate Cancer Index Composite (EPIC)-26 questionnaire	baseline, immediately before 2nd cycle Lu-PSMA, immediately before surgery, 8 weeks post surgery, annually up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the time to biochemical recurrence (BCR) [PSA>0.2 ng/mL post-RP]	Biochemical recurrence (BCR) will be measured from the time of surgery to the first rise of the PSA to ≥0.2 ng/mL	To be determined as it is an exploratory endpoint up to 3 years
To determine the relationship between PSMA PET imaging parameters and absorbed dose	Determination of the relationship between screening PSMA PET imaging parameters including molecular tumour volume parameters and absorbed dose in the prostate and involved lymph nodes	baseline PSMA PET within 45 days of Lu-PSMA administration
To identify tissue and blood and serum biomarkers associated with clinical outcomes	Determination of relevant predictive biomarkers associated with treatment outcomes and response	To be determined as it is an exploratory endpoint up to 3 years

Collaborators and Investigators

• Sponsor: Peter MacCallum Cancer Centre, Australia
• Collaborators: Endocyte; Movember Foundation; Medical Research Future Fund; E.J. Whitten Foundation Prostate Cancer Research Centre
• Investigators: Principal Investigator: Declan Murphy, Peter MacCallum Cancer Centre, Australia; Principal Investigator: Michael S Hofman, Peter MacCallum Cancer Centre, Australia; Principal Investigator: John Violet, Peter MacCallum Cancer Centre, Australia

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2020
• Primary Completion (Actual): December 22, 2022
• Study Completion (Estimated): December 30, 2023

Study Registration Dates

• First Submitted: May 21, 2020
• First Submitted That Met QC Criteria: June 10, 2020
• First Posted (Actual): June 12, 2020

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 17, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Prostate Cancer; prostate specific membrane antigen; 177Lu-PSMA; Radionuclide Therapy; Theranostics
• 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; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; 177Lu-PSMA-617
• Other Study ID Numbers: 19_245

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