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

Phase 1
Active, not recruiting
Conditions
Prostatic Neoplasms
Interventions
Registration Number
NCT04430192
Lead Sponsor
Peter MacCallum Cancer Centre, Australia
Brief Summary

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)

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).

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Male
Target Recruitment
20
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

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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
177Lu-PSMA-617 followed by prostatectomy177Lu-PSMA-617177Lu-PSMA-617 followed by prostatectomy
Primary Outcome Measures
NameTimeMethod
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 prostatectomyDetermined using imaging at 4, 24 and 96 hrs after administration of Lu-PSMA

Establishing the absorbed radiation dose in the prostate and involved lymph nodes (Gy)

Secondary Outcome Measures
NameTimeMethod
To evaluate the imaging response to therapy using PSMA-PET6 weeks following final administration of Lu-PSMA

PSMA PET response to therapy (complete metabolic response, partial metabolic response, stable metabolic disease, progressive metabolic disease)

To evaluate the surgical safety of prostatectomy following Lu-PSMAUntil 8 weeks after prostatectomy

Surgical safety will be assessed using using the Clavien-Dindo classification of surgical complications

To evaluate pathologic response in the prostate following prostatectomyAfter prostatectomy, approximately 6 weeks from final Lu-PSMA administration

Pathological response (complete response, minimal residual disease)

To evaluate toxicity of Lu-PSMAUntil 8 weeks after prostatectomy

Assessment of toxicity of Lu-PSMA using Common Terminology Criteria for Adverse Events (CTCAE) v5

To evaluate overall health-related Quality of Life (QoL)baseline, immediately before 2nd cycle Lu-PSMA, immediately before surgery, 8 weeks post surgery, annually up to 3 years

QoL indices will be scored using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire

To evaluate the biochemical response to therapy6 weeks following final administration of Lu-PSMA

PSA response

To evaluate prostate cancer health-related Quality of Life (QoL)baseline, immediately before 2nd cycle Lu-PSMA, immediately before surgery, 8 weeks post surgery, annually up to 3 years

QoL indices will be scored using European Organisation for Research and Treatment of Cancer (EORTC) QLQ-PR25 questionnaire

To evaluate patient function and bother after prostatectomybaseline, immediately before 2nd cycle Lu-PSMA, immediately before surgery, 8 weeks post surgery, annually up to 3 years

Indices will be scored using the Expanded Prostate Cancer Index Composite (EPIC)-26 questionnaire

Trial Locations

Locations (1)

Peter MacCallum Cancer Centre

🇦🇺

Melbourne, Victoria, Australia

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