Clinical trial NCT04430192: Dosimetry, Safety and Potential Benefit of 177Lu-PSMA-617 Prior to Prostatectomy
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Prostatic Neoplasms
Keywords: 177Lu-PSMA
Prostate Cancer
Radionuclide Therapy
Theranostics
prostate specific membrane antigen
Lead sponsor: Peter MacCallum Cancer Centre, Australia
Sponsor class: OTHER
Collaborators: name: Movember Foundation
name: Medical Research Future Fund
name: Endocyte
name: E.J. Whitten Foundation Prostate Cancer Research Centre
First posted: 2020-06-12
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Determined using imaging at 4, 24 and 96 hrs after administration of Lu-PSMA
Secondary outcomes:
measure: To evaluate the imaging response to therapy using PSMA-PET
timeFrame: 6 weeks following final administration of Lu-PSMA
measure: To evaluate the biochemical response to therapy
timeFrame: 6 weeks following final administration of Lu-PSMA
measure: To evaluate pathologic response in the prostate following prostatectomy
timeFrame: After prostatectomy, approximately 6 weeks from final Lu-PSMA administration
measure: To evaluate toxicity of Lu-PSMA
timeFrame: Until 8 weeks after prostatectomy
measure: To evaluate the surgical safety of prostatectomy following Lu-PSMA
timeFrame: Until 8 weeks after prostatectomy
measure: To evaluate overall health-related Quality of Life (QoL)
timeFrame: baseline, immediately before 2nd cycle Lu-PSMA, immediately before surgery, 8 weeks post surgery, annually up to 3 years
measure: To evaluate prostate cancer health-related Quality of Life (QoL)
timeFrame: baseline, immediately before 2nd cycle Lu-PSMA, immediately before surgery, 8 weeks post surgery, annually up to 3 years
measure: To evaluate patient function and bother after prostatectomy
timeFrame: baseline, immediately before 2nd cycle Lu-PSMA, immediately before surgery, 8 weeks post surgery, annually up to 3 years
Other outcomes:
measure: To determine the time to biochemical recurrence (BCR) [PSA>0.2 ng/mL post-RP]
timeFrame: To be determined as it is an exploratory endpoint up to 3 years
measure: To determine the relationship between PSMA PET imaging parameters and absorbed dose
timeFrame: baseline PSMA PET within 45 days of Lu-PSMA administration
measure: To identify tissue and blood and serum biomarkers associated with clinical outcomes
timeFrame: To be determined as it is an exploratory endpoint up to 3 years
Locations:
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
Study officials:
affiliation: Peter MacCallum Cancer Centre, Australia
name: Declan Murphy
role: PRINCIPAL_INVESTIGATOR
affiliation: Peter MacCallum Cancer Centre, Australia
name: Michael S Hofman
role: PRINCIPAL_INVESTIGATOR
affiliation: Peter MacCallum Cancer Centre, Australia
name: John Violet
role: PRINCIPAL_INVESTIGATOR
References: