Prostatic Neoplasms
Conditions
Keywords
177Lu-PSMA, Prostate Cancer, Radionuclide Therapy, Theranostics, prostate specific membrane antigen
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).
Interventions
DRUG177Lu-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.
Sponsors
Movember Foundation
Medical Research Future Fund
Endocyte
E.J. Whitten Foundation Prostate Cancer Research Centre
Peter MacCallum Cancer Centre, Australia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Determined 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
| Measure | Time frame | Description |
|---|---|---|
| To evaluate toxicity of Lu-PSMA | Until 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 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 prostatectomy | baseline, 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 |
| To evaluate the imaging response to therapy using PSMA-PET | 6 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 biochemical response to therapy | 6 weeks following final administration of Lu-PSMA | PSA response |
| To evaluate pathologic response in the prostate following prostatectomy | After prostatectomy, approximately 6 weeks from final Lu-PSMA administration | Pathological response (complete response, minimal residual disease) |
| To evaluate the surgical safety of prostatectomy following Lu-PSMA | Until 8 weeks after prostatectomy | Surgical safety will be assessed using using the Clavien-Dindo classification of surgical complications |
Other
| Measure | Time frame | Description |
|---|---|---|
| To identify tissue and blood and serum biomarkers associated with clinical outcomes | To be determined as it is an exploratory endpoint up to 3 years | Determination of relevant predictive biomarkers associated with treatment outcomes and response |
| To determine the relationship between PSMA PET imaging parameters and absorbed dose | baseline PSMA PET within 45 days of Lu-PSMA administration | 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 |
| To determine the time to biochemical recurrence (BCR) [PSA>0.2 ng/mL post-RP] | To be determined as it is an exploratory endpoint up to 3 years | Biochemical recurrence (BCR) will be measured from the time of surgery to the first rise of the PSA to ≥0.2 ng/mL |
Countries
Australia
Outcome results
None listed