In Men With Metastatic Prostate Cancer, What is the Safety and Benefit of Lutetium-177 PSMA Radionuclide Treatment in Addition to Chemotherapy

NCT04343885 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: 19/195
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 12

Brief Summary

This phase 2 randomised clinical trial will compare the effectiveness of Lu-PSMA therapy followed by docetaxel chemotherapy versus docetaxel chemotherapy on its own in patients with newly-diagnosed high-volume metastatic hormone-naive prostate cancer (mHNPC).

Conditions

Metastatic Hormone Naive Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Undetectable prostate specific antigen (PSA) rate at 12 months after commencement of protocol therapy

  Undetectable PSA is defined as PSA ≤ 0.2ng/ml at 12 months after protocol treatment commencement. Patients who experience unequivocal radiographic (by conventional imaging modality) and/or clinical disease progression within 12 months of initiating protocol treatment will be considered as not having undetectable PSA at 12 months.

  Upto 32 months assuming 18 months to complete recruitment, a maximum of 1.6 months from consent to commencement of treatment for last patient and then 12 months from commencement of treatment for last patient.

Secondary Outcomes (8)

• Safety of 177Lu-PSMA followed by docetaxel compared to docetaxel alone

  Through completion of treatment, maximum 26 months.

• Time to development of castration resistance between treatment Arms

  Through study completion, up until 2 years after the last patient commences treatment.

• PSA-progression free survival (PSA-PFS) between treatment Arms

  Through study completion, up until 2 years after the last patient commences treatment.

• Radiographic-PFS (rPFS) between treatment Arms

  Through study completion, up until 2 years after the last patient commences treatment.

• Early PSMA PET response between treatment Arms

  Through completion of 3 months after treatment commencement for last patient, maximum 23 months.

Other Outcomes (2)

• Assess the correlation between PSMA and FDG PET/CT parameters and clinical outcomes

  Through study completion, up until 2 years after the last patient commences treatment.

• Identify biomarkers potentially associated with clinical outcomes

  Through study completion, up until 2 years after the last patient commences treatment.

Study Arms (2)

177Lu-PSMA+ Docetaxel

EXPERIMENTAL

7.5 GBq (± 10%) 177Lu-PSMA every 6 weeks x 2 cycles. Docetaxel 75 mg/m2 commencing 6 weeks later, every 3 weeks x 6 cycles

Drug: 177Lu-PSMA-617; Drug: Docetaxel

Docetaxel (Control)

OTHER

Docetaxel 75 mg/m2 every 3 weeks x 6 cycles

Drug: Docetaxel

Interventions

177Lu-PSMA-617 DRUG

Patients will be given 7.5GBq of 177Lu-PSMA every 6 weeks for 2 cycles.

Also known as: 177Lu-PSMA-617 also referred to as 177Lu-PSMA

177Lu-PSMA+ Docetaxel

Docetaxel DRUG

Docetaxel 75 mg/m2 given every 3 weeks for 6 cycles

Also known as: Taxotere (trade name)

177Lu-PSMA+ Docetaxel; Docetaxel (Control)

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Men with a diagnosis of de novo high-volume mHNPC by PSMA-PET/CT criteria
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has provided written informed consent
• Male aged 18 years or older at screening
• Prostate cancer diagnosed within 12 weeks of commencement of screening
• Histologically or cytologically confirmed adenocarcinoma of the prostate without significant neuroendocrine differentiation or small cell histology OR metastatic disease typical of prostate cancer (i.e. involving bone or pelvic lymph nodes or para-aortic lymph nodes) with a rising serum PSA
• Evidence of metastatic disease on CT and/or bone scan
• PSA \> 10ng/ml prior to commencement of medical ADT or surgical orchidectomy
• Adequate haematological, renal and hepatic functions as defined by:
• Absolute neutrophil count \>1.5 x 109/L
• Platelet count \>100 x 109/L
• Haemoglobin ≥ 90g/L (no red blood cell transfusion in 4 weeks prior to randomisation)
• Creatinine Clearance ≥ 40mL/min (Cockcroft-Gault formula)
• Total bilirubin \< 1.5 x ULN (unless known or suspected Gilbert syndrome)
• Aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 2.0 x ULN (or ≤ 5.0 x ULN in the presence of liver metastases)
• Have a performance status of 0-2 on the ECOG Performance Scale (see Appendix 1)
• Life expectancy greater than 6 months with treatment

You may not qualify if:

• Any prior pharmacotherapy, radiation therapy, or surgery for metastatic prostate cancer. The following exceptions are permitted:
• Up to 4 weeks of ADT with luteinising hormone releasing hormone agonists or antagonists or orchiectomy ± concurrent anti-androgens are permitted prior to commencement of screening. At investigator discretion, patients may start ADT at commencement of protocol therapy
• Up to one course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 14 days prior to registration
• Symptomatic cord compression, or clinical or imaging findings concerning for impending cord compression
• Central nervous system metastases
• Patients with Sjogren's syndrome
• Has a history 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
• Prior diagnosis of another cancer that was:
• More than 3 years prior to current diagnosis with subsequent evidence of disease recurrence or clinical expectation of recurrence greater than 10%
• Within 3 years of current diagnosis with the exception of successfully treated basal cell or squamous cell skin carcinoma or adequately treated non-muscle invasive bladder cancer (Tis, Ta and low grade T1 tumours)
• Significant PSMA avidity on 68Ga-PSMA PET/CT, defined after central review as a minimum uptake of SUVmax 15 at a site of disease
• High-volume metastatic disease on 68Ga-PSMA PET/CT defined as visceral metastases or ≥ 4 bone metastases with ≥ 1 outside the vertebral column and pelvis (extra-axial skeleton)
• Major FDG-PET discordance defined as presence of FDG positive disease with minimal PSMA expression in multiple sites (\>5) or in more than 50% of total disease volume

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead
• Movember Foundation: collaborator
• Prostate Cancer Research Alliance: collaborator
• United States Department of Defense: collaborator
• Advanced Accelerator Applications: collaborator
• Australia's Nuclear Science and Technology Organisation (ANSTO): collaborator
• Australian and New Zealand Urogenital and Prostate Cancer Trials Group: collaborator
• Australasian Radiopharmaceutical Trials network (ARTnet): collaborator
• Centre for Biostatistics and Clinical Trials (BaCT): collaborator

Study Sites (12)

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Royal North Shore

St Leonards, New South Wales, 2065, Australia

Location

St Vincent's Hospital Sydney

Sydney, New South Wales, 2010, Australia

Location

Chris O'Brien Lifehouse

Sydney, New South Wales, 2050, Australia

Location

Royal Brisbane and Women's Hospital

Brisbane, Queensland, 4029, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Cabrini Hospital

Malvern, Victoria, 3144, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Austin Health

Melbourne, Victoria, 3084, Australia

Location

Alfred Hospital

Prahran, Victoria, 3000, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Related Publications (1)

• Azad AA, Bressel M, Tan H, Voskoboynik M, Suder A, Weickhardt AJ, Guminski A, Francis RJ, Saghebi J, Dhiantravan N, Joshua AM, Emmett L, Horvath L, Murphy DG, Hsiao E, Balakrishnar B, Lin P, Redfern A, Macdonald W, Ng S, Lee ST, Pattison DA, Nadebaum D, Kirkwood ID, Hofman MS; UpFrontPSMA Study Team. Sequential [177Lu]Lu-PSMA-617 and docetaxel versus docetaxel in patients with metastatic hormone-sensitive prostate cancer (UpFrontPSMA): a multicentre, open-label, randomised, phase 2 study. Lancet Oncol. 2024 Oct;25(10):1267-1276. doi: 10.1016/S1470-2045(24)00440-6. Epub 2024 Sep 15.

  PMID: 39293461 DERIVED

MeSH Terms

Interventions

Pluvicto; Docetaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Arun Azad, MBBS PhD FRACP

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

• Michael Hofman, MBBS(Hons),FRACP,FAANMS,FICIS

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2020
• First Posted: April 13, 2020
• Study Start: April 21, 2020
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: July 11, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (12)