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

NCT ID: NCT04343885

Last Updated: 2025-07-11

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-21
• Study Completion Date: 2026-03-31

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).

Detailed Description

This is an open label, randomised, stratified, 2-Arm, multi-centre, phase 2 clinical trial recruiting 140 newly-diagnosed high-volume mHNPC patients at 11 Australian centres over a period of 18 months. Patients will be randomised to the experimental Arm (177Lu-PSMA followed by docetaxel) or standard-of-care Arm (docetaxel) in a 1:1 ratio. All patients will receive ADT continuously throughout the trial. Patients will be stratified according to disease volume by conventional imaging (low-volume vs. high-volume) and duration of ADT at time of registration (≤ 28 days vs. > 28 days).

Conditions

Metastatic Hormone Naive Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

177Lu-PSMA+ Docetaxel

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

Group Type: EXPERIMENTAL

177Lu-PSMA-617

Intervention Type: DRUG

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

Docetaxel

Intervention Type: DRUG

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

Docetaxel (Control)

Docetaxel 75 mg/m2 every 3 weeks x 6 cycles

Group Type: OTHER

Docetaxel

Intervention Type: DRUG

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

Interventions

177Lu-PSMA-617

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

Intervention Type: DRUG

Docetaxel

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

Intervention Type: DRUG

Other Intervention Names

177Lu-PSMA-617 also referred to as 177Lu-PSMA; Taxotere (trade name)

Eligibility Criteria

Inclusion Criteria

1. Patient has provided written informed consent

2. Male aged 18 years or older at screening

3. Prostate cancer diagnosed within 12 weeks of commencement of screening

4. 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

5. Evidence of metastatic disease on CT and/or bone scan

6. PSA > 10ng/ml prior to commencement of medical ADT or surgical orchidectomy

7. 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)

8. Have a performance status of 0-2 on the ECOG Performance Scale (see Appendix 1)

9. Life expectancy greater than 6 months with treatment

10. Assessed by a medical oncologist as suitable for treatment with docetaxel

11. Patients must agree to use an adequate method of contraception

12. Willing and able to comply with all study requirements, including all treatments and required assessments including follow-up

1. Significant PSMA avidity on 68Ga-PSMA PET/CT, defined after central review as a minimum uptake of SUVmax 15 at a site of disease

2. 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)

Exclusion Criteria

1. 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

2. Symptomatic cord compression, or clinical or imaging findings concerning for impending cord compression

3. Central nervous system metastases

4. Patients with Sjogren's syndrome

5. 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

6. 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)

1. 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Movember Foundation

OTHER

Sponsor Role: collaborator

Prostate Cancer Research Alliance

UNKNOWN

Sponsor Role: collaborator

United States Department of Defense

FED

Sponsor Role: collaborator

Advanced Accelerator Applications

INDUSTRY

Sponsor Role: collaborator

Australia's Nuclear Science and Technology Organisation (ANSTO)

UNKNOWN

Sponsor Role: collaborator

Australian and New Zealand Urogenital and Prostate Cancer Trials Group

OTHER

Sponsor Role: collaborator

Australasian Radiopharmaceutical Trials network (ARTnet)

UNKNOWN

Sponsor Role: collaborator

Centre for Biostatistics and Clinical Trials (BaCT)

UNKNOWN

Sponsor Role: collaborator

Peter MacCallum Cancer Centre, Australia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arun Azad, MBBS PhD FRACP

Role: PRINCIPAL_INVESTIGATOR

Peter MacCallum Cancer Centre, Australia

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

Role: PRINCIPAL_INVESTIGATOR

Peter MacCallum Cancer Centre, Australia

Locations

Liverpool Hospital

Liverpool, New South Wales, Australia

Royal North Shore

St Leonards, New South Wales, Australia

St Vincent's Hospital Sydney

Sydney, New South Wales, Australia

Chris O'Brien Lifehouse

Sydney, New South Wales, Australia

Royal Brisbane and Women's Hospital

Brisbane, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Cabrini Hospital

Malvern, Victoria, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Austin Health

Melbourne, Victoria, Australia

Alfred Hospital

Prahran, Victoria, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Countries

Australia

References

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.

Reference Type: DERIVED

PMID: 39293461 (View on PubMed)

Other Identifiers

19/195

Identifier Type: -

Identifier Source: org_study_id