Lu-PSMA for Oligometastatic Prostate Cancer Treated With STereotactic Ablative Radiotherapy

NCT ID: NCT05560659

Last Updated: 2025-07-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-14
• Study Completion Date: 2027-05-31

Brief Summary

The aim of this study is to assess the progression free survival (PFS) of SABR alone and SABR + 177Lu-prostate-specific membrane antigen (PSMA) in patients with oligometastatic prostate cancer undergoing PSMA positron emission tomography (PET) staging.

Detailed Description

Metastatic disease in patients involves treatment including systemic chemotherapy, hormonal therapy and androgen deprivation therapy. "Oligometastases" was termed to describe a state of metastatic transition wherein the cancer cells travel from the original site of tumour to other parts of the body and form fewer number of tumours. Sustained systemic therapies such as chemotherapy have been used as the Standard of care (SOC) in most cases. Novel radiotherapy like Lutetium-177 PSMA radionuclide therapy have been explored in earlier disease settings to further improve outcomes. Based on evidence from few previous trials and emerging safety data from ongoing trials, it is an effective addition to SOC to further improve patient outcomes.

The detection of prostate cancer can be done by a highly sensitive and specific test using the PSMA-PET small molecules. The evidence of high uptake of these PSMA-PET small molecules assists in selection of patients potentially suitable for novel PSMA targeted radionuclide therapy. Previous studies have demonstrated novel molecular imaging techniques, particularly PSMA PET/CT in the biochemical recurrence setting is leading to an increasing number of patients being diagnosed with oligometastatic disease which would not have been detected using conventional imaging techniques.

The Stereotactic ablative body radiotherapy (SABR) is also an emerging localised treatment option for oligometastatic prostate cancer. It delivers a highly focused beam of external radiation concentrated over a tumour and has been used to treat low volume metastatic disease to delay the use of systemic therapies. Results from previous studies show that it a safe, well-tolerated and progressively used in real-world clinical practice to treat patients with low volume of metastatic cancer. Based on the results of a previous trial done by this team, patients with one to three sites of disease treated with a single session of SABR showed promising outcomes.

The aim of this trial is to evaluate the progression free survival of SABR alone and SABR + 177Lu-prostate-specific membrane antigen (PSMA) in patients with oligometastatic prostate cancer undergoing PSMA positron emission tomography (PET) staging.

92 men with oligometastatic prostate cancer will be enrolled in this trial and split into 1:1 ratio to either stereotactic ablative body radiotherapy (SABR) alone or SABR plus 2 cycles of 177Lu-PSMA over a period of 24 months.

Conditions

Oligometastatic Prostate Cancer

Study Design

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

Study Groups

Stereotactic ablative body radiotherapy (SABR) alone

1-3 fractions of SABR to all sites of disease

Group Type: NO_INTERVENTION

No interventions assigned to this group

SABR plus 2 cycles of 177Lu-PSMA

cycles of 177Lu-PSMA with 1-3 fractions of SABR to all sites of disease between cycle 1 and 2

Group Type: EXPERIMENTAL

177Lu-PSMA

Intervention Type: DRUG

Lutetium-177 (177Lu)-PSMA is a radiopharmaceutical comprised of a small molecule inhibitor of PSMA that binds with high affinity to PSMA, labelled with 177Lu. 177Lu has favourable characteristics for radionuclide therapy emitting both a short-range (1-2mm) cytotoxic beta-particle, minimising irradiation of non-targeted normal tissues, alongside gamma emission that allows imaging. Numerous retrospective series initially demonstrated high clinical activity and limited normal tissue toxicity using PSMA-617 and PSMA-I\&T, which are the most advanced small molecule inhibitors of PSMA, radiolabelled with 177Lu

Interventions

177Lu-PSMA

Lutetium-177 (177Lu)-PSMA is a radiopharmaceutical comprised of a small molecule inhibitor of PSMA that binds with high affinity to PSMA, labelled with 177Lu. 177Lu has favourable characteristics for radionuclide therapy emitting both a short-range (1-2mm) cytotoxic beta-particle, minimising irradiation of non-targeted normal tissues, alongside gamma emission that allows imaging. Numerous retrospective series initially demonstrated high clinical activity and limited normal tissue toxicity using PSMA-617 and PSMA-I\&T, which are the most advanced small molecule inhibitors of PSMA, radiolabelled with 177Lu

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male aged 18 years or older at screening

2. Patient has provided written informed consent

3. Histologically confirmed prostate adenocarcinoma w

4. Prior definitive treatment of the primary with either curative intent radiotherapy and/or surgery

5. Patient has 1-5 sites of nodal or bony metastases on 68Ga-PSMA or 18F-DCFPyL PET/CT

6. Adequate haematological function as defined by:

• Absolute neutrophil count (ANC) ≥1.5 x 109/L
• Platelet count >150x 109/L
• Haemoglobin ≥100 g/L
• Creatinine Clearance ≥ 40mL/min (Cockcroft-Gault formula)

7. Assessed as suitable for SABR by a radiation oncologist

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

9. Have a performance status of 0-1 on the ECOG Performance Scale

Exclusion Criteria

1. Prior systemic therapy for metastatic prostate cancer. Prior ADT is allowed but ADT within 6 months of screening for the study is not allowed. If patients have received prior ADT, serum testosterone levels must be above the lower limit of normal

2. Any visceral (AJCCC M1c) metastases

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

4. 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

5. Has a known additional malignancy that is progressing or required active treatment in the last 2 years Note: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or carcinoma in situ such as breast cancer in situ that has undergone potentially curative therapy are not excluded.

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

Sponsors

Varian Medical Systems

INDUSTRY

Sponsor Role: collaborator

Peter MacCallum Cancer Centre, Australia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

A/Prof. Shankar Siva

Role: PRINCIPAL_INVESTIGATOR

Peter MacCallum Cancer Centre, Australia

Dr Aravind S. Ravi Kumar

Role: PRINCIPAL_INVESTIGATOR

Peter MacCallum Cancer Centre, Australia

Locations

Royal North Shore

St Leonards, New South Wales, Australia

Site Status: RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status: RECRUITING

Sheba Medical Centre

Tel Aviv, , Israel

Site Status: RECRUITING

Countries

Australia; Israel

Central Contacts

Gaurav Sharma

Role: CONTACT

Gaurav.Sharma@petermac.org

+61 3 8559 6830

Annette VanDerHeyden

Role: CONTACT

Annette.VanDerHeyden@petermac.org

+61488048792

Facility Contacts

Thomas Eade

Role: primary

thomas.eade@health.nsw.gov.au

Shankar Siva, MBBS FRANZCR

Role: primary

Michal Safarty

Role: primary

Michal.sarfaty@sheba.health.gov.il

Other Identifiers

20/033

Identifier Type: -

Identifier Source: org_study_id