Clinical trial NCT05560659: Lu-PSMA for Oligometastatic Prostate Cancer Treated With STereotactic Ablative Radiotherapy
Official title: Lu-PSMA for Oligometastatic Prostate Cancer Treated With STereotactic Ablative Radiotherapy, a Randomised Phase II Parallel Cohort Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Oligometastatic Prostate Cancer
Lead sponsor: Peter MacCallum Cancer Centre, Australia
Sponsor class: OTHER
Collaborators: name: Varian Medical Systems
First posted: 2022-09-29
Enrollment: 92
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 with a score of 4 or 5 as defined by the E-PSMA criteria
6. At least one site of disease with SUVmax greater than the SUVmax of liver on PSMA PET (Ga-68 PSMA 11 or F-18 DCFPYL tracers only)
7. 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)
8. Assessed as suitable for SABR by a radiation oncologist
9. Patients must agree to use an adequate method of contraception
10. 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.

Primary outcomes:
measure: Evaluate the (bPFS) of SABR alone and SABR + 177Lu-PSMA
timeFrame: Through study completion, up until 12 months after the last patient commences treatment
Secondary outcomes:
measure: The AEs according to CTCAE v5.0
timeFrame: Through study completion, up until 4 months ± 10 days from the commencement of ADT following progression
measure: The PSA-response rate
timeFrame: Through study completion, up until time of biochemical progression +/- 10 days
measure: The ADT-free survival
timeFrame: Through study completion, up until biochemical progression +/- 10 days
measure: The pattern of recurrence on PSMA PET
timeFrame: Time of biochemical progression +/-10 days
measure: The patient reported quality of life
timeFrame: From the date of randomisation to the date of progression
measure: The MDT PFS
timeFrame: Time point after Cycle 2 (28 days follow up post Cycle 2) until biochemical progression
measure: The overall survival
timeFrame: Time point post randomisation to the date of death from any cause
measure: Healthcare costs associated with delivering the intervention and management of AEs
timeFrame: Through study completion, an average of 3 years
measure: The PET-PFS
timeFrame: Through study completion, from the date of randomisation to the date of radiological progression or death from any cause, whichever comes first.
Other outcomes:
Locations:
city: St Leonards
country: Australia
facility: Royal North Shore
state: New South Wales
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Tel Aviv
country: Israel
facility: Sheba Medical Centre
Study officials:
affiliation: Peter MacCallum Cancer Centre, Australia
name: A/Prof. Shankar Siva
role: PRINCIPAL_INVESTIGATOR
affiliation: Peter MacCallum Cancer Centre, Australia
name: Dr Aravind S. Ravi Kumar
role: PRINCIPAL_INVESTIGATOR
References: