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Lu-PSMA for Oligometastatic Prostate Cancer Treated With STereotactic Ablative Radiotherapy (POPSTAR II)

Primary Purpose

Oligometastatic Prostate Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
177Lu-PSMA
Sponsored by
Peter MacCallum Cancer Centre, Australia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oligometastatic Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male aged 18 years or older at screening
  2. Patient has provided written informed consent
  3. Histologically confirmed prostate adenocarcinoma with prior definitive surgical or radiotherapy treatment
  4. Prior definitive treatment of the primary with either curative intent radiotherapy or surgery, with no evidence of PSMA avid disease in the prostate/prostate bed
  5. Assessed as suitable for SABR with 1-5 sites of nodal or bony metastases on PSMA PET/computed tomography (CT). If nodal disease only, then at least one site of extra-pelvic nodal disease, defined as located above the bifurcation of the common iliac arteries
  6. At least one site of disease with SUVmax twice 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. Have a performance status of 0-1 on the Eastern Co-operative Oncology Group (ECOG) Performance Scale (see Appendix 1)
  9. Patients must agree to use an adequate method of contraception
  10. Patients must be willing and able to comply with all study requirements, including all treatments and required scheduled assessments

Exclusion Criteria:

  1. Small cell or neuroendocrine differentiation of prostate cancer
  2. Prior systemic therapy, radiation therapy, or surgery for metastatic prostate cancer. Prior ADT is allowed but ADT within six 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
  3. No sites of PSMA negative metastatic disease evident on CT/bone scan
  4. Any visceral (AJCCC M1c) metastases
  5. Symptomatic cord compression, or clinical or imaging findings concerning for impending cord compression
  6. 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
  7. Prior diagnosis of another cancer within 3 years of current diagnosis with the exception of successfully treated basal cell or squamous cell skin carcinoma, adequately treated papillary thyroid carcinoma or adequately treated non-muscle invasive bladder cancer (Tis, Ta and low grade T1 tumours)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    No Intervention

    Experimental

    Arm Label

    Stereotactic ablative body radiotherapy (SABR) alone

    SABR plus 2 cycles of 177Lu-PSMA

    Arm Description

    1-3 fractions of SABR to all sites of disease

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

    Outcomes

    Primary Outcome Measures

    Evaluate the (bPFS) of SABR alone and SABR + 177Lu-PSMA
    The biochemical progression free survival (bPFS) of SABR alone and SABR + 177Lu-prostate-specific membrane antigen (PSMA) in patients with oligometastatic prostate cancer undergoing PSMA positron emission tomography (PET) staging.

    Secondary Outcome Measures

    The AEs according to CTCAE v5.0
    The type, grade and relationship to treatment of AEs will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0
    The PSA-response rate
    PSA response will be defined as a 50% or greater decrease in PSA from baseline to the lowest post-baseline PSA result
    The ADT-free survival
    ADT-FS is defined as the time from randomisation to the date of initiation of androgen deprivation therapy or date of death due to any cause
    The pattern of recurrence on PSMA PET
    Pattern of relapse will be evaluated on the PSMA PET at progression in relation to baseline PSMA PET, including: a) number of new sites of disease; b) location of new disease of disease (pelvic nodes, extra-pelvic nodes, bone, viscera); c) progression at prior sites (yes or no)
    The patient reported quality of life
    QoL will be assessed using the EORTC QLQC-30 and EQ-5D-5L questionnaires
    The MDT PFS
    MDT PFS is defined as the time from first MDT after initial treatment to first documented subsequent disease progression (biochemical, or clinical using the same definition as the primary endpoint) or date of death, whichever comes first. Only patients who received MDT as the only treatment modality after initial treatment will be included.
    The overall survival
    OS is defined as the time from randomisation to the date of death from any cause
    Healthcare costs associated with delivering the intervention and management of AEs
    Health economic analysis is planned to assess the real-world cost-effectiveness and broader economic impact of using 177Lu-PSMA + SABR compared to SABR alone (if an effect is observed). Costs included in the analysis will focus on those relevant to the intervention (177Lu-PSMA) including treatment-related hospitalisations, clinic visits, PSMA PET scans, and associated medical service utilisation. Additionally, healthcare resource used and their associated costs including those associated with the complications arising from each study arm will be extracted from hospital administrative records and data collected during the trial (e.g., CTCAE v 5.0 Toxicity Record) and compared to provide an understanding of overall costs.
    The PET-PFS
    PET-PFS is defined as the time from randomisation to the date of radiological progression on PSMA PET/CT scan or death due to any cause, whichever comes first. Patients alive without a rise in PSA will be censored at last PSA assessment

    Full Information

    First Posted
    February 17, 2022
    Last Updated
    July 27, 2023
    Sponsor
    Peter MacCallum Cancer Centre, Australia
    Collaborators
    Varian Medical Systems
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05560659
    Brief Title
    Lu-PSMA for Oligometastatic Prostate Cancer Treated With STereotactic Ablative Radiotherapy
    Acronym
    POPSTAR II
    Official Title
    Lu-PSMA for Oligometastatic Prostate Cancer Treated With STereotactic Ablative Radiotherapy, a Randomised Phase II Parallel Cohort Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 2023 (Anticipated)
    Primary Completion Date
    May 2025 (Anticipated)
    Study Completion Date
    May 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Peter MacCallum Cancer Centre, Australia
    Collaborators
    Varian Medical Systems

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Oligometastatic Prostate Cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    92 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Stereotactic ablative body radiotherapy (SABR) alone
    Arm Type
    No Intervention
    Arm Description
    1-3 fractions of SABR to all sites of disease
    Arm Title
    SABR plus 2 cycles of 177Lu-PSMA
    Arm Type
    Experimental
    Arm Description
    cycles of 177Lu-PSMA with 1-3 fractions of SABR to all sites of disease between cycle 1 and 2
    Intervention Type
    Drug
    Intervention Name(s)
    177Lu-PSMA
    Intervention Description
    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
    Primary Outcome Measure Information:
    Title
    Evaluate the (bPFS) of SABR alone and SABR + 177Lu-PSMA
    Description
    The biochemical progression free survival (bPFS) of SABR alone and SABR + 177Lu-prostate-specific membrane antigen (PSMA) in patients with oligometastatic prostate cancer undergoing PSMA positron emission tomography (PET) staging.
    Time Frame
    Through study completion, up until 12 months after the last patient commences treatment
    Secondary Outcome Measure Information:
    Title
    The AEs according to CTCAE v5.0
    Description
    The type, grade and relationship to treatment of AEs will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0
    Time Frame
    Through study completion, up until 4 months ± 10 days from the commencement of ADT following progression
    Title
    The PSA-response rate
    Description
    PSA response will be defined as a 50% or greater decrease in PSA from baseline to the lowest post-baseline PSA result
    Time Frame
    Through study completion, up until time of biochemical progression +/- 10 days
    Title
    The ADT-free survival
    Description
    ADT-FS is defined as the time from randomisation to the date of initiation of androgen deprivation therapy or date of death due to any cause
    Time Frame
    Through study completion, up until biochemical progression +/- 10 days
    Title
    The pattern of recurrence on PSMA PET
    Description
    Pattern of relapse will be evaluated on the PSMA PET at progression in relation to baseline PSMA PET, including: a) number of new sites of disease; b) location of new disease of disease (pelvic nodes, extra-pelvic nodes, bone, viscera); c) progression at prior sites (yes or no)
    Time Frame
    Time of biochemical progression +/-10 days
    Title
    The patient reported quality of life
    Description
    QoL will be assessed using the EORTC QLQC-30 and EQ-5D-5L questionnaires
    Time Frame
    From the date of randomisation to the date of progression
    Title
    The MDT PFS
    Description
    MDT PFS is defined as the time from first MDT after initial treatment to first documented subsequent disease progression (biochemical, or clinical using the same definition as the primary endpoint) or date of death, whichever comes first. Only patients who received MDT as the only treatment modality after initial treatment will be included.
    Time Frame
    Time point after Cycle 2 (28 days follow up post Cycle 2) until biochemical progression
    Title
    The overall survival
    Description
    OS is defined as the time from randomisation to the date of death from any cause
    Time Frame
    Time point post randomisation to the date of death from any cause
    Title
    Healthcare costs associated with delivering the intervention and management of AEs
    Description
    Health economic analysis is planned to assess the real-world cost-effectiveness and broader economic impact of using 177Lu-PSMA + SABR compared to SABR alone (if an effect is observed). Costs included in the analysis will focus on those relevant to the intervention (177Lu-PSMA) including treatment-related hospitalisations, clinic visits, PSMA PET scans, and associated medical service utilisation. Additionally, healthcare resource used and their associated costs including those associated with the complications arising from each study arm will be extracted from hospital administrative records and data collected during the trial (e.g., CTCAE v 5.0 Toxicity Record) and compared to provide an understanding of overall costs.
    Time Frame
    Through study completion, an average of 3 years
    Title
    The PET-PFS
    Description
    PET-PFS is defined as the time from randomisation to the date of radiological progression on PSMA PET/CT scan or death due to any cause, whichever comes first. Patients alive without a rise in PSA will be censored at last PSA assessment
    Time Frame
    Through study completion, from the date of randomisation to the date of radiological progression or death from any cause, whichever comes first.

    10. Eligibility

    Sex
    Male
    Gender Based
    Yes
    Gender Eligibility Description
    Male aged 18 years or older at screening
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Male aged 18 years or older at screening Patient has provided written informed consent Histologically confirmed prostate adenocarcinoma w Prior definitive treatment of the primary with either curative intent radiotherapy and/or surgery 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 At least one site of disease with SUVmax twice the SUVmax of liver on PSMA PET (Ga-68 PSMA 11 or F-18 DCFPYL tracers only) 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) Assessed as suitable for SABR by a radiation oncologist Patients must agree to use an adequate method of contraception Have a performance status of 0-1 on the ECOG Performance Scale Exclusion Criteria: Prior systemic therapy, radiation therapy, or surgery 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 No sites of PSMA negative metastatic disease evident on CT/bone scan Any visceral (AJCCC M1c) metastases Symptomatic cord compression, or clinical or imaging findings concerning for impending cord compression 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 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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Gaurav Sharma
    Phone
    +61 3 8559 6830
    Email
    Gaurav.Sharma@petermac.org
    First Name & Middle Initial & Last Name or Official Title & Degree
    Annette VanDerHeyden
    Phone
    +61488048792
    Email
    Annette.VanDerHeyden@petermac.org
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    A/Prof. Shankar Siva
    Organizational Affiliation
    Peter MacCallum Cancer Centre, Australia
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    Dr Aravind S. Ravi Kumar
    Organizational Affiliation
    Peter MacCallum Cancer Centre, Australia
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    Individual requests for data sharing must be accompanied by ethical approval and will be considered at request

    Learn more about this trial

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

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