TheraP: A Randomised Phase 2 Trial of 177Lu-PSMA617 Theranostic Versus Cabazitaxel in Progressive Metastatic Castration Resistant Prostate Cancer (ANZUP Protocol 1603)


Condition: Cancer of the Prostate, Metastatic Cancer

Intervention:

  • Other: 177Lu-PSMA617
  • Drug: Cabazitaxel

Purpose: This open label, randomised, stratified, 2-arm, multicentre, phase 2 trial aims to determine the activity and safety of Lu-PSMA vs cabazitaxel in men with progressive metastatic castration resistant prostate cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03392428

Sponsor: Australian and New Zealand Urogenital and Prostate Cancer Trials Group

Primary Outcome Measures:

  • Measure: Prostate Specific Antigen response rate (PSA RR)
  • Time Frame: Through study completion, on average 4 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Pain Response (PPI and Analgesic Score)
  • Time Frame: Through study completion, on average 4 years
  • Safety Issue:
  • Measure: Objective Tumour Response Rate
  • Time Frame: Through study completion, on average 4 years
  • Safety Issue:
  • Measure: Progression free survival
  • Time Frame: Through study completion, on average 4 years
  • Safety Issue:
  • Measure: PSA progression free survival
  • Time Frame: Through study completion, on average 4 years
  • Safety Issue:
  • Measure: Pain progression free survival
  • Time Frame: Through study completion, on average 4 years
  • Safety Issue:
  • Measure: Radiographic progression free survival
  • Time Frame: Through study completion, on average 4 years
  • Safety Issue:
  • Measure: Health-related quality of life
  • Time Frame: Through study completion, on average 4 years
  • Safety Issue:
  • Measure: Overall survival
  • Time Frame: Through study completion, on average 4 years
  • Safety Issue:
  • Measure: Frequency and severity of adverse events
  • Time Frame: From first study dose to 12 weeks after completing study treatment
  • Safety Issue:

Estimated Enrollment: 200

Study Start Date: January 29, 2018

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • 1. Male aged 18 or older with metastatic adenocarcinoma of the prostate defined by:
  • Documented histopathology of prostate adenocarcinoma OR
  • Metastatic disease typical of prostate cancer (i.e. involving bone or pelvic lymph nodes or para-aortic lymph nodes) 2. Castration-resistant prostate cancer (defined as disease progressing despite castration by orchiectomy or ongoing Luteinizing Hormone-Releasing Hormone (LHRH) analog 3. Progressive disease with rising PSA on 3 consecutive measurements, and PSA ≥ 20 ng/mL 4. Target or non-target lesions according to RECIST 1.1 5. Prior treatment with docetaxel 6. Significant PSMA avidity on 68Ga-PSMA PET/CT, defined as a minimum uptake of SUVmax 20 at a site of disease, and SUVmax > 10 at sites of measurable disease ≥10mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact) 7. ECOG Performance status 0 to 2 8. Assessed by a medical oncologist as suitable for chemotherapy with cabazitaxel 9. Adequate renal function: • Cr Cl ≥ 40mL/min (Cockcroft-Gault formula) 10. Adequate bone marrow function:
  • Platelets ≥ 100 x10 billion /L
  • Hb ≥ 90g/L (no red blood cell transfusion in last 4 weeks)
  • Neutrophils > 1.5 x10 billion/L 11. Adequate liver function:
  • Bilirubin < 1.5 x upper limit of normal (ULN) (or if bilirubin is between 1.5-2x ULN, must have a normal conjugated bilirubin)
  • AST or ALT ≤ 2.0 x ULN (or ≤ 5.0 x ULN in the presence of liver metastases) 12. Estimated life expectancy > 12 weeks 13. Study treatment both planned and able to start within 21 days of randomisation 14. Willing and able to comply with all study requirements, including all treatments (cabazitaxel or Lu-PSMA); and, the timing and nature of all required assessments 15. Signed, written informed consent

Exclusion Criteria:

  1. Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components
  2. Site(s) of disease that are FDG positive with minimal PSMA expression defined as FDG intensity > 68Ga-PSMA activity OR 68Ga-PSMA SUVmax < 10
  3. Sjogren's syndrome
  4. Prior treatment with cabazitaxel or Lu-PSMA
  5. Contraindications to the use of corticosteroid treatment
  6. Active malignancy other than prostate cancer
  7. Concurrent illness, including severe infection that may jeopardise the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety
  8. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse
  9. Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception

Contact:

  • Trial Coordinator
  • 61295625363

Locations:

  • Liverpool Hospital
  • Liverpool New South Wales 2170 Australia
  • St Vincent's Hospital
  • Sydney New South Wales 2010 Australia
  • Royal North Shore Hospital
  • Sydney New South Wales 2065 Australia
  • Calvary Mater Newcastle Hospital
  • Waratah New South Wales 2298 Australia
  • Royal Brisbane and Womens Hospital
  • Brisbane Queensland 4029 Australia
  • Royal Adelaide Hospital
  • Adelaide South Australia 5000 Australia
  • Peter MacCallum Cancer Centre
  • Melbourne Victoria 3008 Australia
  • Austin Hospital
  • Melbourne Victoria 3084 Australia
  • Monash Moorabbin Hospital
  • Moorabbin Victoria 3165 Australia
  • Fiona Stanley Hospital
  • Murdoch Western Australia 6450 Australia
  • Sir Charles Gairdner Hospital
  • Nedlands Western Australia 6009 Australia

View trial on ClinicalTrials.gov


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