Status:
ACTIVE_NOT_RECRUITING
Combination of Radium-223 and Lutetium-177 PSMA-I&T in Men with Metastatic Castration-Resistant Prostate Cancer
Lead Sponsor:
Peter MacCallum Cancer Centre, Australia
Conditions:
Metastatic Castration-resistant Prostate Cancer
MCRPC
Eligibility:
MALE
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
This clinical trial will evaluate the safety of Radium-223 in combination with 177Lu-PSMA-I\&T in metastatic castration-resistant prostate cancer: Phase I/II study
Detailed Description
This prospective, single-centre, single-arm, open label, phase I/II trial will assess and establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and recommended phase 2 dose (RP2...
Eligibility Criteria
Inclusion
- Patient must be ≥ 18 years of age and must have provided written informed consent.
- Histologically or cytologically confirmed adenocarcinoma of the prostate, OR unequivocal diagnosis of metastatic prostate cancer. (i.e. involving bone or pelvic lymph nodes or para-aortic lymph nodes) with an elevated serum PSA.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
- Patients must have progressed on ≥ 1 second-generation AR-targeted agent (e.g., enzalutamide, abiraterone, apalutamide, or darolutamide).
- Patients must have progressive disease for study entry. PCWG3 defines this as any one of the following:
- PSA progression: minimum of two rising PSA values from a baseline measurement with an interval of ≥ 1 week between each measurement.
- Soft tissue progression as per RECIST 1.1 criteria
- Bone progression: ≥ 2 new lesions on bone scan
- Symptomatic progression eg. Bone pain
- At least three weeks since receiving anti-cancer treatment (other than ADT), the completion of surgery or radiotherapy prior to registration.
- Prior surgical orchiectomy or chemical castration maintained on luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist).
- Serum testosterone levels ≤ 1.75nmol/L (≤ 50ng/dL) within 28 days before registration.
- Significant PSMA avidity on 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).
- ≥ 2 bone metastases must be present on bone scintigraphy which have not been previously treated with radiotherapy.
- No contraindication to treatment with a bone antiresorptive agent such as denosumab or zoledronic acid.
- Patients must have adequate bone marrow, hepatic and renal function documented within 28 days prior to registration, defined as:
- Haemoglobin ≥ 90 g/L independent of transfusions (no red blood cell transfusion in last four weeks)
- Absolute neutrophil count ≥ 1.5x10\^9/L
- Platelets ≥ 150 x10\^9/L
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome, where this applies for the unconjugated bilirubin component.
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN if there is no evidence of liver metastasis or ≤ 5 x ULN in the presence of liver metastases
- Albumin ≥ 25 g/L
- Adequate renal function: patients must have a creatinine clearance estimated of ≥ 40 mL/min using the Cockcroft Gault equation
- Sexually active patients are willing to use medically acceptable forms of barrier contraception.
- Willing to undergo biopsies, if disease is considered accessible and biopsy is feasible.
- Willing and able to comply with all study requirements, including all treatments and the timing and nature of all required assessments.
Exclusion
- Patients who meet any of the following criteria will be excluded from study entry:
- Superscan on Bone scan (WBBS) or diffuse marrow involvement on PSMA PET/CT
- Prior treatment with 223Ra or 177Lu-PSMA.
- Has received more than one previous line of chemotherapy for the treatment of metastatic prostate cancer.
- Sites of discordant FDG-positive disease defined by minimal PSMA-expression and no uptake on WBBS (for bone metastases).
- Other malignancies within the previous 2 years other than basal cell or squamous cell carcinomas of skin or other cancers that are unlikely to recur within 24 months.
- Symptomatic brain metastases or leptomeningeal metastases.
- Patients with symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable for ≥ four weeks.
- Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety.
Key Trial Info
Start Date :
September 13 2022
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 1 2026
Estimated Enrollment :
36 Patients enrolled
Trial Details
Trial ID
NCT05383079
Start Date
September 13 2022
End Date
December 1 2026
Last Update
February 7 2025
Active Locations (1)
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1
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia, 3000