In Men With Metastatic Prostate Cancer, What is the Safety and Benefit of Lutetium-177 PSMA Radionuclide Treatment in Addition to Chemotherapy

Phase 2

Active, not recruiting

• Conditions: Metastatic Hormone Naive Prostate Cancer
• Interventions: Drug: 177Lu-PSMA-617; Drug: Docetaxel

• Registration Number: NCT04343885
• Lead Sponsor: Peter MacCallum Cancer Centre, Australia

Brief Summary

This phase 2 randomised clinical trial will compare the effectiveness of Lu-PSMA therapy followed by docetaxel chemotherapy versus docetaxel chemotherapy on its own in patients with newly-diagnosed high-volume metastatic hormone-naive prostate cancer (mHNPC).

Detailed Description

This is an open label, randomised, stratified, 2-Arm, multi-centre, phase 2 clinical trial recruiting 140 newly-diagnosed high-volume mHNPC patients at 11 Australian centres over a period of 18 months. Patients will be randomised to the experimental Arm (177Lu-PSMA followed by docetaxel) or standard-of-care Arm (docetaxel) in a 1:1 ratio. All patients will receive ADT continuously throughout the trial. Patients will be stratified according to disease volume by conventional imaging (low-volume vs. high-volume) and duration of ADT at time of registration (≤ 28 days vs. \> 28 days).

Study Timeline

• Study First Submitted: 2020-04-01
• Study First Submitted QC: 2020-04-09
• Study First Posted: 2020-04-13
• Study Start: 2020-04-21
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-03
• Last Update Posted: 2023-07-06
• Primary Completion: 2024-04
• Study Completion: 2024-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 130

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
177Lu-PSMA+ Docetaxel	Docetaxel	7.5 GBq (± 10%) 177Lu-PSMA every 6 weeks x 2 cycles. Docetaxel 75 mg/m2 commencing 6 weeks later, every 3 weeks x 6 cycles
Docetaxel (Control)	Docetaxel	Docetaxel 75 mg/m2 every 3 weeks x 6 cycles
177Lu-PSMA+ Docetaxel	177Lu-PSMA-617	7.5 GBq (± 10%) 177Lu-PSMA every 6 weeks x 2 cycles. Docetaxel 75 mg/m2 commencing 6 weeks later, every 3 weeks x 6 cycles

Primary Outcome Measures

Name	Time	Method
Undetectable prostate specific antigen (PSA) rate at 12 months after commencement of protocol therapy	Upto 32 months assuming 18 months to complete recruitment, a maximum of 1.6 months from consent to commencement of treatment for last patient and then 12 months from commencement of treatment for last patient.	Undetectable PSA is defined as PSA ≤ 0.2ng/ml at 12 months after protocol treatment commencement. Patients who experience unequivocal radiographic (by conventional imaging modality) and/or clinical disease progression within 12 months of initiating protocol treatment will be considered as not having undetectable PSA at 12 months.

Secondary Outcome Measures

Name	Time	Method
PSA-progression free survival (PSA-PFS) between treatment Arms	Through study completion, up until 2 years after the last patient commences treatment.	PSA progression is defined as a rise in PSA by more than 25% AND more than 2ng/mL above the nadir (lowest PSA point). This needs to be confirmed by a repeat PSA performed at least 3 weeks later. Early rises in PSA prior to 12 weeks will be disregarded in determining PSA progression. To be measured from the date of randomisation to the first date of evidence of PSA progression or date of death due to any cause.
Radiographic-PFS (rPFS) between treatment Arms	Through study completion, up until 2 years after the last patient commences treatment.	Radiographic progression will be assessed by the investigator per RECIST1.1 for soft tissue and PCWG3 for bone lesions. To be measured from randomisation to the first date of documented radiographic progression using conventional imaging or death due to any cause, whichever occurs first.
Describe and compare health-related QoL within 12 months of treatment commencement between treatment Arms	Through completion of 12 months after treatment commencement of last patient, maximum 32 months.	QoL will be assessed using the Functional Assessment of Cancer Therapy for Prostate Cancer (FACT-P) questionnaire. The primary endpoint for QoL is the area under the curve (AUC) of the trial outcome index (TOI).; QoL will be assessed at baseline, 6 weeks, 3 months, 6 months, 9 months and 12 months and will be scored according to the respective manuals.
Safety of 177Lu-PSMA followed by docetaxel compared to docetaxel alone	Through completion of treatment, maximum 26 months.	The type, grade and relationship to treatment of adverse events (AE) will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0
Time to development of castration resistance between treatment Arms	Through study completion, up until 2 years after the last patient commences treatment.	Castration resistance is defined as rising PSA and/or radiographic progression despite castrate levels of testosterone (≤ 50ng/dL or ≤ 1.73nmol/L).To be measured from the date of randomisation to the date of first evidence of castration resistance.
Overall survival (OS) between treatment Arms	Through study completion, up until 2 years after the last patient commences treatment.	OS is defined as the time from randomisation to the date of death due to any cause.
Early PSMA PET response between treatment Arms	Through completion of 3 months after treatment commencement for last patient, maximum 23 months.	PSMA PET response assessed 3 months after treatment commencement defined by central imaging review of 68Ga-PSMA PET CT images.
Describe and compare pain within 12 months of treatment commencement between treatment Arms	Through completion of 12 months after treatment commencement of last patient, maximum 32 months.	Pain will be assessed using the Brief Pain Inventory - Short Form (BPI-SF). The primary endpoint for pain is the area under the curve (AUC) of the worst pain in 24h.; Pain and QoL will be assessed at baseline, 6 weeks, 3 months, 6 months, 9 months and 12 months and will be scored according to the respective manuals.

Trial Locations

Locations (12)

Liverpool Hospital; 🇦🇺 Liverpool, New South Wales, Australia

St Vincent's Hospital Sydney; 🇦🇺 Sydney, New South Wales, Australia

Royal North Shore; 🇦🇺 St Leonards, New South Wales, Australia

Chris O'Brien Lifehouse; 🇦🇺 Sydney, New South Wales, Australia

Sir Charles Gairdner Hospital; 🇦🇺 Nedlands, Western Australia, Australia

Fiona Stanley Hospital; 🇦🇺 Murdoch, Western Australia, Australia

Peter MacCallum Cancer Centre; 🇦🇺 Melbourne, Victoria, Australia

Austin Health; 🇦🇺 Melbourne, Victoria, Australia

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

Royal Brisbane and Women's Hospital; 🇦🇺 Brisbane, Queensland, Australia

Cabrini Hospital; 🇦🇺 Malvern, Victoria, Australia

Alfred Hospital; 🇦🇺 Prahran, Victoria, Australia