177 LuPSMA-617 vs Docetaxel in Metastatic Castration Resistant and PSMA-Positive Prostate Cancer

A Randomized Phase II Study of 177 LuPSMA-617 vs Docetaxel in Patients With Metastatic Castration-Resistant Prostate Cancer and PSMA-Positive Disease

177Lu PSMA 617 is a new type of therapy which is designed to deliver high doses of radiation directly to prostate cancer sites in the body. The purpose of this study is to find out whether 177Lu PSMA 617can slow the growth of prostate cancer compared to standard chemotherapy treatment

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: 177Lu-PSMA-617; Drug: Docetaxel

Detailed Description

The standard or usual treatment for this disease is a chemotherapy drug called docetaxel, given by intravenous every 3 weeks, for up to 12 treatments.

177Lu-PSMA-617 is a new type of therapy for prostate cancer. Laboratory tests show that it may help slow the growth of prostate cancer. 177Lu-PSMA-617 has been shown to shrink tumours in animals and has been studied in limited numbers of men with prostate cancer and seems promising but it is not clear if it can offer better control of prostate cancer compared to docetaxel chemotherapy .

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA - Vancouver Cancer Centre
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Regional Cancer Program
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network
    • Toronto, Ontario, Canada, M4N 3M5
      • Odette Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • CHUM-Centre Hospitalier de l'Universite de Montreal
    • Montreal, Quebec, Canada, H3T 1E2
      • The Jewish General Hospital
    • Québec, Quebec, Canada, G1R 2J6
      • Hotel-Dieu de Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • CIUSSS de l'Estrie - Centre hospitalier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histological evidence of prostate cancer with no evidence of small cell component
• Patients must have castration resistance and metastatic disease with evidence of biochemical or imaging progression in the setting of surgical/medical castration
• Progression on treatment with abiraterone and/or enzalutamide, or similar next-generation androgen receptor (AR) targeted therapy
• Evidence of PSMA positive metastatic disease, as assessed on PSMA-PET imaging studies obtained as part of other clinical trial protocols are mandated, provided they are obtained within a timeframe that meets the requirements of this study. The radiopharmaceuticals must be based on a lysine-urea-glutamate backbone, with a 18F or 68Ga radionuclide label.
• Prior orchiectomy, or if on LHRH agonist/antagonist then testosterone < 1.7 nmol/L
• Adequate organ function
• Recover from all previous cancer treatment toxicities to grade ≤ 2 (as per CTCAE v5.0)
• Male subject ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Exclusion Criteria:

• Prior treatment with chemotherapy for castration-resistant disease or prior chemotherapy in the castration-sensitive (hormone-sensitive) setting ≤ 1 year prior to enrollment.
• Prior treatment with 177Lu-PSMA (including other radiolabeled therapeutic PSMA-ligands) or radio-immunotherapy. Prior treatment with radium-223 is allowed but requires a minimum of a 6-month interval between the last dose of radium-223 and enrollment.
• Radiotherapy to target lesions (measurable disease) ≤ 12 weeks prior to enrolment.
• Presence of majority (> 50% of extra-osseous lesions) or large (> 5 cm) soft tissue lesions that are negative on PSMA-Ligand PET/CT or PSMA-Ligand PET/MR
• Known parenchymal brain metastases
• Active epidural disease (treated epidural disease is permitted)
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Clinically significant cardiac disease
• Major surgery within 4 weeks of starting study treatment
• Patients with a history of hypersensitivity to the study drug or components
• Patients with a clinically significant medical condition which, in the opinion of the treating physician, makes it undesirable for the patient to participate in the study or which could jeopardize compliance with study requirements including, but not limited to: ongoing or active infection, significant uncontrolled hypertension, or sever psychiatric illness/social situations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Docetaxel	Drug: Docetaxel; 75mg/m2 IV every 3 weeks maximum 12 cycles
Experimental: 177 Lu-PSMA-617	Drug: 177Lu-PSMA-617; IA of 7.4GBq (± 10%) IV every 6 weeks; maximum 6 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		3 years
Progression-free survival rate at 6 months defined by PSA		6 months
Progression-free survival rate at 6 months defined by PCWG 3		6 months
Progression-free survival rate at 6 months defined by RECIST 1.1		6 months
Second rPFS in patients who meet the criteria for rPFS and cross over to the alternate therapy		3 years
Time to commencement of third line therapy		3 years
Proportions of patients with decreased PSA from baseline and the magnitude of change	e.g. ≥ 30%, ≥ 50%, ≥ 90% decline from baseline	3 years
Clinical benefit rate (CBR) > 24 weeks (RECIST v1.1).		3 years
Response duration including partial response, complete response or stable disease > 24 (RECIST v1.1)		3 years
Adverse event (AE) profile (CTCAE v5.0)		3 years

Collaborators and Investigators

• Sponsor: Canadian Cancer Trials Group
• Collaborators: Novartis Pharmaceuticals; Prostate Cancer Canada
• Investigators: Study Chair: Francois Benard, BCCA - Vancouver Cancer Centre, BC Canada; Study Chair: Fred Saad, CHUM-Centre Hospitalier de l'Universite de Montreal, Canada; Study Chair: Kim Chi, BCCA - Vancouver Cancer Centre, BC Canada

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2021
• Primary Completion (Actual): August 25, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 4, 2020
• First Submitted That Met QC Criteria: December 10, 2020
• First Posted (Actual): December 11, 2020

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: mCRPC; 177Lu-PSMA-617; docetaxel; metastatic prostate cancer; radioligand therapy
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Docetaxel; Pluvicto
• Other Study ID Numbers: PR21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Subject to CCTG Policy

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes