Clinical trial NCT04663997: 177 LuPSMA-617 vs Docetaxel in Metastatic Castration Resistant and PSMA-Positive Prostate Cancer
Official title: A Randomized Phase II Study of 177 LuPSMA-617 vs Docetaxel in Patients With Metastatic Castration-Resistant Prostate Cancer and PSMA-Positive Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: mCRPC
docetaxel
177Lu-PSMA-617
radioligand therapy
metastatic prostate cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: Prostate Cancer Canada
name: Novartis Pharmaceuticals
First posted: 2020-12-11
Enrollment: 200
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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 .

Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free survival
timeFrame: 3 years
Secondary outcomes:
measure: Progression-free survival rate at 6 months defined by PSA
timeFrame: 6 months
measure: Progression-free survival rate at 6 months defined by PCWG 3
timeFrame: 6 months
measure: Progression-free survival rate at 6 months defined by RECIST 1.1
timeFrame: 6 months
measure: Second rPFS in patients who meet the criteria for rPFS and cross over to the alternate therapy
timeFrame: 3 years
measure: Time to commencement of third line therapy
timeFrame: 3 years
measure: Overall Survival
timeFrame: 3 years
measure: Proportions of patients with decreased PSA from baseline and the magnitude of change
timeFrame: 3 years
measure: Clinical benefit rate (CBR) > 24 weeks (RECIST v1.1).
timeFrame: 3 years
measure: Response duration including partial response, complete response or stable disease > 24 (RECIST v1.1)
timeFrame: 3 years
measure: Adverse event (AE) profile (CTCAE v5.0)
timeFrame: 3 years
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montreal
country: Canada
facility: CHUM-Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Montreal
country: Canada
facility: The Jewish General Hospital
state: Quebec
city: Quebec City
country: Canada
facility: Hotel-Dieu de Quebec
state: Quebec
city: Sherbrooke
country: Canada
facility: CIUSSS de l'Estrie - Centre hospitalier
state: Quebec
Study officials:
affiliation: BCCA - Vancouver Cancer Centre, BC Canada
name: Kim Chi
role: STUDY_CHAIR
affiliation: BCCA - Vancouver Cancer Centre, BC Canada
name: Francois Benard
role: STUDY_CHAIR
affiliation: CHUM-Centre Hospitalier de l'Universite de Montreal, Canada
name: Fred Saad
role: STUDY_CHAIR
References: