Trial Title:
The Study of 177Lu-TLX591 Plus SOC Versus SOC Alone in Patients With mCRPC (ProstACT GLOBAL)
NCT ID:
NCT06520345
Condition:
Metastatic Castration-resistant Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Docetaxel
Conditions: Keywords:
Radiographic Progression Free Survival
Overall Survival
ARPI
Docetaxel
Prostate Cancer
Radionuclide therapy
TLX591
ProstACT-GLOBAL
PSMA
mCRPC
177Lu-TLX591
Radiologand therapy
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
This is a multinational, multicenter, prospective, randomized, controlled, open-label
Phase 3 study designed to investigate and confirm the benefits and risks associated with
177Lu-TLX591 administered together with SOC compared to SOC alone, in participants with
PSMA-positive metastatic castration resistant prostate cancer (mCRPC) who have progressed
after their first treatment with an ARPI (specifically abiraterone or enzalutamide) or
docetaxel administered during either the metastatic castrate-sensitive prostate cancer
(mCSPC) or first-line metastatic castrate-resistant prostate cancer (mCRPC) treatment
stages.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
177Lu-TLX591
Description:
Participants randomized to Group A will receive two 76 mCi (±10%) doses of 177Lu-TLX591
14 days apart
Arm group label:
177Lu-TLX591 + Enzalutamide or Abiraterone or Docetaxel
Other name:
Lutetium (177Lu) rosopatamab tetraxetan
Intervention type:
Drug
Intervention name:
Enzalutamide
Description:
Enzalutamide (starting dose 160 mg daily) + prednisone / prednisolone (5 mg twice a day)
or equivalent.
Arm group label:
177Lu-TLX591 + Enzalutamide or Abiraterone or Docetaxel
Arm group label:
Control Arm (Enzalutamide or Abiraterone or Docetaxel)
Intervention type:
Drug
Intervention name:
Abiraterone
Description:
Abiraterone (starting dose 1,000 mg daily) + prednisone / prednisolone (5 mg once daily
for the standard formulation), methylprednisolone (4 mg twice daily for the fine particle
formulation) or dexamethasone (1 mg once daily)
Arm group label:
177Lu-TLX591 + Enzalutamide or Abiraterone or Docetaxel
Arm group label:
Control Arm (Enzalutamide or Abiraterone or Docetaxel)
Intervention type:
Drug
Intervention name:
Docetaxel
Description:
Docetaxel: Single agent chemotherapy will consist of docetaxel given at a recommended
dose of 75mg/m2 IV every 3 weeks given in combination with oral prednisone / prednisolone
(5mg twice a day) or equivalent for up to 10 cycles
Arm group label:
177Lu-TLX591 + Enzalutamide or Abiraterone or Docetaxel
Arm group label:
Control Arm (Enzalutamide or Abiraterone or Docetaxel)
Summary:
The purpose of this study is to evaluate the efficacy and safety of 177Lu-TLX591 in
patients with metastatic castration-resistant prostate cancer who have progressed
following treatment with Androgen Receptor Pathway Inhibitor Treatment
Detailed description:
The primary objective of the study is to compare radiographic progression-free survival
(rPFS) in participants who receive 177Lu-TLX591 with SOC to rPFS in participants who
receive SOC only.
This study consists of three Parts:
- Part 1: Safety and Dosimetry Lead-in,
- Part 2: Randomized Treatment Expansion, and
- Part 3: Long-term Follow-up
The study will commence with a 30-patient safety and dosimetry lead-in (Part 1) and
proceed to a randomization treatment expansion in approximately 400 patients (Part 2).
Patients in Part 2 will be randomized in a 2:1 ratio to receive either 177Lu-TLX591 +
Standard of Care SoC (Group A), or SoC alone (Arm B).
SoC in this trial is either: ARPI (enzalutamide or abiraterone) or docetaxel.
All patients will be followed in long-term follow-up for at least 5 years from the first
therapeutic dose, death, or loss to follow up (Part 3).
Only patients that meet PSMA-positivity criteria per Blinded Independent Central Review
(BICR) will be eligible for this study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Be a male, at least 18 years old, with documented adenocarcinoma of the prostate
defined by histological / pathological confirmation.
- Be of ECOG Performance Status 0, 1, or 2 and have an estimated life expectancy of ≥6
months from Day 1.
- Have metastatic disease (defined as ≥1 metastatic lesion present on baseline CT, MRI
or bone scintigraphy).
- Have castration-resistant PC (defined as disease progressing despite castration by
orchiectomy or ongoing use of luteinizing hormone-releasing hormone [LHRH]
analogues) and must have a castrate level of serum/plasma testosterone (<50 ng/dL or
<1.7 nmol/L) at Screening
- Must have received a minimum of 12 weeks of prior therapy on their first ARPI
(abiraterone or enzalutamide), received in either mCSPC (de novo or recurrent) or
first-line mCRPC treatment setting. Participants may have received docetaxel in the
mCSPC setting following the CHARTERED or STAMPEDE treatment regimens (6 cycles of
docetaxel every 3 weeks) provided the last dose of therapy was ≥6 months prior to
screening and ≥4 cycles were administered.
- Have a disease that is progressing at study entry, despite a castrate testosterone
level (<50 ng/dL or <1.7 nmol/L), by the demonstration of at least one of the
following:
- Two consecutive rising PSA values assessed sequentially at least one week apart,
with the final measurement required to be a minimum of 2.0 ng/mL for study entry.
Only the last measurement must meet or exceed 2.0 ng/mL.
- Progressive disease or new lesion(s) in the viscera or lymph nodes as per RECIST1.1
or in bone as per PCWG3. Any ambiguous results are to be confirmed by other imaging
modalities (e.g., CT or MRI scan).
- Have disease that is PSMA-positive, as demonstrated by a 68Ga-PSMA-11 PET/CT or
PET/MRI scan and confirmed as eligible by the Sponsor's appointed BICR.
- Must have recovered to ≤ Grade 1 from all clinically significant toxicities related
to prior therapies (i.e., surgery, local radiotherapy, ARPI, chemotherapy, etc.)
with the exception of alopecia. Specific conditions may be discussed with the
medical monitor as needed.
- Have adequate organ function at Screening:
Bone marrow:
- Platelets ≥150×109/L.
- Absolute neutrophil count ≥2×109/L.
- Hemoglobin >10g/dL (with no red blood cell transfusion in the previous 4 weeks).
- Lymphocyte count >1.0x109/L
Liver function:
- Total bilirubin ≤ 1.5× the upper limit of normal (ULN). For participants with known
Gilbert's Syndrome ≥3× ULN is permitted.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3× ULN.
Renal function:
- Creatinine clearance ≥45 mL/min determined using the Cockcroft-Gault formula.
- Have the capacity to understand the study and be able and willing to comply with all
protocol requirements.
- Participants must comply with the radiation protection rules (including hospital
admissions and isolation) that are used by the treating institution in order to
protect their contacts and the general public, especially if a female partner of the
participant is or could be pregnant.
- Must agree to practice adequate precautions to prevent pregnancy in a partner and to
avoid potential problems associated with radiation exposure to the unborn child
(Recommendations related to contraception and pregnancy testing in clinical trials
Version 1.1, [CTFG (Clinical Trial Facilitation Group), 2020) ].
Exclusion Criteria:
- Is unable to understand or is unwilling to sign a written informed consent document
or to follow investigational procedures in the opinion of the Investigator.
- Has PC associated with pathological findings consistent with small cell or any
histology other than adenocarcinoma of the prostate. If there are minor (<20%)
elements of neuroendocrine histology, this is acceptable.
- Diagnosed with other malignancies that are expected to alter life expectancy or may
interfere with disease assessment. However, participants with a prior history of
malignancy that has been adequately treated and who have been disease-free for more
than 3 years are eligible, as are participants with adequately treated non-melanoma
skin cancer, and superficial bladder cancer.
- Is at increased risk of hemorrhage or bleeding, or with a recent history (within the
last 6 months) of a thromboembolic event (e.g., deep vein thrombosis [DVT] /
pulmonary embolism [PE]) and have been administered long-term anti-coagulant or
anti-platelet agents, with the exception of low dose aspirin (75 to 100 mg daily).
- Has received prior treatment with monoclonal antibody (mAb) J591 or HuJ591 or any
other PSMA targeted therapy.
- Have received chemotherapy in the mCRPC or non-metastatic prostate cancer (nmCRPC)
settings (note: prior docetaxel use in the mCSPC setting with CHAATERED or STAMPEDE
regimens is permitted if the last dose of therapy was ≥6 months prior to screening
and ≥4 cycles of docetaxel were administered).
- Has known allergies, hypersensitivity, or intolerance to the investigational drug or
its excipients.
- Has received prior systemic anti-cancer therapy (e.g., chemotherapy, immunotherapy,
or biological therapy) and/or radiation therapy within 4 weeks of enrolment
(excluding ARPI and/or LHRH analogues).
OR if any significant AEs have not resolved to National Cancer Institute (NCI) AE
Criteria ≤ 2.
OR are receiving other concurrent cytotoxic chemotherapy, immunotherapy, radioligand
therapy, or investigational therapy.
- Has received prior treatment with radioisotopes, including but not limited to:
89Strontium, 153Samarium, 186Rhenium, 188Rhenium, 223Radium, or hemi-body
irradiation within 6 months prior to enrolment.
- Has received other investigational therapy within 4 weeks of enrolment.
- Has known brain metastases with long-axis ≥1cm, or liver metastases with long-axis
≥1cm, or lytic bone metastases with long-axis ≥1cm.
- Has a history of seizure and/or stroke within the past 6 months. Has clinical or
radiologic findings indicative of impending spinal cord compression or experience
symptomatic spinal cord compression.
- Has evidence of a serious active or sub-clinical infection or angina pectoris (New
York Heart Association [NYHA] Class III or IV), significantly prolonged QT interval
or other serious illness(es) involving the cardiac, respiratory, central nervous
system, renal, hepatic or hematological organ systems, that might impair the ability
to complete this study or could interfere with determination of causality of any
adverse effects experienced in this study, or which require treatment that could
interact with study treatment, particularly with enzalutamide.
- Has received treatment with any PARP inhibitors (i.e., Olaparib) or with any
platinum based anti-neoplastic drugs.
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Biogenix Molecular LLC
Address:
City:
Miami
Zip:
33165
Country:
United States
Status:
Recruiting
Contact:
Last name:
Dr. Almaguel
Phone:
786-791-1799
Email:
falmaguelmd@cira-health.com
Investigator:
Last name:
Dr. Almaguel
Email:
Principal Investigator
Facility:
Name:
XCancer Omaha
Address:
City:
Omaha
Zip:
68130
Country:
United States
Status:
Recruiting
Contact:
Last name:
Tony Romero
Phone:
402-697-2229
Email:
tony@xcancer.com
Investigator:
Last name:
Dr. Nordquist
Email:
Principal Investigator
Facility:
Name:
Westmead Hospital
Address:
City:
Sydney
Zip:
2143
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Westmead Hospital
Phone:
+61 2 8890 5200
Email:
wslhd-cpmcc-enquiries@health.nsw.gov.au
Contact backup:
Last name:
Study Coordinator
Phone:
+61 2 8890 8383
Investigator:
Last name:
Dr Tania Moujaber
Email:
Principal Investigator
Facility:
Name:
Nepean Hospital
Address:
City:
Sydney
Zip:
2747
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
+61 2 4734 2156
Email:
Nbmlhd-nm-research@health.nsw.gov.au
Investigator:
Last name:
Dr. Veronica Wong
Email:
Principal Investigator
Facility:
Name:
Wollongong Hospital
Address:
City:
Wollongong
Zip:
2500
Country:
Australia
Status:
Not yet recruiting
Contact:
Last name:
Carly Leighton
Phone:
+61 2 4222 5200
Email:
ISLHD-CancerClinicalTrials@health.nsw.gov.au
Investigator:
Last name:
Dr Gary Tincknell
Email:
Principal Investigator
Facility:
Name:
Australian Prostate Centre
Address:
City:
Melbourne
Zip:
3051
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Prof Tony Costello
Phone:
+61 3 8373 7600
Email:
info@apcr.org.au
Investigator:
Last name:
Prof. Tony Prof Costello
Email:
Principal Investigator
Facility:
Name:
GenesisCare Murdoch
Address:
City:
Perth
Zip:
6150
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
+61 8 9366 1500
Email:
kate.waswo@genesiscare.com
Investigator:
Last name:
Dr. Aviral Singh
Email:
Principal Investigator
Start date:
July 26, 2024
Completion date:
December 2030
Lead sponsor:
Agency:
Telix Pharmaceuticals (Innovations) Pty Limited
Agency class:
Industry
Source:
Telix Pharmaceuticals (Innovations) Pty Limited
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06520345
