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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06520345




Registration number
NCT06520345
Ethics application status
Date submitted
12/07/2024
Date registered
25/07/2024
Date last updated
6/11/2024

Titles & IDs
Public title
The Study of 177Lu-TLX591 Plus SOC Versus SOC Alone in Patients With mCRPC (ProstACT GLOBAL)
Scientific title
A Multinational, Multicenter, Prospective, Randomized, Controlled, Open-Label, Phase 3 Study of Lutetium (177Lu) Rosopatamab Tetraxetan in Combination With Standard of Care Versus Standard of Care Alone in Patients With PSMA Positive Metastatic Castration-Resistant Prostate Cancer Previously After Androgen Receptor Pathway Inhibitor Treatment
Secondary ID [1] 0 0
177Lu-TLX591-203
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Castration-resistant Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 177Lu-TLX591
Treatment: Drugs - Enzalutamide
Treatment: Drugs - Abiraterone
Treatment: Drugs - Docetaxel

Experimental: 177Lu-TLX591 + Enzalutamide or Abiraterone or Docetaxel - Lutetium (177Lu) rosopatamab tetraxetan (177Lu-TLX591) 76 mCi (±10%) given approximately 14 days apart, plus SOC.

SOC is either:

Concurrent enzalutamide (starting dose 160 mg daily) + prednisone / prednisolone (5 mg twice a day) or equivalent.

or

Concurrent 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)

or

Sequential 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.

Active comparator: Control Arm (Enzalutamide or Abiraterone or Docetaxel) - SOC is either:

Enzalutamide (starting dose 160 mg daily) + prednisone / prednisolone (5 mg twice a day) or equivalent.

or

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)

or

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


Treatment: Drugs: 177Lu-TLX591
Participants randomized to Group A will receive two 76 mCi (±10%) doses of 177Lu-TLX591 14 days apart

Treatment: Drugs: Enzalutamide
Enzalutamide (starting dose 160 mg daily) + prednisone / prednisolone (5 mg twice a day) or equivalent.

Treatment: Drugs: Abiraterone
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)

Treatment: Drugs: Docetaxel
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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Radiographic Progression-free Survival
Timepoint [1] 0 0
337days
Secondary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
5 years
Secondary outcome [2] 0 0
Objective Response Rate (ORR)
Timepoint [2] 0 0
337days
Secondary outcome [3] 0 0
Time to a first symptomatic skeletal event (SSE)
Timepoint [3] 0 0
337days

Eligibility
Key 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) ].
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/07/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2030
Actual
Sample size
Target
430
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Westmead Hospital - Sydney
Recruitment hospital [2] 0 0
Nepean Hospital - Sydney
Recruitment hospital [3] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [4] 0 0
Australian Prostate Centre - Melbourne
Recruitment hospital [5] 0 0
GenesisCare Murdoch - Perth
Recruitment postcode(s) [1] 0 0
2143 - Sydney
Recruitment postcode(s) [2] 0 0
2747 - Sydney
Recruitment postcode(s) [3] 0 0
2500 - Wollongong
Recruitment postcode(s) [4] 0 0
3051 - Melbourne
Recruitment postcode(s) [5] 0 0
6150 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Nebraska

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Telix Pharmaceuticals (Innovations) Pty Limited
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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
Trial website
https://clinicaltrials.gov/study/NCT06520345
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06520345