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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04876651




Registration number
NCT04876651
Ethics application status
Date submitted
3/05/2021
Date registered
6/05/2021

Titles & IDs
Public title
The Present Study Aims to Compare Patients Who Receive the Investigational Product (177Lu-DOTA-rosopatamab) Plus Standard of Care, in Comparison to Standard of Care Only
Scientific title
A Multinational, Multicenter, Prospective, Randomized, Controlled, Open Label Phase 3 Study With Best Standard of Care With and Without 177Lu-DOTA-rosopatamab for Patients With PSMA Expressing Metastatic Castration-resistant Prostate Cancer Progressing Despite Prior Treatment With a Novel Androgen Axis Drug
Secondary ID [1] 0 0
177Lu-TLX591-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - 177Lu-DOTA-rosopatamb
Treatment: Drugs - Standard of Care

Experimental: Group A - Two single intravenous (IV) injections of 76 mCi each (equivalent to a 45 mCi/m2 dose in a standard 1.7m2 individual) of 177Lu-DOTA- rosopatamab, given 14 days apart, plus best Standard of Care

Active comparator: Group B - Participants will receive the Standard of Care

Experimental: Biodistribution and Dosimetry Sub-Study - Two single intravenous (IV) injections of 76 mCi each (equivalent to a 45 mCi/m2 dose in a standard 1.7m2 individual) of 177Lu-DOTA- rosopatamab, given 14 days apart, plus best Standard of Care


Other interventions: 177Lu-DOTA-rosopatamb
Two single intravenous (IV) injections of 76 mCi each (equivalent to a 45 mCi/m2 dose in a standard 1.7m2 individual) of 177Lu-DOTA- rosopatamab, given 14 days apart, plus best SoC

Treatment: Drugs: Standard of Care
enzalutamide or abiraterone \[+ prednisone/prednisolone)\] or docetaxel

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Comparison of radiographic progression-free survival (rPFS)
Timepoint [1] 0 0
Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [1] 0 0
Overall survival
Timepoint [1] 0 0
Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [2] 0 0
Tumour objective response rate (ORR)
Timepoint [2] 0 0
Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [3] 0 0
Time to a first Symptomatic Skeletal Event (SSE)
Timepoint [3] 0 0
Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [4] 0 0
Progression-free survival
Timepoint [4] 0 0
Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [5] 0 0
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Timepoint [5] 0 0
Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [6] 0 0
Adverse events of special interest (AESI)
Timepoint [6] 0 0
Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [7] 0 0
Health-related quality of life by ECOG
Timepoint [7] 0 0
Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [8] 0 0
Health-related quality of life by FACT-P
Timepoint [8] 0 0
Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [9] 0 0
Health-related quality of life by BPI-SF
Timepoint [9] 0 0
Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [10] 0 0
Health-related quality of life by EQ-5D-5L
Timepoint [10] 0 0
Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [11] 0 0
Health-related quality of life by EORTC/QQ-C30
Timepoint [11] 0 0
Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [12] 0 0
Assessment of changes in prostate specific antigen (PSA)
Timepoint [12] 0 0
Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [13] 0 0
Time to radiographic soft tissue progression (TTSTP)
Timepoint [13] 0 0
Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [14] 0 0
Biochemical response as indicated by PSA levels, lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) levels
Timepoint [14] 0 0
Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [15] 0 0
Development of anti-drug antibodies (ADA) to 177Lu-DOTA-TLX591
Timepoint [15] 0 0
Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [16] 0 0
Titer of anti-drug antibodies (ADA) to 177Lu-DOTA-TLX591
Timepoint [16] 0 0
Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [17] 0 0
Duration of positiveness in the development of anti-drug antibodies (ADA) to 177Lu-DOTA-TLX591
Timepoint [17] 0 0
Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [18] 0 0
Neutralizing anti-drug antibodies (NAb) to 177Lu-DOTA-TLX591
Timepoint [18] 0 0
Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [19] 0 0
To determine whole body biodistribution (BD) of administered activity 177Lu-DOTATLX591(m17)
Timepoint [19] 0 0
Day 1 to day 23 after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [20] 0 0
To determine organ radiation dosimetry of tracer levels of administered activity 177Lu-DOTATLX591(m17)
Timepoint [20] 0 0
Day 1 to day 23 after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [21] 0 0
To determine pharmacokinetics (PK) of administered activity 177Lu-DOTATLX591
Timepoint [21] 0 0
Day 1 to day 23 after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [22] 0 0
Demonstrate comparability of whole body biodistribution dosimetry of the 177Lu-DOTA-TLX591
Timepoint [22] 0 0
Day 1 to day 23 after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [23] 0 0
Demonstrate comparability of organ uptake dosimetry of the 177Lu-DOTA-TLX591
Timepoint [23] 0 0
Day 1 to day 23 after two administrations of 177Lu-DOTA-rosopatamab
Secondary outcome [24] 0 0
Demonstrate organ radiation dosimetry comparability of the 177Lu-DOTA-TLX591
Timepoint [24] 0 0
Day 1 to day 23 after two administrations of 177Lu-DOTA-rosopatamab

Eligibility
Key inclusion criteria
1. Be a male, at least 18 years old, with metastatic adenocarcinoma of the prostate defined by histological / pathological confirmation of PC.
2. Be of ECOG Performance Status 0, 1, or 2 and have an estimated life expectancy of =6 months.
3. Have metastatic disease (=1 metastatic lesions present on baseline CT, MRI, or bone scan imaging).
4. Have castration-resistant PC (defined as disease progressing despite castration by orchiectomy or ongoing use of luteinizing hormone-releasing hormone [LHRH]) and must have a castrate level of serum/plasma testosterone (<50 ng/dL or <1.7 nmol/L).
5. In the mCRPC setting, must have received a minimum of 12 weeks of prior therapy with a NAAD, either enzalutamide or abiraterone plus prednisone.
6. Should have received one line of prior taxane therapy or have refused or be ineligible for taxanes
7. 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:

1. Rising PSA values done in sequence at least 1 week apart and with a minimal starting value of 2.0 ng/mL.
2. Progressive disease or new lesion(s) in the viscera or lymph nodes as per RECIST1.1 or in bone as per Prostate Cancer Working Group 3 [PCWG3; Scher et al., 2016]). Any ambiguous results are to be confirmed by other imaging modality (e.g., CT or MRI scan).
8. Have disease that is PSMA positive, as demonstrated by a 68Ga-PSMA11 PET/CT scan and confirmed as eligible by the Sponsor's central reader (patient must have at least one site of metastatic disease with SUVmax =1.5 times the SUV of normal liver). If the disease meets the criteria for PSMA positivity, but there is one or more soft tissue lesion of = 2 cm that is not PSMA positive, then the patient is to be excluded on the grounds that there is substantial disease which might not respond to the therapy.
9. Must have recovered to = Grade 2 from all clinically significant toxicities related to prior therapies (i.e., surgery, local radiotherapy, NAAD, chemotherapy, etc.).
10. Can be receiving a bisphosphonate or denosumab regimen provided that the patient has been receiving and tolerating this treatment for =30 days prior to randomization.
11. Have adequate organ function at Screening:

a. Bone marrow: i. Platelets =150×109/L. ii. Absolute neutrophil count >1.5×109/L. iii. Hemoglobin =10g/dL (no red blood cell transfusion in the previous 4 weeks).

b. Liver function: i. Total bilirubin < 1.5×the upper limit of normal (ULN). For patients with known Gilbert's Syndrome <3×ULN is permitted. ii. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <3×ULN OR <5×ULN for patients with liver metastases. c. Renal function: i. Serum/plasma creatinine <1.5×ULN or creatinine clearance =50 mL/min determined using the Cockcroft & Gault formula.
12. Have the capacity to understand the study and be able and willing to comply with all protocol requirements.
13. Patients 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 patient is or could be pregnant.
14. 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 (Refer to Clinical Trials Facilitation Group, 2020: Recommendations related to contraception and pregnancy testing in clinical trials Version 1.1, CTFG, 2020).
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Are unable to understand or are unwilling to sign a written informed consent document or to follow investigational procedures in the opinion of the Investigator.
2. Have PC associated with pathological findings consistent with small cell or any histology other than adenocarcinoma of the prostate. If there are minor elements of neuroendocrine histology, this is acceptable.
3. Uncontrolled pain.
4. Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, patients 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 patients with adequately treated non-melanoma skin cancer, and superficial bladder cancer.
5. Are at increased risk of hemorrhage or bleeding, or with a recent history of a thrombolytic event (e.g., deep vein thrombosis [DVT]/ pulmonary embolism [PE]) and have been administered long-term anti-coagulant or anti-platelet agents.
6. Have received prior treatment with monoclonal antibody (mAb) J591 or HuJ591 or any other PSMA targeted therapy.
7. Have known allergies, hypersensitivity, or intolerance to the investigational drug or its excipients.
8. Have received prior systemic anti-cancer therapy (e.g., chemotherapy, immunotherapy, or biological therapy) and/or radiation therapy within 4 weeks of randomization 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.
9. Have received prior treatment with radioisotopes, including but not limited to: 89Strontium, 153Samarium, 186Rhenium, 188Rhenium, 223Radium, or hemi-body irradiation within 6 months prior to randomization.
10. Have received other investigational therapy within 4 weeks of randomization.
11. Have known brain metastases or hepatic metastases.
12. Have a history of seizure and/or stroke within past 6 months.
13. Have clinical or radiologic findings indicative of impending cord compression or experience symptomatic cord compression.
14. Have 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, which 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.
15. Have received treatment with any PARP inhibitors (i.e., Olaparib) or with any platinum based anti-neoplastic drugs.
16. Have a known alteration in breast cancer genes (BRCA) BRCA1, BRCA2, or Ataxia Telangiectasia Mutated Gene (ATM) gene and are eligible to receive Olaparib therapy according to their institution's SoC

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Westmead Hospital - Westmead
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 0 0
Monash Health - Clayton
Recruitment hospital [4] 0 0
Austin Health - Melbourne
Recruitment hospital [5] 0 0
'GenesisCare Murdoch' - Murdoch
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3083 - Melbourne
Recruitment postcode(s) [5] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Brenda Cerqueira, M.Sc
Address 0 0
Country 0 0
Phone 0 0
+61 83180090
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.