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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04786847




Registration number
NCT04786847
Ethics application status
Date submitted
24/02/2021
Date registered
8/03/2021
Date last updated
12/02/2024

Titles & IDs
Public title
177Lu-DOTA-TLX591 Safety, Biodistribution and Dosimetry Study
Scientific title
A Phase 1 Safety, Tolerability, Biodistribution, Dosimetry and Efficacy Study of 177Lu-DOTA-TLX591 With Best Standard of Care in Patients With PSMA Expressing Metastatic Castration-resistant Prostate Cancer
Secondary ID [1] 0 0
177Lu-TLX591-001
Universal Trial Number (UTN)
Trial acronym
ProstACTSelect
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-TLX591

Experimental: Single administration of 177Lu-DOTA-TLX591 - Two single IV infusions of 76 mCi (2.8 GBq) each (equivalent to a 45 mCi/m2 administered activity in a standard 1.7m2 individual) of 177Lu-DOTA-TLX591, given 14 days apart. This therapy will be administered with the current standard of care treatment regimens.


Other interventions: 177Lu-DOTA-TLX591
TLX591, a monoclonal antibody HuX591 conjugated with a DOTA chelator and radiolabelled with 177Lu (177Lu-TLX591)
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0
Timepoint [1] 0 0
Day 1 to 5 years
Secondary outcome [1] 0 0
Whole body and organ uptake of 177Lu-DOTA-TLX591
Timepoint [1] 0 0
Day 1 to Day 15
Secondary outcome [2] 0 0
Compare the whole body and organ uptake of 177Lu-TLX591 and 68Ga-PSMA-11 radioactive tracers
Timepoint [2] 0 0
Day 1 to 15

Eligibility
Key inclusion criteria
- Be male, at least 18 years old, with histologically/pathologically confirmed
metastatic adenocarcinoma.

- Be of ECOG Performance Status 0, 1, or 2 and have an estimated life expectancy of = 6
months.

- Have metastatic disease (=1 metastatic lesions present on baseline whole body 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] agonists)
and must have a castrate level of serum/plasma testosterone (< 50 ng/dL or <1.7
nmol/L).

- In the mCRPC setting, must have received a minimum of 12 weeks of prior therapy with a
NAAD, either enzalutamide or abiraterone plus prednisone.

- Have received one line of prior taxane therapy, or have refused or are ineligible for
taxanes

- Have 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. Increase in PSA greater than 25% and > 2 ng/mL above nadir, confirmed by
progression at 2 timepoints at least 3 weeks apart.

2. Progressive disease or new lesion(s) (relative to previous imaging) in the
viscera or lymph nodes as per RECIST1.1 or in bone as per Prostate Cancer Working
Group 3 [PCWG3). Any ambiguous results are to be confirmed by additional imaging
modality (e.g., CT, Tc-99m bone scintigraphy)

- Have disease which is PSMA positive, as demonstrated by a 68Ga-PSMA-11 PET/CT or
[18F]DCFPyL PET/CT scan and confirmed as eligible by local 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.

- Must have recovered to = Grade 2 from all clinically significant toxicities related to
prior therapies (i.e., surgery, local radiotherapy, NAAD, chemotherapy, etc.).

- Can be receiving a bisphosphonate or denosumab regimen provided tolerance to this
therapy has been proven.

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

- Have the capacity to understand the study and be able and willing to comply with all
protocol requirements.

- Must comply with the radiation protection guidelines (including hospital admissions
and isolation) that are applied by the treating institution in order to protect their
contacts and the general public.

- 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
80 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion:

- Are unable, in the opinion of the Investigator, to understand or are unwilling to sign
a written informed consent document or to follow investigational procedures.

- Have PC 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.

- Experiencing uncontrolled pain

- Diagnosed with other malignancies that are expected to alter life expectancy or may
interfere with disease assessment. 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.

- At increased risk of hemorrhage, or with a recent history of a thrombotic event (e.g.,
deep vein thrombosis [DVT]/ pulmonary embolism [PE]) and/or are using long-term
anti-coagulant or anti-platelet agents.

- Have received prior administration of monoclonal antibody (mAb) J591 or HuJ591 or any
other PSMA targeted therapy.

- Have known allergies, hypersensitivity, or intolerance to the investigational drug or
its excipients.

- Have received systemic anti-cancer therapy (e.g., chemotherapy, immunotherapy, or
biological therapy) and/or radiation therapy within 4 weeks of enrollment 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.

- Have received prior treatment with radiopharmaceuticals containing, but not limited
to, the following radioisotopes: 89Strontium, 153Samarium, 186Rhenium, 188Rhenium,
223Radium; or have received hemi-body irradiation within 6 months prior to
randomization.

- Have received other investigational agents within 4 weeks of randomization.

- Have known brain metastases (any size) or hepatic metastases > 1 cm.

- Have a history of seizure and/or stroke within past 6 months.

- Have clinical or radiologic findings indicative of impending cord compression or
experiencing symptomatic cord compression.

- Have a serious active or sub-clinical infection, or angina pectoris or heart failure
(New York Heart Association [NYHA] Class III or IV), significantly prolonged QT
interval or other serious illness(es) involving the cardiac, respiratory, central
nervous, 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.

- Have received treatment with any PARP inhibitors (i.e., Olaparib) or with any platinum
based anti-neoplastic drugs.

- 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 treating institution SoC.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/01/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/09/2023
Sample size
Target
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
GatesheadWA
Recruitment hospital [1] 0 0
GenesisCare Newcastle - Newcastle
Recruitment hospital [2] 0 0
Diagnostic Nuclear Imaging at Hollywood Private Hospital - Perth
Recruitment hospital [3] 0 0
GenesisCare SJOg Medical Centre,Murdoch - Perth
Recruitment postcode(s) [1] 0 0
2290 - Newcastle
Recruitment postcode(s) [2] 0 0
6009 - Perth
Recruitment postcode(s) [3] 0 0
6150 - Perth

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1 trial of TLX591, a monoclonal antibody HuX591 conjugated with a DOTA
chelator and radiolabelled with 177Lu (177Lu-DOTA-TLX591). TLX591 is being developed as a
PSMA-targeting antibody to be radiolabelled with a therapeutic radiosotope for the treatment
of PSMA-expressing tumours, therefore this study has been designed to assess the safety and
tolerability, pharmacokinetics, whole body biodistribution and radiation dosimetry of
177Lu-DOTA-TLX591.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04786847
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/ct2/show/NCT04786847