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Trial registered on ANZCTR


Registration number
ACTRN12623000216617
Ethics application status
Approved
Date submitted
17/02/2023
Date registered
28/02/2023
Date last updated
28/02/2023
Date data sharing statement initially provided
28/02/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Understanding the role of TLX591 in patients with metastatic Prostate cancer who failed 2 cycles of Lutetium PSMA therapy
Scientific title
A pilot, feasibility study of 177Lu-DOTA-Rosopatamab (TLX591) therapy in castrate resistant prostate adenocarcinoma patients showing progression on radioligand therapy using PSMA small molecule ligands
Secondary ID [1] 309016 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
RESCUE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Prostate Cancer 329064 0
Condition category
Condition code
Cancer 326044 326044 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The following procedures will be performed during the study, over the 10 visits at the clinic in the period of approximately 5 months:
o Patients will receive 2 doses of TLX591 2 weeks apart. Doses are administered intravenously over approximately 15 minutes. the dosage of the intravenous injections will be 76 mCi each. Patients will attend the PETCT department at Mercy Radiology to receive the therapy.
o Laboratory investigations (haematology, biochemistry, coagulation, and urinalysis).
o Measurement of vital signs (Blood pressure Measurement , respiratory rate, heart rate, and body temperature).
o Electrocardiogram
o Blood tests will be performed periodically after each therapy.
o During the months after therapy, we will contact patients to ask about their well-being, monitor any early or late symptoms or problems with therapy and ask to assess their pain.
o Imaging (68Ga-PSMA PET/CT and, if necessary 18FDG PET/CT], and whole-body CT.
68Ga-PSMA PET/CT will be conducted at screening and 35 days post 1 dose of TLX591.

Patients undergoing 68Ga-PSMA PET will receive both 68 GaPSMA tracer and contrast.
Typically they receive a dose of at least 110MBq of 68Ga-PSMA but no more than 250MBq. The dosage is decided based on clinical judgement of the radiologist. Where there is no contraindication patients will receive 50mls of Contrast 15 minutes before the scan then 90mls during the scan. The Contrast used is Omnipaque350.
If needed patients will also undergo 18FDG PET/CT. this would typically happen at screening, and it will depend on if the patients has had a scan done recently for their regular treatment.
They will receive between 220MBq and 350MBq of the tracer 18FDG. The dosage is decided based on weight. Patients Typically receive around 80 mls of Contrast.
We ask our patients to expect PET/CT appointments to last around 2.5 hours, however actual scan time is around 20 minutes.

o SPECT/CT scans will be performed after administration of the radioligand therapy, at one day, four days and seven days following each treatment to assess the dose of radiation delivered to the tumour. No tracer is administered for this scan. This appointment typically lasts 1hour.
Radiology technologists will perform all PET/CTs and SPECTs under the supervision of a radiologist. Images will be interpreted by 2 radiologists.

The Imaging tests are 68Ga-PSMA PET/CT, 18FDG PET/CT and SPECT/CT. They are all different types of scans that require patients to lay still on a bed while they go through the scanner. The length of time of when they are on the scanner varies as described above. However eligible patients will be familiar with these scans as they already had at least 2 cycles of a similar therapy called lutetium PSMA.

The first 2 patients will be enrolled at least 2 weeks apart and may be asked to have extra blood tests if clinically indicated

Participation in the trial will involve exposure to radiation for therapy and for imaging. The dose of radiation patients receive will be the same as the therapy dose delivered in other studies of this agent. Patients will be advised regarding the safety precautions required during the short time that they are radioactive.
There are risks involved with this type of radiation therapy to the function of your marrow, which makes blood cells and to kidney function. Patients are closely monitored for these effects and a a management plan is in place to treat/ minimize these effects.
The dose patients will receive will be the minimum dose required for an adequate treatment effect. This dose of radiation will mostly target tumour tissue.
Intervention code [1] 325460 0
Treatment: Other
Comparator / control treatment
No Control Group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 333901 0
To evaluate treatment response aided by PSA level results obtained via a blood test.
Timepoint [1] 333901 0
Patient's PSA levels will be obtained at Screening, day 14, day 28 and day 112 post dose 1.
Primary outcome [2] 333902 0
To evaluate the number of patients receiving one or two doses of therapy as per protocol.
This data will be obtained via audit of both patient study worksheet forms as well as IMP administration log.

Timepoint [2] 333902 0
end of recruitment
Primary outcome [3] 333903 0
To determine the safety and tolerability of 2 cycles of TLX591
Immediate safety assessment will take place via vital signs monitoring.
Vital signs monitoring will include measurements of pulse, blood pressure, respiratory rate, O2 saturation pre dosing and regularly after up until discharge. This will be done using an Eletronic Dinamap machine or manually if clinically indicated.
Patients will also undergo safety laboratory tests for longer term safety assessment. Safety laboratory tests will involve blood sampling and urine sampling. Safety laboratory tests will include serum samples for haematology, biochemistry, Liver Enzymes, Lactate dehydrogenase (LDH) and Biomarker analysis Serum PSA coagulation. We will also carry out a urinalysis of the patient's urine sample.

the rise or fall of the biomarker PSA will be used as an indication of treatment response.

A baseline ECG will be performed at screening and each dosing visit.
Timepoint [3] 333903 0
to be assessed after the first 2 patients are dosed at least 2 weeks apart and at each study visit via AE/SAE assessment until study completion.
Patients will also undergo other safety tests as per below:
Vital signs monitoring at screening and each dosing visit.
Safety blood tests will take place at day 11, day13, day 15, day 22 and day 28 post dose 1.
Patients showing signs of marrow suppression will require more regular monitoring as advised by the principal investigator.
Patients will also undergo ECG monitoring at screening and each dosing visit.
Secondary outcome [1] 418665 0
Recruitment rate and patient retention rate as determined by audits of recruitment logs.
Timepoint [1] 418665 0
When the last patient recruited completes the study
Secondary outcome [2] 418666 0
To evaluate the time needed for enrolling the target number of patients in the study. This will be achieved by audit of enrolment logs.
Timepoint [2] 418666 0
at the point of where the last patient is recruited
Secondary outcome [3] 418835 0
This a primary outcome.
Evaluation of patient perception of therapy benefits. This will be achieved by administration of Quality-of-life questionnaires.
The questionnaire used will be EQ5D-5L
Timepoint [3] 418835 0
This will take place during each patient visit from day 22 till day 112 post dose 1. There is a total of 4 visits in this period.

Eligibility
Key inclusion criteria
To qualify for enrolment, patients must meet the following criteria:
1. Ability to understand and sign an approved Informed Consent Form (ICF).
2. Ability to understand and comply with all protocol requirements.
3. Males at least 18 years of age and older.
4. ECOG performance status of 0 to 2.
5. Life expectancy greater than 6 months.
6. Patients must have histological, pathological, and/or cytological confirmation of prostate cancer.

7. Have metastatic disease (at least 1 metastatic lesion present at baseline CT, MRI, or bone scan imaging).
8. Patients must have prior orchiectomy and/or ongoing androgen-deprivation therapy.
9. Patients must have progressive Metastatic Castrate Resistant Prostate Cancer (mCRPC). Documented progressive mCRPC will be based on:
a. serum PSA progression defined as 2 consecutive increases in PSA from baseline of more than 25%, following a minimum of 2 cycles of radioligand therapy using PSMA small molecule ligands
b. appearance of two or more new lesions and/or increase of uptake or tumour PET volume greater than 30%
10. Have disease that is PSMA positive, as demonstrated by a 68Ga-PSMA PET/CT scan and without significant discordance at 18FDG PET/CT.
11. Must have recovered to at least Grade 2 from all clinically significant toxicities related to prior therapies (i.e., surgery, local radiotherapy, neoadjuvant androgen deprivation (NAAD), chemotherapy, etc.).
12. Can be receiving a bisphosphonate or denosumab regimen provided that the patient has been receiving and tolerating this treatment for at least 30 days prior to randomization.
13. Have adequate organ function at Screening, including bone marrow, liver and renal function.
a. Bone marrow: i. Platelets at least 150×109/L. ii. Absolute neutrophil count greater than 1.5×109/L. iii. Haemoglobin at least 10g/dL (no red blood cell transfusion in the previous 4 weeks).
b. Renal function: i. Serum/plasma creatinine less than 1.5×ULN or creatinine clearance equal to 50 mL/min determined using the Cockcroft & Gault formula.
c. Liver function: i. Total bilirubin less than 1.5×the upper limit of normal (ULN). For patients with known Gilbert's Syndrome less than 3×ULN is permitted. ii. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) less than 3×ULN OR less than 5×ULN for patients with liver metastases.
14. 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.
15. 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
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. Uncontrolled pain.
3. 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.
4. Are at increased risk of hemorrhage or bleeding, or with a recent history of a thrombotic event (e.g., deep vein thrombosis [DVT]/ pulmonary embolism [PE]) and have been administered long-term anti-coagulant or anti-platelet agents.
5. Have known allergies, hypersensitivity, or intolerance to the investigational drug or its excipients.
6. Have commenced any new systemic anti-cancer therapy since commencement of Lu-177-PSMA I&T therapy and recruitment or have any significant AE form previous therapy which have not resolved to National Cancer Institute (NCI) AE Criteria 2.
7. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy
8. Have received other investigational therapy within 4 weeks of treatment.
9. Previous Samarium, Strontium or Radium therapy.
10. Have a serious active or sub-clinical infection or heart failure (New York Heart Association [NYHA] Class III or IV), 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.
11. Have 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
Non-randomised 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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
No formal hypothesis is formulated for this pilot study. Data will be tabulated and aggregated. Frequency and cross tables will be used for descriptive analysis of the variables.

A total of 10 patients are planned to be enrolled in this pilot study. As this is a pilot study only, power has not been assessed. However, it would be expected that with 10 patients there should be enough numbers to determine the feasibility for a subsequent prospective hypothesis driven study

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
6/03/2023
Actual
Date of last participant enrolment
Anticipated
6/09/2023
Actual
Date of last data collection
Anticipated
26/02/2024
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment outside Australia
Country [1] 25273 0
New Zealand
State/province [1] 25273 0
Auckland

Funding & Sponsors
Funding source category [1] 313228 0
Commercial sector/Industry
Name [1] 313228 0
Telix Pharmaceuticals
Country [1] 313228 0
Australia
Primary sponsor type
Hospital
Name
Mercy Radiology
Address
100 Mountain Road
Epsom
Auckland
1023
Country
New Zealand
Secondary sponsor category [1] 314951 0
None
Name [1] 314951 0
Address [1] 314951 0
Country [1] 314951 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312458 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 312458 0
Ethics committee country [1] 312458 0
New Zealand
Date submitted for ethics approval [1] 312458 0
25/06/2022
Approval date [1] 312458 0
02/09/2022
Ethics approval number [1] 312458 0
: 2022 FULL 11944

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 124738 0
Dr Andrew Henderson
Address 124738 0
Mercy Radiology
PETCT
100 Mountain Road
Epsom
Auckland
1023
Country 124738 0
New Zealand
Phone 124738 0
+64 09 623 5857
Fax 124738 0
Email 124738 0
AHenderson@radiology.co.nz
Contact person for public queries
Name 124739 0
Rosane Joseph
Address 124739 0
Mercy Radiology
PETCT
100 Mountain Road
Epsom
Auckland
1023
Country 124739 0
New Zealand
Phone 124739 0
+64 096235862
Fax 124739 0
Email 124739 0
rjoseph@radiology.co.nz
Contact person for scientific queries
Name 124740 0
Rosane Joseph
Address 124740 0
Mercy Radiology
PETCT
100 Mountain Road
Epsom
Auckland
1023
Country 124740 0
New Zealand
Phone 124740 0
+64 096235862
Fax 124740 0
Email 124740 0
rjoseph@radiology.co.nz

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

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.