This is an open-label, first-in-human, exploratory Phase 0 study evaluating the safety and diagnostic imaging performance of the DOTA-STR-17126 theranostic pair in patients with advanced or metastatic breast or prostate cancer. The study investigates \[68Ga\]Ga-DOTA-STR-17126 for PET imaging and, in patients with positive GRPR uptake, a low dose of \[177Lu\]Lu-DOTA-STR-17126 for SPECT imaging and dosimetry. The primary objective is to assess safety and tolerability. Secondary objectives include evaluation of imaging quality, biodistribution, pharmacokinetics, and radiation dosimetry. Exploratory objectives assess correlations between GRPR expression in tumour tissue and imaging uptake. The study is conducted at a single centre in Australia, with 12 evaluable participants (up to 20 enrolled), and supports the development of a GRPR-targeted theranostic approach for personalised cancer management.
This study is an open-label, first-in-human, exploratory Phase 0 clinical trial conducted at a single centre in Australia to characterise the safety profile, imaging performance, biodistribution, pharmacokinetics, and radiation dosimetry of the DOTA-STR-17126 theranostic pair in patients with advanced malignancy. The investigational approach uses a stepwise theranostic design in which all enrolled participants receive a single intravenous bolus administration of the GRPR-targeted PET radiopharmaceutical \[68Ga\]Ga-DOTA-STR-17126, followed by serial whole-body PET/CT imaging to evaluate tumour uptake and normal organ distribution. Participants demonstrating sufficient GRPR-positive tumour uptake on PET imaging may subsequently receive a single low-dose, slow intravenous infusion of \[177Lu\]Lu-DOTA-STR-17126, with serial planar and SPECT/CT imaging performed over several days to assess biodistribution and enable organ and tumour dosimetry calculations. Blood and urine samples are collected at predefined time points to support pharmacokinetic and radiation dosimetry analyses, alongside intensive clinical and laboratory safety monitoring. The study is exploratory in nature and is designed to optimise imaging protocols, generate human dosimetry data, and establish an initial safety and tolerability profile for this novel GRPR antagonist-based theranostic platform, thereby informing the design and dose selection for subsequent phase I/II clinical development.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
20
Participants will receive a low dose of \[177Lu\]Lu-DOTA-STR-17126, dose activity: 1.0+/-0.5 GBq (50 micrograms peptide) of \[177Lu\]Lu-DOTA-STR-17126 precursor will be administered as a slow infusion.
Participants will receive a single intravenous bolus dose of 150+/-50MBq (25 - 50 micrograms) of \[68Ga\]Ga-DOTA-STR-17126 precursor.
Icon Cancer Centre Hollywood
Perth, Western Australia, Australia
RECRUITINGNumber of participants with adverse events (AEs), serious adverse events (SAEs), with abnormal laboratory parameters (hematology, blood chemistry, and urinalysis), abnormal Physical examinations findings
1\. To evaluate adverse events (AEs) and serious adverse events (SAEs) by means of Common Toxicity Criteria Adverse Events (CTCAE version 5.0 Nov 2017); Assess occurrence and severity of AEs and SAEs; Monitor safety laboratory parameters (haematology, blood chemistry, and urinalysis) before, during and after IMP injections. The Common Terminology Criteria for Adverse Events (CTCAE) is a standardized, 1-5 severity grading system for classifying cancer treatment side effects (adverse events). Grades range from mild (1) to death (5). It is widely used in oncology to determine treatment safety, drug dosage modifications, and to document clinical trial toxicity
Time frame: Day 43
Standardized Uptake Value (SUV) of [⁶⁸Ga]Ga-DOTA-STR-17126
Calculation of Standardized Uptake Value (SUV) (max, mean, peak) \* between tumour and suitable reference organs (using liver parenchyma, lung parenchyma and mediastinal blood pool as reference regions) by PET/CT imaging, Higher numbers e.g., above 2.5 often highly suggestive of malignancy (cancerous growth. Lower numbers e.g., below 2.5 frequently indicate benign (non-cancerous) growths. SUVmax vs. SUVmean: A scan report will usually specify SUV\_max as the highest, most active single point in the tumor or SUV\_mean (the average activity across the entire tumor.
Time frame: Day 2 post-dose
PET/CT image quality of [⁶⁸Ga]Ga-DOTA-STR-17126
Qualitative assessment of PET/CT image quality using a 5-point scale from excellent to poor image, with parameters such as intensity, sharpness, noise of tumour uptake related to reference regions.
Time frame: Day 2 post-dose
Tumour to Background Ratio (TBR) of [⁶⁸Ga]Ga-DOTA-STR-17126
The ability to confirm preferential accumulation of \[68Ga\] Ga-DOTA-STR-17126 in target lesions and comparable detectability of tumour lesions by PET/CT, taking also into account the extent of uptake in non-target normal organs, and establish intra-participant image quality protocol. • Tumour to Background Ratio (TBR). High TBR: Indicates a "hot" or very active tumor that is easy to distinguish from the surrounding healthy tissue (e.g., a TBR of 3.0 or higher). Low TBR: Indicates that the tumor looks very similar to the surrounding background tissue, which can make it difficult to identify or measure accurately.
Time frame: Day 2 post-dose
Concentration of [68Ga]Ga-DOTA-STR-17126 and [177Lu]Lu-DOTA-STR-17126
Calculate concentration of \[68Ga\]Ga-DOTA-STR-17126 and of \[177Lu\]Lu-DOTA-STR-17126 in blood by counting radioactivity in respective samples at specific time intervals (radio-PK)
Time frame: Day 1 post-dose, Day 2, Day 4, Day 8
Percentage of injected activity (%IA) in tumour and non-tumour organs
Calculate retention pattern within body and blood pool by the percentage of injected activity (%IA) in tumour and non-tumour organs
Time frame: Day 1 post-dose, Day 2, Day 4, Day 8
Calculation of absorbed dose (AD, mGy/MBq)
Calculation of absorbed dose (AD, mGy/MBq) and effective whole-body dose (ED, mSv/MBq) of \[68Ga\]Ga-DOTA-STR-17126 and \[177Lu\]Lu-DOTA-STR-17126 The dosimetry analysis will enable estimated radiation absorbed doses from the radioligand therapeutic drug candidate \[177Lu\]Lu-DOTA-STR-17126 in organs and tumour lesions per unit administered activity (Gy/GBq).
Time frame: Day 1 post-dose
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