Active Cancer, Cancer, GRPR-Targeted Molecular Imaging, Metastatic Breast Cancer, Metastatic Prostate Cancer, Radiopharmaceutical, Theranostic, Theranostic Radiopharmaceuticals
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUG[177Lu]Lu-DOTA-STR-17126
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.
DRUG[68Ga]Ga-DOTA-STR-17126
Participants will receive a single intravenous bolus dose of 150+/-50MBq (25 - 50 micrograms) of \[68Ga\]Ga-DOTA-STR-17126 precursor.
Sponsors
Integrated Haematology and Oncology Network
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
All participants are enrolled into one treatment/imaging group, with no control or comparison arm. Every participant follows the same study pathway (initial PET imaging with \[68Ga\]Ga-DOTA-STR-17126, with optional progression to low-dose \[177Lu\]Lu-DOTA-STR-17126 based on imaging findings), consistent with an open-label, non-randomised, single-arm, exploratory Phase 0 design.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion criteria refer to the enrolment of participants for the PET/CT and SPECT/CT imaging with the radioligands; PET imaging tracer \[68Ga\]Ga-DOTA-STR-17126 and with the SPECT imaging tracer \[177Lu\]Lu-DOTA-STR-17126. Participants must meet all of the following inclusion criteria to be eligible for enrolment. 1. Ability to understand and willingness to provide informed consent 2. Adults ≥ 18 years of age 3. Must have the following histologically or cytologically confirmed diagnosis of advanced or metastatic i. breast cancer ii. prostate cancer 4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 5. Participant must have clinical or radiological documented tumour progression as established by the Investigator within 30 days of signing consent for the study 6. Participants who have exhausted standard-of-care systemic therapies in their metastatic setting. At least one detectable by conventional imaging tumour lesion with any diameter of ≥ 1 cm in size 7. Participants must have adequate organ and bone marrow function, defined as follows: i. Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 ii. Platelet count ≥ 100,000/mm3 iii. Haemoglobin ≥ 9.0 g/dL iv. AST, ALT, alkaline phosphatase ≤ 3 times upper limit of normal (ULN) if there is no evidence of liver metastases or ≤5 ULN in the presence of liver metastases v. Total bilirubin ≤ 2 times upper limit of normal (ULN) vi. Creatinine ≤ 2 times ULN and creatinine clearance (CrCL) ≥ 60mL/min using the Cockcroft Gault equation (Appendix 2) 8. Able to remain still for up to 60 minutes per scan 9. Any other condition which, in the opinion of the Investigator, would preclude participation in this study Optional: Participants that have available archival tissue (at least 15 consecutive, unstained, formalin-fixed, paraffin embedded (FFPE) slides or 1 FFPE block), or a fresh tumour biopsy sample that opt to provide samples will be used for GRPR analysis (histology staining or RNA measurements). Participants without any archival tissue or fresh biopsy sample, or who refuse to provide archival tissue are still eligible for the study.
Exclusion criteria
Participants must not be enrolled into the trial if one or more of the following criteria are met. Participants must NOT meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events (AEs), serious adverse events (SAEs), with abnormal laboratory parameters (hematology, blood chemistry, and urinalysis), abnormal Physical examinations findings | Day 43 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Standardized Uptake Value (SUV) of [⁶⁸Ga]Ga-DOTA-STR-17126 | Day 2 post-dose | 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. |
| PET/CT image quality of [⁶⁸Ga]Ga-DOTA-STR-17126 | Day 2 post-dose | 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. |
| Tumour to Background Ratio (TBR) of [⁶⁸Ga]Ga-DOTA-STR-17126 | Day 2 post-dose | 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. |
| Concentration of [68Ga]Ga-DOTA-STR-17126 and [177Lu]Lu-DOTA-STR-17126 | Day 1 post-dose, Day 2, Day 4, Day 8 | 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) |
| Percentage of injected activity (%IA) in tumour and non-tumour organs | Day 1 post-dose, Day 2, Day 4, Day 8 | Calculate retention pattern within body and blood pool by the percentage of injected activity (%IA) in tumour and non-tumour organs |
| Calculation of absorbed dose (AD, mGy/MBq) | Day 1 post-dose | 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). |
Countries
Australia
Contacts
CONTACTAmma P Owusu, RN BSc MN
CONTACTDuncan Colyer, RN BN PGDip
PRINCIPAL_INVESTIGATORNat Lenzo, MD
Integrated Hematology Oncology Network (Icon Group)
Outcome results
None listed