To Evaluate the Optimal Dose of 68Ga-OPS202 as a PET (Positron Emission Tomography) Imaging Agent in Subjects With Gastroenteropancreatic Neuroendocrine Tumour (GEP-NET)

Study Overview
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Brief Summary
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The purpose of this clinical research is to confirm the optimal dose of 68Ga-satoreotide trizoxetan (68Ga-IPN01070), formerly 68Ga-OPS202, as a PET imaging agent to be used to detect and localize gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). 68Ga-IPN01070 is a radiolabelled imaging agent to be used in association with Positron-Emission-Tomography (PET). 68Ga-IPN01070 is made of two main components: 1) IPN01070, an antagonistic somatostatin analogue which binds to the somatostatin receptor (type 2) present on the surface of the tumor cells and 2) Gallium-68, a radioisotope that combined with IPN01070 can be seen in the PET scanner.

Official Title
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A Multicentre, Randomised, Dose-confirmation, Factorial Phase II Study to Evaluate the Optimal Dose of 68Ga-OPS202 as a PET Imaging Agent in Subjects With Gastroenteropancreatic Neuroendocrine Tumour (GEP-NET)

Conditions
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Gastro-Enteropancreatic Neuroendocrine Tumor

Intervention / Treatment
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* Drug: Satoreotide trizoxetan 5-20μg
* Drug: Satoreotide trizoxetan 30-45μg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed, well differentiated functioning or non-functioning metastatic GEP-NET (Grade I and II as per World Health Organisation classification 2010) Confirmed presence of somatostatin receptors (type 2) on technically evaluable tumour lesions documented by a positive Somatostatin Receptor Scan acquired within 6 months prior to screening (Visit 1) and showing minimally two lesions in at least one of the key organs; these images shall be available to be sent to the imaging core lab electronically to ascertain quality and admissibility Body weight between 50 kg (110 lb) and 110 kg (243 lb), inclusive Adequate bone marrow, liver and renal function Eastern Cooperative Oncology Group (ECOG) performance status ≤2 Exclusion Criteria: Fewer than five lesions in total and more than 25 lesions/organ detected by the previous somatostatin receptor scan in key organs: liver, lymph nodes, bone or lungs Subject who have received treatment of any somatostatin analogue, including Somatuline® Autogel® /Depot®, Sandostatin® LAR within 28 days, and Sandostatin® within 24 hours prior to first 68Ga-OPS202 administration Prior or planned administration of a radiopharmaceutical within 8 half-lives of the radionuclide Any condition that precludes the proper performance of PET and/or CT scan: a) Subjects who are not able to tolerate the CT contrast agent, b) Subjects with metal implants or arthroplasty, or any other objects that might interfere with the PET and/or CT analysis, c) Subjects unable to raise arms for prolonged imaging purposes, d) Subjects unable to lie still for the entire imaging time, e) Subjects weighing greater than 110 kg (243 lb)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5-20μg/40-80 MBq, 30-45μg/100-140 MBq<br>Subjects will receive a first intravenous (i.v.) injection of satoreotide trizoxetan with a peptide mass dose range of 5 to 20 μg and a radioactivity dose range 40 to 80 MBq. After 15 to 21 days the subjects will receive a second i.v. injection of satoreotide trizoxetan with a peptide mass dose range of 30-45 μg and a radioactivity dose range 100 to 140 MBq. | Drug: Satoreotide trizoxetan 5-20μg<br>* Positron emission tomography (PET) imaging agent<br>* Other names: 68Ga-OPS202 5-20μg, 68Ga-IPN01070 5-20μg;Drug: Satoreotide trizoxetan 30-45μg<br>* Positron emission tomography (PET) imaging agent<br>* Other names: 68Ga-OPS202 30-45μg, 68Ga-IPN01070 30-45μg;|
| Experimental: 5-20μg/100-140 MBq, 30-45μg/160-200 MBq<br>Subjects will receive a first i.v. injection of satoreotide trizoxetan with a peptide mass dose range of 5 to 20 μg and a radioactivity dose range 100 to 140 MBq. After 15 to 21 days the subjects will receive a second i.v. injection of satoreotide trizoxetan with a peptide mass dose range of 30-45 μg and a radioactivity dose range 160 to 200 MBq. | Drug: Satoreotide trizoxetan 5-20μg<br>* Positron emission tomography (PET) imaging agent<br>* Other names: 68Ga-OPS202 5-20μg, 68Ga-IPN01070 5-20μg;Drug: Satoreotide trizoxetan 30-45μg<br>* Positron emission tomography (PET) imaging agent<br>* Other names: 68Ga-OPS202 30-45μg, 68Ga-IPN01070 30-45μg;|
| Experimental: 5-20μg/160-200 MBq, 30-45μg/40-80 MBq<br>Subjects will receive a first i.v. injection of satoreotide trizoxetan with a peptide mass dose range of 5 to 20 μg and a radioactivity dose range 160 to 200 MBq. After 15 to 21 days the subjects will receive a second i.v. injection of satoreotide trizoxetan with a peptide mass dose range of 30-45 μg and a radioactivity dose range 40 to 80 MBq. | Drug: Satoreotide trizoxetan 5-20μg<br>* Positron emission tomography (PET) imaging agent<br>* Other names: 68Ga-OPS202 5-20μg, 68Ga-IPN01070 5-20μg;Drug: Satoreotide trizoxetan 30-45μg<br>* Positron emission tomography (PET) imaging agent<br>* Other names: 68Ga-OPS202 30-45μg, 68Ga-IPN01070 30-45μg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Lesion Counts Presented by Combination of Injected Peptide/Radioactivity Dose Ranges | For each combination of injected peptide/radioactivity dose range, relative lesion counts were measured as the ratio of the number of lesions detected by 68Ga-satoreotide trizoxetan PET/CT and PET readings to the number of lesions assessed by standard-of-truth (SoT). The SoT in this study was the contrast enhanced (ce)CT scan images acquired at Visit 2 (Day 1) and Visit 3 (Days 16 to 22). Relative lesion counts for PET/CT and PET readings are presented for all organs, primary site of GEP-NET and per organ by each combination of injected peptide/radioactivity dose range after the 1st and 2nd injections. | Day 1 and Days 16 to 22 | 
| Relative Lesion Counts Presented by Peptide Mass and Radioactivity Dose Ranges | For each combination of injected peptide/radioactivity dose range, relative lesion counts were measured as the ratio of the number of lesions detected by 68Ga-satoreotide trizoxetan PET/CT and PET readings to the number of lesions assessed by SoT. The SoT in this study was the ceCT scan images acquired at Visit 2 (Day 1) and Visit 3 (Day 16 to 22). Relative lesion counts for PET/CT and PET readings are presented for all organs, primary site of GEP-NET and per organ by both peptide mass range and radioactivity dose range. | Day 1 and Days 16 to 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Image Quality as Assessed by Tumour-To-Background Ratio Presented by Combination of Injected Peptide/Radioactivity Dose Range | For each PET assessment, image quality was quantitatively measured by the tumour-to-background ratio, obtained using the mean of all lesions tumour-to-backgrounds, for each of the following organs; liver, lymph nodes, bone and lungs. The tumour-to-background ratio was computed by mean standardised uptake value (SUVmean) of the lesion divided by the SUVmean of the subject's reference tissue (tumour-free liver or aortic blood). A high tumour-to-background ratio indicates high effectiveness of 68Ga-satoreotide trizoxetan as a diagnostic agent. Tumour-to-background ratios are presented for primary site of GEP-NET and per organ by each combination of injected peptide/radioactivity dose range. | Day 1 and Days 16 to 22 | 
| Image Quality as Assessed by Tumour-To-Background Ratio Presented by Peptide Mass and Radioactivity Dose Ranges | For each PET assessment image quality was quantitatively measured by the tumour-to-background ratio, obtained using the mean of all lesions tumour-to-backgrounds, for each of the following organs; liver, lymph nodes, bone and lungs. The tumour-to-background ratio was computed by SUVmean of the lesion divided by the SUVmean of the subject's reference tissue (tumour-free liver or aortic blood). A high tumour-to-background ratio indicates high effectiveness of 68Ga-satoreotide trizoxetan as a diagnostic agent. Tumour-to-background ratios are presented for primary site of GEP-NET and per organ by both peptide mass range and radioactivity dose range. | Day 1 and Days 16 to 22 | 
| Image Quality as Assessed by Independent Blinded Readers Quality Score | A qualitative analysis of the image was assessed by 2 independent blinded readers using a quality score (performed as a back-up to the quantitative quality measured by tumour-to-background analysis). For each PET/CT and PET assessment, each reader performed a direct comparison of the 2 scans from Visit 2 and Visit 3. They noted which scan provided superior images based on overall image quality and lesion count and attributed a score for each assessment. The score for the assessment having superior images was set to 1, and score for the assessment not selected was set to 0. In case of equal quality, both assessments had a score of 1. The image quality score for PET/CT and PET readings as cumulative sum of readers' scores across all subjects by peptide mass and radioactivity dose range combination is presented. Score ranges from 0-16 with higher score indicating more assessments classed as superior. | Day 1 and Days 16 to 22 | 
| Lesion Maximum Standardised Uptake Value (SUVmax) Presented by Combination of Injected Peptide/Radioactivity Dose Ranges | For each PET assessment, SUVmax was measured for each lesion, up to a maximum of 5 most avid lesions per organ that were confirmed by SoT assessment. In order to obtain a unique measure per organ, values of the SUVmax were computed within each of the following organs; liver, lymph nodes, bone and lungs. SUVmax results are presented for primary site of GEP-NET and per organ by each combination of injected peptide/radioactivity dose range. | Day 1 and Days 16 to 22 | 
| Lesion SUVmax Presented by Peptide Mass and Radioactivity Dose Ranges | For each PET assessment, SUVmax was measured for each lesion, up to a maximum of 5 most avid lesions per organ that are confirmed by SoT assessment. In order to obtain a unique measure per organ, mean of the SUVmax was computed within each of the liver, lymph nodes, bone and lungs. SUVmax results are presented for primary site of GEP-NET and per organ by both peptide mass range and radioactivity dose range. | Day 1 and Days 16 to 22 | 
| Absolute Number of Lesions Detected by 68Ga-Satoreotide Trizoxetan Presented by Combination of Injected Peptide/Radioactivity Dose Range | For each PET/CT and PET assessment, the absolute number of lesions detected by 68Ga-satoreotide trizoxetan were reported for each of the following anatomic sites; primary site of GEP-NET, liver, lymph nodes, axial/appendicular skeleton (bone) and lungs. The absolute number of lesions for PET/CT and PET readings for the 5 anatomic sites are presented by each combination of injected peptide/radioactivity dose range. | Day 1 and Days 16 to 22 | 
| Absolute Number of Lesions Detected by 68Ga-Satoreotide Trizoxetan Presented by Peptide Mass and Radioactivity Dose Ranges | For each PET/CT and PET assessment, the absolute number of lesions detected by 68Ga-satoreotide trizoxetan were reported for each of the following anatomic sites; primary site of GEP-NET, lymph nodes, liver, axial/appendicular skeleton (bone) and lungs. The absolute number of lesions for PET/CT and PET readings for the 5 anatomic sites are presented by both peptide mass range and radioactivity dose range. | Day 1 and Days 16 to 22 | 
| Difference in Number of Lesions Detected by 68Ga-Satoreotide Trizoxetan Compared to Lesions Detected by SoT Presented by Combination of Injected Peptide/Radioactivity Dose Range | For each PET/CT and PET assessment, the number of lesions detected by 68Ga-satoreotide trizoxetan and SoT (ceCT) were reported for each of the following anatomic sites; primary site of GEP-NET, lymph nodes, liver, axial/appendicular skeleton (bone) and lungs. The difference was calculated by number of lesions detected by 68Ga-satoreotide trizoxetan - number of lesions detected by ceCT scan. A positive difference indicates that more lesions were detected by 68Ga-satoreotide trizoxetan than by ceCT scan. A negative difference indicates that more lesions were detected by ceCT scan than by 68Ga-satoreotide trizoxetan. The difference in number of lesions for PET/CT and PET readings for the 5 anatomic sites are presented by each combination of injected peptide/radioactivity dose range. | Day 1 and Days 16 to 22 | 
| Difference in Number of Lesions Detected by 68Ga-Satoreotide Trizoxetan Compared to Lesions Detected by SoT Presented by Peptide Mass and Radioactivity Dose Ranges | For each PET/CT and PET assessment, the number of lesions detected by 68Ga-satoreotide trizoxetan and SoT (ceCT) were reported for each of the following anatomic sites; primary site of GEP-NET, lymph nodes, liver, axial/appendicular skeleton (bone) and lungs. The difference was calculated by number of lesions detected by 68Ga-satoreotide trizoxetan - number of lesions detected by ceCT scan. A positive difference indicates that more lesions were detected by 68Ga-satoreotide trizoxetan than by ceCT scan. A negative difference indicates that more lesions were detected by ceCT scan than by 68Ga-satoreotide trizoxetan. The difference in number of lesions for PET/CT and PET readings for the 5 anatomic sites results are presented by both peptide mass range and radioactivity dose range. | Day 1 and Days 16 to 22 |