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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-004038-39 | EudraCT Number |
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This is a First-In-Human (FIH) study of [68Ga]-FF58 to characterize the imaging properties, safety, biodistribution and dosimetry properties of [68Ga]-FF58 in adults with relapsed or refractory (r/r) glioblastoma multiforme (GBM), breast cancer (BC) that has metastasized to the brain, gastroesophageal adenocarcinoma (GEA) or pancreatic ductal adenocarcinoma (PDAC) expected to overexpress alpha-v beta 3 (αvβ3) and alpha-v beta 5 (αvβ5) integrins.
Approximately 80 patients were planned to be enrolled into the study, 20 patients with GBM, 20 patients with BC that had metastasized to the brain, 20 with GEA and 20 with PDAC.
The study included an imaging characterization part and an expansion part. In the imaging characterization part, approximately 24 patients were planned to be enrolled, 6 with r/r GBM, 6 with BC that had metastasized to the brain, 6 with GEA and 6 with PDAC. Due to the early termination of the study, the expansion part was not started.
Both parts of the study (imaging characterization and expansion) included a dosimetry sub-group in which the distribution, pharmacokinetics (PK), radiation dosimetry and absorbed doses in tissue and tumor were to be assessed. However, no patients were enrolled in the dosimetry sub-group.
All patients enrolled in the study received a single dose of [68Ga]-FF58 and underwent [68Ga]-FF58 positron emission tomography (PET) imaging at different timepoints on Day 1 as well as conventional imaging (high resolution computed tomography (CT) or magnetic resonance imaging (MRI)).
The estimated study duration for each individual patient was approximately 44 days (including screening period of 28 days and 14 days of follow-up (FU)).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Glioblastoma Multiforme | Experimental | All eligible participants will receive recommended dose of [68Ga]-FF58 of 3 Megabecquerel (MBq)/Kg (+/- 10%) [but not more than 250 and not less than 150 MBq]. |
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| Brain Metastasis from Breast Cancer | Experimental | All eligible participants will receive recommended dose of [68Ga]-FF58 of 3 Megabecquerel (MBq)/Kg (+/- 10%) [but not more than 250 and not less than 150 MBq]. |
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| Gastroesophageal adenocarcinoma | Experimental | All eligible participants will receive recommended dose of [68Ga]FF58 of 3 Megabecquerel (MBq)/Kg (+/-10%) [but not more than 250 and not less than 150 MBq] |
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| Pancreatic ductal adenocarcinoma | Experimental | All eligible participants will receive recommended dose of [68Ga]FF58 of 3 Megabecquerel (MBq)/Kg (+/-10%) [but not more than 250 and not less than 150 MBq] |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 68Ga-FF58 | Drug | Single intravenous radiolabeled gallium FF58 injection determined by body weight (3 Megabecquerel (MBq)/Kg (+/- 10%)). Administered dose must not be lower than 150 MBq or higher than 250 MBq. |
| Measure | Description | Time Frame |
|---|---|---|
| Time-activity curves (TACs) from 68Ga-FF58 PET/CT images | Time activity curves (TACs) for the various organs will be produced as mean Standard Uptake Values (SUV) of the lesions over time. | [68Ga]-FF58 PET imaging acquired at Day 1 |
| Standard Uptake Value (SUV) mean and max in lesions detected by PET scans | Targeting properties of 68GaFF58 will be evaluated by semi quantitatively assessing radiotracer uptake at lesion level, identified via PET/CT imaging (4 scans). The SUVmean and SUVmax of each lesion will be calculated and reported by lesion location with summary statistics. | [68Ga]-FF58 PET imaging acquired at Day 1 |
| Tumor to Background Ratio (TBR) of lesions detected by PET scans | Targeting properties of 68Ga-FF58 will be evaluated by semi quantitatively assessing radiotracer uptake at lesion level, identified via PET/CT imaging (4 scans). The lesion Tumor to Background Ratio (TBR) will be defined as the ratio of the lesion SUV over the reference region SUV. TBRs will be calculated for both SUVmax(lesion) / SUVmean and reported by lesion location with summary statistics. Different regions will be used as reference, in order to satisfy the most appropriate one for each type of lesion. | [68Ga]-FF58 PET imaging acquired at Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Treatment Emergent Adverse Events | Treatment-emergent adverse events (TEAEs) will be collected from first dosing (single administration, Day 1) up to last follow-up visit or the patient withdrew consent. The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Lyon | 69373 | France | |||
| Novartis Investigative Site |
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| Label | URL |
|---|---|
| Study Results | View source |
| A Plain Language Trial Summary is available on www.novctrd.com | View source |
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Imaging study
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| From first dosing (single administration, Day 1) up to 14 days post infusion |
| Percentage of lesions detected by conventional scans, PET scans, or both modalities | The percentage of lesions detected by conventional imaging (high resolution CT or MRI acquired jointly or within 24 hours before or after the [68Ga]-FF58 PET scan), [68Ga]-FF58 PET scans , or both modalities will be summarized descriptively for all patients and split by indication. | [68Ga]-FF58 PET imaging acquired at Day 1 |
| Lesion-level analyses of diagnostics by [68Ga]-FF58 compared with conventional imaging | At lesion level, overall, positive, and negative agreement of [68Ga]-FF58 will be calculated based on the aforementioned tabulations as follows: • Overall agreement = 100% x (Double positive + Double negative) / total number of lesions identified by either imaging procedures
| [68Ga]-FF58 PET imaging acquired at Day 1 |
| Dosimetry Group: Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of 68Ga-FF58 | Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity-based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. AUClast will be listed and summarized using descriptive statistics. | Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion) |
| Dosimetry Group: Time of maximum observed drug concentration occurrence (Tmax) of 68Ga-FF58 | Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Tmax will be listed and summarized using descriptive statistics. | Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion) |
| Dosimetry Group: Observed maximum plasma concentration (Cmax) of 68Ga-FF58 | Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Cmax will be listed and summarized using descriptive statistics. | Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion) |
| Dosimetry Group: Terminal elimination half-life (T^1/2) of 68Ga-FF58 | Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. The half-life will be listed and summarized using descriptive statistics. | Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion) |
| Dosimetry Group: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of 68Ga-FF58 | Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. AUCinf will be listed and summarized using descriptive statistics. | Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion) |
| Dosimetry Group: Total systemic clearance for intravenous administration (CL) of 68Ga-FF58 | Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. CL will be listed and summarized using descriptive statistics. | Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion) |
| Dosimetry Group: Volume of distribution during the terminal phase following intravenous elimination (Vz) of 68Ga-FF58 | Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Vz will be listed and summarized using descriptive statistics. | Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion) |
| Dosimetry Group: Urinary excretion of radioactivity expressed as a percentage of injected activity (%IA) | Urine samples will be collected over specified time intervals and analysed for radioactivity. The radioactivity excreted in each interval as a percentage of injected activity (%IA) will be listed and summarized using descriptive statistics. | Day 1 (0-30, 30-120, 120-180, 180-300 minutes post infusion) |
| Dosimetry Group: Absorbed dose of 68Ga- FF58 | The absorbed dose in target organs will be summarized with descriptive statistics. Lesion number will be assigned by dosimetry expert. | [68Ga]-FF58 PET imaging acquired at Day 1 |
| Dosimetry Group: Effective whole-body dose of 68Ga- FF58 | The effective radiation dose will be summarized with descriptive statistics. Lesion number will be assigned by dosimetry expert. | [68Ga]-FF58 PET imaging acquired at Day 1 |
| Essen |
| 45147 |
| Germany |
| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| D001932 | Brain Neoplasms |
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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