Massachusetts General Hospital Massachusetts General Hospital 02114 Boston United StatesRekrutierend» Google-Maps Ansprechpartner: Ashley O Meara E-Mail: ALOMEARA@mgh.harvard.edu» Ansprechpartner anzeigenBAMF Health Research 49503 Grand Rapids United StatesRekrutierend» Google-Maps Ansprechpartner: Judith Collea E-Mail: judith.collea@wcgclinical.com» Ansprechpartner anzeigenNovartis Investigative Site 6423906 Tel Aviv IsraelRekrutierend» Google-Maps
Novartis Investigative Site 6525 GA Nijmegen NetherlandsRekrutierend» Google-MapsNovartis Investigative Site 08907 Hospitalet de LLobregat SpainRekrutierend» Google-MapsNovartis Investigative Site 28034 Madrid SpainRekrutierend» Google-MapsNovartis Investigative Site CH 1211 Geneve 14 SwitzerlandRekrutierend» Google-Maps
1. Incidence and severity of dose limiting toxicities of 177Lu-FF58 (Time Frame - From start of study treatment until 6 weeks after): A dose limiting toxicity (DLT) is defined as any AE or abnormal laboratory value of CTCAE (v5.0) Grade 3 or higher that occurs within the DLT evaluation period (i.e., 6 weeks starting from the first administration of 177Lu-FF58) and that is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications.
2. Incidence and severity of adverse events and serious adverse events of 177Lu-FF58 (Time Frame - From start of study treatment until 180 days after the last dose of study treatment, assessed up to approximately 15 months): The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs) due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
3. Dose modifications for 177Lu-FF58 (Time Frame - From start of study treatment until last dose of study treatment, assessed up to approximately 36 weeks): Dose modifications (dose interruptions and reductions) for 177Lu-FF58 will be assessed and summarized using descriptive statistics. The number of patients with dose modification and the reasons will be summarized by treatment groups.
4. Dose intensity for 177Lu-FF58 (Time Frame - From start of study treatment until last dose of study treatment, assessed up to approximately 36 weeks): Dose intensity for 177Lu-FF58 will be assessed and summarized using descriptive statistics. Dose intensity is computed as the ratio of actual cumulative dose received and actual duration of exposure.
Secondary outcome:
1. Overall response rate (ORR) (Time Frame - From start of study treatment until date of progression, assessed up to approximately 34 months): ORR is defined as the proportion of patients with a BOR of complete response (CR) or partial response (PR) as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients). It will be summarized along with the corresponding 90% exact CI using FAS.
2. Duration of Response (DOR) (Time Frame - From start of study treatment until date of progression, assessed up to approximately 34 months): DOR is the time between the first documented response (CR or PR) and the date of progression as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients), or death due to any cause. Here, death due to any cause is considered as an event to be conservative and align with PFS event definition. DOR may be presented graphically if enough events are available for analysis, using Kaplan Meier plots for all patients who achieved a CR/PR in the study. The median DOR and corresponding 90% CI will be presented. Analysis will include responders with confirmed responses.
3. Disease control rate (DCR) (Time Frame - From start of study treatment until date of progression, assessed up to approximately 34 months): DCR is defined as the proportion of patients with a BOR of CR, PR, or stable disease as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients). It will be summarized along with the corresponding 90% exact CI, using FAS.
4. Progression free survival (PFS) (Time Frame - From start of study treatment until date of progression, assessed up to approximately 34 months): PFS is defined as the time from the date of start of treatment to the date of the first documented progression as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients), or death due to any cause.
5. Area Under the Curve (AUC) from 177Lu-FF58 blood radioactivity data (Time Frame - Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.): 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. AUC from time zero to specified time point (mass x time x volume-1) will be listed and summarized using descriptive statistics.
6. Total body clearance from 177Lu-FF58 blood radioactivity data (Time Frame - Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.): 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 total body clearance of drug from the plasma (volume x time-1) will be listed and summarized using descriptive statistics.
7. Observed maximum plasma concentration (Cmax) from 177Lu-FF58 blood radioactivity data (Time Frame - Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.): 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.
8. Volume of distribution during the terminal phase following intravenous elimination (Vz) from 177Lu-FF58 blood radioactivity data (Time Frame - Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.): 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.
9. Terminal elimination half-life (T^1/2) from 177Lu-FF58 blood radioactivity data (Time Frame - Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.): 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.
10. Urinary excretion of radioactivity expressed as a percentage of injected activity (%IA) (Time Frame - Cycle 1: Pre-infusion,beginning of infusion to first SPECT/CT image acquisition,first SPECT/CT image acquisition and 6 hours(hr) post-end-of infusion(EOI),6-24hr post-EOI,24-48hr post-EOI,48-72hr post-EOI. Cycle= 6 weeks or 3 weeks depending on schedule.): 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.
11. Time-activity curves (TACs) related to 177Lu-FF58 uptake in organs and tumor lesions (Time Frame - Cycle 1 Day 1, Cycle 1 Day 2 (24 hours (hr)), Cycle 1 Day 3 (48 hr), Cycle 1 Day 4 (72 hr), Cycle 1 Day 8 (168 hr). Cycle = 6 weeks or 3 weeks depending on schedule.): Time-activity curves (TACs) for the various organs and tumor lesions will be produced as fraction of injected activity per gram of tissue (%IA/g) as a function of time.
12. Absorbed dose of 177Lu-FF58 (Time Frame - Cycle 1 Day 1, Cycle 1 Day 2 (24 hours (hr)), Cycle 1 Day 3 (48 hr), Cycle 1 Day 4 (72 hr), Cycle 1 Day 8 (168 hr). Cycle = 6 weeks or 3 weeks depending on schedule.): The absorbed dose in target organs will be summarized with descriptive statistics. Lesion number will be assigned by dosimetry expert.
13. Incidence and severity of adverse events and serious adverse events of 68Ga-FF58 (Time Frame - From Imaging visit until 14 days after 68Ga-FF58 administration, or until first dose of study treatment): The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs) due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
14. Imaging properties: Visual and quantitative assessment (expressed as SUV) and tumor-to-background ratio (TBR) of 68Ga-FF58 uptake in organs and tumor lesions over time (Time Frame - From Imaging until 1 hour (hr), 2 hr and 3 hr after 68Ga-FF58 administration): After 68Ga-FF58 administration, 68Ga-FF58 PET/CT or PET/MRI will be performed. The statistical analyses of imaging properties of 68Ga-FF58 will be descriptive in nature and will include summaries and graphical presentations of data. No formal testing will be performed.
