Clinical trial NCT04712721: Study of [68Ga]-FF58 in Patients With Selected Solid Tumors Expected to Overexpress αvβ3 and αvβ5 Integrins.
Official title: Phase I, Open-label, Multicenter Study to Evaluate the Imaging Performance, Safety, Biodistribution and Dosimetry of [68Ga]-FF58 in Adult Patients With Selected Solid Tumors Expected to Overexpress αvβ3 and αvβ5 Integrins.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Glioblastoma Multiforme
Brain Neoplasms
Gastroesophageal Adenocarcinoma
Pancreatic Ductal Adenocarcinoma
Keywords: Glioblastoma Multiforme
GBM
Breast Cancer
BC
Brain Metastasis from BC
Gastroesophageal adenocarcinoma
GEA
Pancreatic ductal adenocarcinoma
PDAC
alpha-v beta 3 integrin
αvβ3
alpha-v beta 5 integrin
αvβ5
Dosimetry
68Gallium
68Ga
FF58
[68Ga]-FF58
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-01-15
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Imaging study
Primary purpose: OTHER

Brief summary: 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.

Detailed description: 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)).

Eligibility criteria: Inclusion Criteria:

* Signed informed consent must be obtained prior to participation in the study
* Patients with histologically or cytologically confirmed and documented r/r GBM that has progressed after prior radiation therapy and have not received prior bevacizumab OR patients with BC that has metastasized to the brain and who should have at least one newly diagnosed brain metastasis that has not been resected or irradiated, or has been irradiated and progressed OR patients with histologically or cytologically confirmed and documented locally advanced or metastatic GEA (i.e., adenocarcinoma of the stomach (intestinal subtype), esophagus, or gastroesophageal junction), either untreated or r/r after one or more lines of treatment OR patients with histologically or cytologically confirmed and documented locally advanced or metastatic PDAC, either untreated or r/r after one or more lines of treatment.

Exclusion Criteria:

* Creatinine clearance (calculated using Cockcroft-Gault formula) \<40 mL/min.
* Unmanageable bladder outflow obstruction or urinary incontinence.
* QTcF \> 480 msec on screening ECG or congenital long QT syndrome.
* Any condition that requires chronic treatment with anticoagulants or antiplatelet agents
* Patients with a known bleeding disorder
* Administration of a radiopharmaceutical within a period corresponding to 10 half-lives of the radionuclide used prior to injection of \[68Ga\]-FF58.
* Pregnant women. Women who are breastfeeding must express and discard breast milk for 12 hours after \[68Ga\]-FF58 administration and must also stop breast feeding during this same period. Males and females must abstain from sexual intercourse for 12 hours after \[68Ga\]-FF58 administration.
* Total bilirubin \> 1.5 x ULN (except for patients with Gilbert's syndrome who are excluded if total bilirubin \> 3.0 x ULN) or direct bilirubin \> 1.5 x ULN
* Alanine aminotransferase (ALT) \> 3 x ULN, except for patients that have tumor involvement of the liver, who are excluded if ALT \> 5 x ULN
* Aspartate aminotransferase (AST) \> 3 x ULN, except for patients that have tumor involvement of the liver, who are excluded if AST \> 5 x ULN

Primary outcomes:
measure: Time-activity curves (TACs) from 68Ga-FF58 PET/CT images
timeFrame: [68Ga]-FF58 PET imaging acquired at Day 1
measure: Standard Uptake Value (SUV) mean and max in lesions detected by PET scans
timeFrame: [68Ga]-FF58 PET imaging acquired at Day 1
measure: Tumor to Background Ratio (TBR) of lesions detected by PET scans
timeFrame: [68Ga]-FF58 PET imaging acquired at Day 1
Secondary outcomes:
measure: Number of Participants with Treatment Emergent Adverse Events
timeFrame: From first dosing (single administration, Day 1) up to 14 days post infusion
measure: Percentage of lesions detected by conventional scans, PET scans, or both modalities
timeFrame: [68Ga]-FF58 PET imaging acquired at Day 1
measure: Lesion-level analyses of diagnostics by [68Ga]-FF58 compared with conventional imaging
timeFrame: [68Ga]-FF58 PET imaging acquired at Day 1
measure: Dosimetry Group: Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of 68Ga-FF58
timeFrame: Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion)
measure: Dosimetry Group: Time of maximum observed drug concentration occurrence (Tmax) of 68Ga-FF58
timeFrame: Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion)
measure: Dosimetry Group: Observed maximum plasma concentration (Cmax) of 68Ga-FF58
timeFrame: Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion)
measure: Dosimetry Group: Terminal elimination half-life (T^1/2) of 68Ga-FF58
timeFrame: Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion)
measure: Dosimetry Group: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of 68Ga-FF58
timeFrame: Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion)
measure: Dosimetry Group: Total systemic clearance for intravenous administration (CL) of 68Ga-FF58
timeFrame: Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion)
measure: Dosimetry Group: Volume of distribution during the terminal phase following intravenous elimination (Vz) of 68Ga-FF58
timeFrame: Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion)
measure: Dosimetry Group: Urinary excretion of radioactivity expressed as a percentage of injected activity (%IA)
timeFrame: Day 1 (0-30, 30-120, 120-180, 180-300 minutes post infusion)
measure: Dosimetry Group: Absorbed dose of 68Ga- FF58
timeFrame: [68Ga]-FF58 PET imaging acquired at Day 1
measure: Dosimetry Group: Effective whole-body dose of 68Ga- FF58
timeFrame: [68Ga]-FF58 PET imaging acquired at Day 1
Other outcomes:
Locations:
city: Lyon
country: France
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: