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Study of [68Ga]-FF58 in Patients With Selected Solid Tumors Expected to Overexpress αvβ3 and αvβ5 Integrins.

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ClinicalTrials.gov Identifier: NCT04712721
Recruitment Status : Not yet recruiting
First Posted : January 15, 2021
Last Update Posted : January 19, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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) or Human Epidermal growth factor Receptor 2 positive (Her2+) breast cancer that has metastasized to the brain expected to overexpress alpha-v beta 3 (αvβ3) and alpha-v beta 5 (αvβ5) integrins.

Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme Brain Neoplasms Drug: 68Ga-FF58 Early Phase 1

Detailed Description:

Approximately 40 patients (male and female) will be enrolled into the study, 20 patients with GBM and 20 patients with Her2+ BC that has metastasized to the brain.

The study will have an imaging characterization part and an expansion part. In the imaging characterization part of the study, approximately 12 patients will be enrolled, 6 with r/r GBM and 6 with Her2+ BC that has metastasized to the brain.

Both parts of the study (imaging characterization and expansion) will include a dosimetry sub-group in which the distribution, pharmacokinetics (PK), radiation dosimetry and absorbed doses in tissue and tumor will be assessed.

All patients enrolled in the study will receive a single dose of [68Ga]-FF58 and undergo [68Ga]-FF58 PET imaging at different timepoints on Day 1 as well as conventional imaging (high resolution CT or MRI).

The estimated study duration for each individual patient is approximately 44 days (including screening period of 28 days and 14 days of follow-up (FU)).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Imaging study
Masking: None (Open Label)
Primary Purpose: Other
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 Expectedto Overexpress αvβ3 and αvβ5 Integrins.
Estimated Study Start Date : March 24, 2021
Estimated Primary Completion Date : May 9, 2022
Estimated Study Completion Date : May 9, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Glioblastoma Multiforme
All eligible participants will receive recommended dose of [68Ga]-FF58 of 3 Mega Becquerel (MBq)/Kg (+/- 10%) [but not more than 250 and not less than 150 MBq].
Drug: 68Ga-FF58
single intravenous radio-labelled FF58 Gallium ligand injection determined by body weight (3 Mega Becquerel (MBq)/Kg (+/- 10%)). Administered dose must not be lower than 150 MBq or higher than 250 MBq.

Experimental: Brain Metastasis from HER2+ Breast Cancer
All eligible participants will receive recommended dose of [68Ga]-FF58 of 3 Mega Becquerel (MBq)/Kg (+/- 10%) [but not more than 250 and not less than 150 MBq].
Drug: 68Ga-FF58
single intravenous radio-labelled FF58 Gallium ligand injection determined by body weight (3 Mega Becquerel (MBq)/Kg (+/- 10%)). Administered dose must not be lower than 150 MBq or higher than 250 MBq.




Primary Outcome Measures :
  1. Non-decay corrected tissue time-activity curves (TACs) from 68Ga-FF58 PET/CT images [ Time Frame: 68Ga-FF58 PET imaging acquired at Day 1 ]
    Time activity curves (TACs) for the various organs will be produced as non decay-corrected fraction of injected activity (%IA) per organ.

  2. Number of lesions detected by [68Ga]-FF58 [ Time Frame: [68Ga]-FF58 PET imaging acquired at Day 1 ]
    The preliminary targeting properties of [68Ga]-FF58 will be assessed by summarizing the number of lesions identified by Positron Emission Tomography (PET), as well as by tumor type.

  3. Number of Participants with Lesions detected by [68Ga]-FF58 per Location [ Time Frame: [68Ga]-FF58 PET imaging acquired at Day 1 ]
    The preliminary targeting properties of [68Ga]-FF58 will be assessed by summarizing the location of lesions identified by PET, as well as by tumor type.

  4. Standard Uptake Value (SUV) mean and max in lesions detected by PET scans [ Time Frame: [68Ga]-FF58 PET imaging acquired at Day 1 ]
    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.

  5. Tumor to Background Ratio (TBR) of lesions detected by PET scans [ Time Frame: 68Ga-FF58 PET imaging acquired at Day 1 ]
    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.


Secondary Outcome Measures :
  1. Number of Participants with Treatment Emergent Adverse Events [ Time Frame: From first dosing (single administration, Day 1) up to 14 days post infusion ]
    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.

  2. Percentage of lesions detected by conventional scans, PET scans, or both modalities [ Time Frame: 68Ga-FF58 PET imaging acquired at Day 1 ]
    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.

  3. Lesion-level analyses of diagnostics by [68Ga]-FF58 compared with conventional imaging [ Time Frame: 68Ga-FF58 PET imaging acquired at Day 1 ]

    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

    • Positive agreement = 100% x Double positive / (Double positive + Comparator single positive)
    • Negative agreement = 100% x Double negative / (Double negative + Comparator single negative).

  4. Dosimetry Group: Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of 68Ga-FF58 [ Time Frame: Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion) ]
    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 activitiy 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.

  5. Dosimetry Group: Time of maximum observed drug concentration occurrence (Tmax) of 68Ga-FF58 [ Time Frame: Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion) ]
    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.

  6. Dosimetry Group: Observed maximum plasma concentration (Cmax) of 68Ga-FF58 [ Time Frame: Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion) ]
    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.

  7. Dosimetry Group: Terminal elimination half-life (T^1/2) of 68Ga-FF58 [ Time Frame: Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion) ]
    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.

  8. Dosimetry Group: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of 68Ga-FF58 [ Time Frame: Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion) ]
    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.

  9. Dosimetry Group: Total systemic clearance for intravenous administration (CL) of 68Ga-FF58 [ Time Frame: Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion) ]
    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.

  10. Dosimetry Group: Volume of distribution during the terminal phase following intravenous elimination (Vz) of 68Ga-FF58 [ Time Frame: Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion) ]
    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.

  11. Dosimetry Group: Urinary excretion of radioactivity expressed as a percentage of injected activity (%IA) [ Time Frame: Day 1 (0-30, 30-120, 120-180, 180-300 minutes post infusion) ]
    Urine samples will be collected over specified time intervals and analysed for radioactivitiy. The radioactivity excreted in each interval as a percentage of injected activity (%IA) will be listed and summarized using descriptive statistics.

  12. Dosimetry Group: Absorbed dose of 68Ga- FF58 [ Time Frame: 68Ga-FF58 PET imaging acquired at Day 1 ]
    The absorbed dose in target organs will be summarized with descriptive statistics. Lesion number will be assigned by dosimetry expert.

  13. Dosimetry Group: Effective whole-body dose of 68Ga- FF58 [ Time Frame: 68Ga-FF58 PET imaging acquired at Day 1 ]
    The effective radiation dose will be summarized with descriptive statistics. Lesion number will be assigned by dosimetry expert.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 Her2+ 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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04712721


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com

Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04712721    
Other Study ID Numbers: CAAA504A12101
2020-004038-39 ( EudraCT Number )
First Posted: January 15, 2021    Key Record Dates
Last Update Posted: January 19, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Glioblastoma Multiforme
GBM
Human Epidermal growth factor Receptor 2 positive
Her2+
Breast Cancer
BC
Brain Metastasis from Her2+ BC
alpha-v beta 3 integrin
αvβ3
alpha-v beta 5 integrin
αvβ5
Overexpression
Dosimetry
68Gallium
68Ga
FF58
[68Ga]-FF58
Additional relevant MeSH terms:
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Glioblastoma
Brain Neoplasms
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases