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

Primary Purpose

Glioblastoma Multiforme, Brain Neoplasms, Gastroesophageal Adenocarcinoma

Status

Recruiting

Phase

Early Phase 1

Locations

International

Study Type

Interventional

Intervention

68Ga-FF58

About this trial

This is an interventional other trial for Glioblastoma Multiforme focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

City of Hope National Medical Center Dept.ofCityofHopeMedicalCtr(1)Recruiting
Uni of TX MD Anderson Cancer CntrRecruiting
Novartis Investigative SiteRecruiting
Novartis Investigative SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Glioblastoma Multiforme

Brain Metastasis from Breast Cancer

Gastroesophageal adenocarcinoma

Pancreatic ductal adenocarcinoma

Arm Description

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].

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]

Outcomes

Primary Outcome Measures

Non-decay corrected tissue time-activity curves (TACs) from 68Ga-FF58 PET/CT images

Time activity curves (TACs) for the various organs will be produced as non decay-corrected fraction of injected activity (%IA) per organ.

Number of lesions detected by [68Ga]-FF58

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.

Number of Participants with Lesions detected by [68Ga]-FF58 per Location

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.

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.

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.

Secondary Outcome Measures

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT04712721

First Posted

December 11, 2020

Last Updated

October 17, 2023

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT04712721

Brief Title

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

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 14, 2021 (Actual)

Primary Completion Date

February 15, 2024 (Anticipated)

Study Completion Date

February 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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 will be enrolled into the study, 20 patients with GBM, 20 patients with BC that has metastasized to the brain, 20 with GEA and 20 with PDAC. The study will have an imaging characterization part and an expansion part. In the imaging characterization part, approximately 24 patients will be enrolled, 6 with r/r GBM, 6 with BC that has metastasized to the brain, 6 with GEA and 6 with PDAC. 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)).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Other

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Model Description

Imaging study

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Glioblastoma Multiforme

Arm Type

Experimental

Arm Description

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].

Arm Title

Brain Metastasis from Breast Cancer

Arm Type

Experimental

Arm Description

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].

Arm Title

Gastroesophageal adenocarcinoma

Arm Type

Experimental

Arm Description

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]

Arm Title

Pancreatic ductal adenocarcinoma

Arm Type

Experimental

Arm Description

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]

Intervention Type

Drug

Intervention Name(s)

68Ga-FF58

Intervention Description

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.

Primary Outcome Measure Information:

Title

Non-decay corrected tissue time-activity curves (TACs) from 68Ga-FF58 PET/CT images

Description

Time activity curves (TACs) for the various organs will be produced as non decay-corrected fraction of injected activity (%IA) per organ.

Time Frame

[68Ga]-FF58 PET imaging acquired at Day 1

Title

Number of lesions detected by [68Ga]-FF58

Description

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.

Time Frame

[68Ga]-FF58 PET imaging acquired at Day 1

Title

Number of Participants with Lesions detected by [68Ga]-FF58 per Location

Description

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.

Time Frame

[68Ga]-FF58 PET imaging acquired at Day 1

Title

Standard Uptake Value (SUV) mean and max in lesions detected by PET scans

Description

Time Frame

[68Ga]-FF58 PET imaging acquired at Day 1

Title

Tumor to Background Ratio (TBR) of lesions detected by PET scans

Description

Time Frame

[68Ga]-FF58 PET imaging acquired at Day 1

Secondary Outcome Measure Information:

Title

Number of Participants with Treatment Emergent Adverse Events

Description

Time Frame

From first dosing (single administration, Day 1) up to 14 days post infusion

Title

Percentage of lesions detected by conventional scans, PET scans, or both modalities

Description

Time Frame

[68Ga]-FF58 PET imaging acquired at Day 1

Title

Lesion-level analyses of diagnostics by [68Ga]-FF58 compared with conventional imaging

Description

Time Frame

[68Ga]-FF58 PET imaging acquired at Day 1

Title

Dosimetry Group: Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of 68Ga-FF58

Description

Time Frame

Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion)

Title

Dosimetry Group: Time of maximum observed drug concentration occurrence (Tmax) of 68Ga-FF58

Description

Time Frame

Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion)

Title

Dosimetry Group: Observed maximum plasma concentration (Cmax) of 68Ga-FF58

Description

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.

Time Frame

Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion)

Title

Dosimetry Group: Terminal elimination half-life (T^1/2) of 68Ga-FF58

Description

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.

Time Frame

Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion)

Title

Dosimetry Group: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of 68Ga-FF58

Description

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.

Time Frame

Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion)

Title

Dosimetry Group: Total systemic clearance for intravenous administration (CL) of 68Ga-FF58

Description

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.

Time Frame

Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion)

Title

Dosimetry Group: Volume of distribution during the terminal phase following intravenous elimination (Vz) of 68Ga-FF58

Description

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.

Time Frame

Day 1 (0, 0-5, 10, 30, 60, 120, 180-240, 300 minutes post infusion)

Title

Dosimetry Group: Urinary excretion of radioactivity expressed as a percentage of injected activity (%IA)

Description

Time Frame

Day 1 (0-30, 30-120, 120-180, 180-300 minutes post infusion)

Title

Dosimetry Group: Absorbed dose of 68Ga- FF58

Description

The absorbed dose in target organs will be summarized with descriptive statistics. Lesion number will be assigned by dosimetry expert.

Time Frame

[68Ga]-FF58 PET imaging acquired at Day 1

Title

Dosimetry Group: Effective whole-body dose of 68Ga- FF58

Description

The effective radiation dose will be summarized with descriptive statistics. Lesion number will be assigned by dosimetry expert.

Time Frame

[68Ga]-FF58 PET imaging acquired at Day 1

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Novartis Pharmaceuticals

Phone

1-888-669-6682

novartis.email@novartis.com

First Name & Middle Initial & Last Name or Official Title & Degree

Novartis Pharmaceuticals

Phone

+41613241111

novartis.email@novartis.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

City of Hope National Medical Center Dept.ofCityofHopeMedicalCtr(1)

City

Duarte

State/Province

California

ZIP/Postal Code

91010 3000

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Miranda Lee

mirlee@coh.org

First Name & Middle Initial & Last Name & Degree

Stephanie Yoon

Facility Name

Uni of TX MD Anderson Cancer Cntr

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jacqueline Kan

Phone

+1 713 792 2921

JWKan1@mdanderson.org

First Name & Middle Initial & Last Name & Degree

Jordi Rodon Ahnert

Facility Name

Novartis Investigative Site

City

Lyon

ZIP/Postal Code

69373

Country

France

Individual Site Status

Recruiting

Facility Name

Novartis Investigative Site

City

Essen

ZIP/Postal Code

45147

Country

Germany

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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