A Prospective, Open-label Study of [68Ga]Ga-DOTA-TATE in Patients With Neuroendocrine Neoplasms (NENs) and Healthy Volunteers in Japan

Neuroendocrine Neoplasms Clinical Trial

Official title:

A Prospective, Open-label, Multi-center, Single Arm, Phase III Study of [68Ga]Ga-DOTA-TATE in the Diagnosis of Patients With Neuroendocrine Neoplasms (NENs) and Healthy Volunteers in Japan

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06240741
• Other study ID #: CAAA501A11301
• Status: Recruiting
• Phase: Phase 3
• Start date: March 21, 2024
• Est. completion date: July 3, 2025

Study information

• Verified date: May 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: +81337978748
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the diagnostic performance of [68Ga]Ga-DOTA-TATE Positron Emission Tomography (PET)/Computerized Tomography (CT) imaging compared with conventional imaging (CIM) as standard of truth in patients with neuroendocrine neoplasms (NENs) and healthy volunteers (HVs). The data from this study will provide the evidence for diagnosis of [68Ga]Ga-DOTA-TATE PET/CT imaging in patient with NENs in Japan.

Description:

All enrolled participants will undergo [68Ga]Ga-DOTA-TATE PET/CT imaging. [68Ga]Ga-DOTA-TATE will be administered intravenously at a dose of 2 Mega-Becquerel (MBq) / kilogram (kg) (0.054 Millicurie (mCi)/kilogram (kg)) of body weight up to a maximum total dose of 200 MBq (5.4 mCi), and PET/CT imaging will be acquired 40 to 90 minutes after the intravenous administration of [68Ga]Ga-DOTA-TATE.

• Duration of screening period is up to 35 days

• Imaging period will be completed within one day followed by safety follow up visit (Day 8) after imaging day (Day 1)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: July 3, 2025
• Est. primary completion date: July 3, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the study

2. Participants must be adults >= 18 years of age

3. ECOG performance status 0-2

4. For patient with NENs only: Participants with confirmed NENs based on histopathology, imaging and other relevant examination, or with suspected NENs which localization cannot be confirmed by CIM

5. For HVs only: Male or female participant in good health condition as determined by no clinically significant findings from medical history, physical examination, vital signs, lab test and ECG

6. Women of childbearing potential must have a negative urine or blood pregnancy test.

Key Exclusion Criteria:

1. Inability to complete the needed investigational and conventional imaging due to any reason (severe claustrophobia, inability to lie still for the entire imaging time, etc.)

2. Any additional medical condition, serious intercurrent illness, concomitant cancer or other extenuating circumstance that, in the opinion of the Investigator, would indicate a significant risk to safety or impair study participation

3. Known allergy, hypersensitivity, or intolerance to [68Ga]Ga-DOTA-TATE and [111In]In-Pentetreotide

4. Therapeutic use of any somatostatin analogue except for the following washout period

• Short-acting analogs of somatostatin can be used up to 24 hours before injection of [68Ga]Ga-DOTA-TATE.

• Long-acting analogs of somatostatin can be used up to 28 days before injection of [68Ga]Ga-DOTA-TATE.

5. Prior administration of a radiopharmaceutical unless 10 or more half-lives have elapsed before injection of [68Ga]Ga-DOTA-TATE

6. Use of other investigational drugs within 30 days before screening

7. Participants who are pregnant.

8. Participants who are lactating.

Related Conditions & MeSH terms

• Neoplasms
• Neuroendocrine Neoplasms
• Neuroendocrine Tumors

Intervention

Drug:
• [68Ga]Ga-DOTA-TATE
Single intravenous injection of [68Ga]Ga-DOTA-TATE determined by body weight (2 Mega-Becquerel (MBq) / kilogram (kg) (0.054 Millicurie (mCi)/kilogram (kg)) of body weight up to a maximum total dose of 200 MBq (5.4 mCi)) at the imaging day (Day 1).
• 68Ge/68Ga Generator
Radionuclide generator

Locations

Country	Name	City	State
Japan	Novartis Investigative Site	Kanazawa-city	Ishikawa
Japan	Novartis Investigative Site	Kyoto
Japan	Novartis Investigative Site	Sapporo city	Hokkaido

Sponsors (2)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals	Eckert & Ziegler Radiopharma GmbH

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of [68Ga]Ga-DOTA-TATE positive participants (TP participants) among CIM positive participants (TP or FN participants)	Subject-level sensitivity is defined as the proportion of [68Ga]Ga-DOTA-TATE PET/CT imaging positive participants (i.e. TP participants) among CIM positive participants (i.e. TP or FN participants).	Day 1
Primary	Proportion of [68Ga]Ga-DOTA-TATE negative participants (TN participants) among CIM negative participants (TN or FP participants)	Subject-level specificity is defined as the proportion of [68Ga]Ga-DOTA-TATE PET/CT imaging negative participants (i.e. TN participants) among CIM negative participants (i.e. TN or FP participants).	Day 1
Secondary	Proportion of participants who are positive on both [68Ga]Ga-DOTA-TATE PET/CT imagings and CIM (TP participants) among participants who are positive on [68Ga]Ga-DOTA TATE PET/CT imaging (TP or FP participants)	Subject-level positive predictive values (PPV) is defined as the proportion of TP participants among [68Ga]Ga-DOTA-TATE PET/CT imaging positive participants (i.e. TP or FP participants).	Day 1
Secondary	Proportion of participants who are negative on both [68Ga]Ga-DOTA-TATE PET/CT imaging and CIM (TN participants) among participants who are negative on [68Ga]Ga-DOTA-TATE PET/CT imaging (TN or FN participants)	Subject-level negative predictive values (NPV) is defined as the proportion of TN participants among [68Ga]Ga-DOTA-TATE PET/CT imaging negative participants (i.e. TN or FN participants).	Day 1
Secondary	Proportion of participants who have consistent results (i.e. TP or TN participants) among all participants assessed by [68Ga]Ga-DOTA-TATE PET/CT imaging and CIM	Subject-level accuracy is defined as the proportion of TP and TN participants among all patients in the EFF (i.e. TP+TN+FP+FN participants).	Day 1
Secondary	Proportion of [68Ga]Ga-DOTA-TATE positive regions (TP regions) among CIM positive regions (TP or FN regions)	Region-level sensitivity is defined as the proportion of [68Ga]Ga-DOTA-TATE PET/CT imaging positive regions (TP regions) among CIM positive regions (i.e. TP or FN regions).	Day 1
Secondary	Proportion of [68Ga]Ga-DOTA-TATE negative regions (TN regions) among CIM negative regions (TN or FP regions)	Region-level specificity is defined as the proportion of [68Ga]Ga-DOTA-TATE PET/CT imaging negative regions (TN regions) among CIM negative regions (i.e. TN or FP regions).	Day 1
Secondary	Proportion of regions which are positive on both [68Ga]Ga-DOTA-TATE PET/CT imaging and CIM (TP regions) among regions which are positive on [68Ga]Ga-DOTA-TATE PET/CT imaging (TP or FP regions)	Region-level (PPV) is defined as the proportion of regions which are positive on both [68Ga]Ga-DOTA-TATE PET/CT imaging and CIM (TP regions) among [68Ga]Ga-DOTA-TATE PET/CT imaging positive regions (i.e. TP or FP regions).	Day 1
Secondary	Proportion of regions who are negative on both [68Ga]Ga-DOTA-TATE PET/CT imaging and CIM (TN regions) among regions which are negative on [68Ga]Ga-DOTA-TATE PET/CT imaging (TN or FN regions)	Region-level (NPV) is defined as the proportion of regions which are negative on both [68Ga]Ga- DOTA-TATE PET/CT imaging and CIM (TN regions) among [68Ga]Ga-DOTA-TATE PET/CT imaging negative regions (i.e. TN or FN regions).	Day 1
Secondary	Proportion of regions which have consistent results (i.e. TP or TN regions) among all regions assessed by [68Ga]Ga-DOTA-TATE PET/CT imaging and CIM	Region-level accuracy is defined as the proportion of regions which are CIM and [68Ga]Ga-DOTA-TATE PET/CT imaging positive (TP regions) or negative (TN regions) among regions detected by CIM and [68Ga]Ga-DOTA-TATE PET/CT imaging (i.e. TP+TN+FP+FN regions).; Where TP, FP, TN, FN regions are defined as follows: TP regions are the regions which show at least one lesion based on both [68Ga]Ga-DOTATATE PET/CT imaging and CIM by central read.; FP regions are the regions which show at least one lesion based on [68Ga]Ga-DOTATATE PET/CT imaging but do not show any lesion based on CIM by central read.; TN regions are the regions which do not show any lesion based on both [68Ga]Ga-DOTATATE PET/CT imaging and CIM by central read.; FN regions are the regions which do not show any lesion based on [68Ga]Ga-DOTATATE PET/CT imaging but show at least one lesion based on CIM by central read.	Day 1
Secondary	Number of lesions detected by [68Ga]Ga-DOTA-TATE PET/CT imaging and each CIM at region-level	For region-level, number of lesion detected by [68Ga]Ga-DOTA-TATE PET/CT imaging and CIM will be counted.; Regarding [68Ga]Ga-DOTA-TATE PET/CT imaging, individual and mean number of lesions detected by each 3 central readers will be presented. Regarding CIM, each number of lesions detected by [111In]In-Pentetreotide SPECT/CT and High Resolution CT with contrast (or MRI if CT with contrast is medically contraindicated) will be presented.	Day 1
Secondary	Percentage of patients who underwent a change in intended treatment plan attributed to the [68Ga]Ga-DOTA-TATE PET/CT imaging as assessed by pre and post imaging questionnaires	Numbers and percentages of participants for each intended treatment plan collected from physician at pre and post [68Ga]Ga-DOTA-TATE PET/CT imaging will be summarized.; Summary statistics of participants for the change of intended treatment plan will also be presented.	Day 1
Secondary	Inter-reader agreement on [68Ga]Ga-DOTA-TATE PET/CT imaging	Inter-reader variability for [68Ga]Ga-DOTA-TATE PET/CT imaging is defined as agreement rate among reader determinations and will be assessed by Fleiss' Kappa statistics. Inter-reader variability (%) and its normality 95% CI will be presented.	Day 1
Secondary	Lesion-level concordance rate for SSTR between [68Ga]Ga-DOTA-TATE PET/CT imaging local read and local histopathology result among lesions that local histopathology result are available	The lesion-level concordance rate for SSTR between [68Ga]Ga-DOTA-TATE PET/CT imaging local read and local histopathology result among legions which is available, will be calculated. The rate is defined as the proportion of lesions which are positive or negative on both local read of [68Ga]Ga-DOTA-TATE PET/CT imaging and local histopathology among lesions detected by local histopathology.	Day 1 to Day 30
Secondary	Incidence of Treatment emergent adverse event (TEAE) within 8 days after [68Ga]Ga-DOTATATE administration	The incidence of treatment-emergent adverse events (new or worsening from baseline) will be summarized by system organ class and or preferred term, severity (based on CTCAE grades), type of adverse event, relation to study treatment.	Day1 to Day 8
Secondary	Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of [68Ga]Ga-DOTA-TATE	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUC(0-inf) will be listed and summarized using descriptive statistics.	Day 1 (Pre-dose, 5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)
Secondary	Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of [68Ga]Ga-DOTA-TATE	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUClast will be listed and summarized using descriptive statistics.	Day 1 (Pre-dose, 5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)
Secondary	Observed maximum plasma concentration (Cmax) of [68Ga]Ga-DOTA-TATE	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.	Day 1 (Pre-dose, 5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)
Secondary	Time of maximum observed drug concentration occurrence (Tmax) of [68Ga]Ga-DOTA-TATE	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.	Day 1 (Pre-dose, 5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)
Secondary	Terminal elimination half-life (T1/2) of [68Ga]Ga-DOTA-TATE	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. The half-live will be listed and summarized using descriptive statistics.	Day 1 (Pre-dose, 5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)
Secondary	Total systemic clearance for intravenous administration (CL) of [68Ga]Ga-DOTA-TATE	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics.	Day 1 (Pre-dose, 5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)
Secondary	Volume of distribution during the terminal phase following intravenous elimination (Vz) of [68Ga]Ga-DOTA-TATE	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics.	Day 1 (Pre-dose, 5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)