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

Phase 3

Completed

• Conditions: Neuroendocrine Neoplasms
• Interventions: Drug: [68Ga]Ga-DOTA-TATE; Drug: 68Ge/68Ga Generator

• Registration Number: NCT06240741
• Lead Sponsor: Novartis Pharmaceuticals

Brief 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.

Detailed 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)

Study Timeline

• Study First Submitted: 2024-01-26
• Study First Submitted QC: 2024-01-26
• Study First Posted: 2024-02-05
• Study Start: 2024-03-21
• Primary Completion: 2024-12-27
• Study Completion: 2024-12-27
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-17
• Last Update Posted: 2025-04-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 71

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
[68Ga]Ga-DOTA-TATE	68Ge/68Ga Generator	All eligible participants will receive \[68Ga\]Ga-DOTA-TATE via intravenous injection at a dose of 2 MBq/kg (0.054 mCi/kg) of body weight up to a maximum total dose of 200 MBq (5.4 mCi)
[68Ga]Ga-DOTA-TATE	[68Ga]Ga-DOTA-TATE	All eligible participants will receive \[68Ga\]Ga-DOTA-TATE via intravenous injection at a dose of 2 MBq/kg (0.054 mCi/kg) of body weight up to a maximum total dose of 200 MBq (5.4 mCi)

Primary Outcome Measures

Name	Time	Method
Proportion of [68Ga]Ga-DOTA-TATE negative participants (TN participants) among CIM negative participants (TN or FP participants)	Day 1	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).
Proportion of [68Ga]Ga-DOTA-TATE positive participants (TP participants) among CIM positive participants (TP or FN participants)	Day 1	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).

Secondary Outcome Measures

Name	Time	Method
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)	Day 1	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).
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	Day 1	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).
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)	Day 1	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).
Proportion of [68Ga]Ga-DOTA-TATE negative regions (TN regions) among CIM negative regions (TN or FP regions)	Day 1	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).
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)	Day 1	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).
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)	Day 1	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).
Inter-reader agreement on [68Ga]Ga-DOTA-TATE PET/CT imaging	Day 1	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.
Terminal elimination half-life (T1/2) of [68Ga]Ga-DOTA-TATE	Day 1 (Pre-dose, 5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. The half-live will be listed and summarized using descriptive statistics.
Proportion of [68Ga]Ga-DOTA-TATE positive regions (TP regions) among CIM positive regions (TP or FN regions)	Day 1	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).
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	Day 1	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.
Number of lesions detected by [68Ga]Ga-DOTA-TATE PET/CT imaging and each CIM at region-level	Day 1	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.
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	Day 1 to Day 30	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.
Time of maximum observed drug concentration occurrence (Tmax) of [68Ga]Ga-DOTA-TATE	Day 1 (Pre-dose, 5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.
Total systemic clearance for intravenous administration (CL) of [68Ga]Ga-DOTA-TATE	Day 1 (Pre-dose, 5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics.
Volume of distribution during the terminal phase following intravenous elimination (Vz) of [68Ga]Ga-DOTA-TATE	Day 1 (Pre-dose, 5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics.
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	Day 1	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.
Incidence of Treatment emergent adverse event (TEAE) within 8 days after [68Ga]Ga-DOTATATE administration	Day1 to Day 8	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.
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of [68Ga]Ga-DOTA-TATE	Day 1 (Pre-dose, 5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUC(0-inf) will be listed and summarized using descriptive statistics.
Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of [68Ga]Ga-DOTA-TATE	Day 1 (Pre-dose, 5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUClast will be listed and summarized using descriptive statistics.
Observed maximum plasma concentration (Cmax) of [68Ga]Ga-DOTA-TATE	Day 1 (Pre-dose, 5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇯🇵 Kyoto, Japan