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

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

The purpose of this study was 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 was collected in order to provide the evidence for diagnosis of [68Ga]Ga-DOTA-TATE PET/CT imaging in patient with NENs in Japan.

Study Overview

• Status: Completed
• Conditions: Neuroendocrine Neoplasms
• Intervention / Treatment: Drug: [68Ga]Ga-DOTA-TATE; Drug: 68Ge/68Ga Generator

Detailed Description

A total of 71 participants (48 patients with confirmed/suspected NENs and 23 HVs) were enrolled to ensure that at least 70 participants (47 patients with confirmed/suspected NENs and 23 HVs) were evaluable for the co-primary endpoints. All enrolled participants were administered [68Ga]Ga-DOTA-TATE and PET/CT scan.

The co-primary endpoints of the subject-level sensitivity and the subject-level specificity were assessed by comparing the central reading results of the [68Ga]Ga-DOTA-TATE PET/CT scan to the central reading results of Conventional imaging (CIM).

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 8128582
    • Novartis Investigative Site
  • Fukuoka, Japan, 813-0017
    • Novartis Investigative Site
  • Kyoto, Japan, 6068507
    • Novartis Investigative Site
  • Chiba
    • Kashiwa, Chiba, Japan, 277 8577
      • Novartis Investigative Site
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060 8648
      • Novartis Investigative Site
  • Ishikawa-ken
    • Kanazawa, Ishikawa-ken, Japan, 920 8641
      • Novartis Investigative Site
  • Kanagawa-ku
    • Yokohama, Kanagawa-ku, Japan, 236-0004
      • Novartis Investigative Site
  • Tokyo
    • Chuo Ku, Tokyo, Japan, 1040045
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

1. Signed informed consent must have been obtained prior to participation in the study
2. Participants must have been adults >= 18 years of age
3. ECOG performance status 0-2
4. For patient with NENs only: Participants were to be confirmed NENs based on histopathology, imaging and other relevant examination, or with suspected NENs which localization could not have been 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 havehad 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 were pregnant.
8. Participants who were lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [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)	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).; Other Names: AAA501; Drug: 68Ge/68Ga Generator; Radionuclide generator; Other Names: EZR001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number 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).; TP participants were those who showed at least one lesion based on both [68Ga]Ga-DOTA-TATE PET/CT imaging and CIM by central read.; FN participants were those who did not show any lesions based on [68Ga]Ga-DOTA-TATE PET/CT imaging but showed at least one lesion based on CIM by central read. True Positive [TP] False Positive [FP] False Negative [FN] True Negative [TN]	Day 1
Number 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).; TN participants were those who did not show any lesions based on both [68Ga]Ga-DOTA-TATE PET/CT imaging and CIM by central read.; FP participants were those who showed at least one lesion based on [68Ga]Ga-DOTA-TATE PET/CT imaging but did not show any lesions based on CIM by central read. True Positive [TP] False Positive [FP] False Negative [FN] True Negative [TN]	Day 1
Subject-level Sensitivity	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). True Positive [TP] False Positive [FP] False Negative [FN] True Negative [TN] Sensitivity = TP / (TP + FN)	Day 1
Subject-level Specificity	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). True Positive [TP] False Positive [FP] False Negative [FN] True Negative [TN] Specificity = TN / (TN + FP).	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number 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
Number 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 NPV was 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
Subject-level PPV	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). PPV (Subject-level positive predictive values) = TP / (TP + FP)	Day 1
Subject-level NPV	Subject-level NPV was defined as the proportion of TN participants among [68Ga]Ga-DOTA-TATE PET/CT imaging negative participants (i.e. TN or FN participants). NPV (Subject-level negative predictive values) = TN / (TN + FN)	Day 1
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	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). Accuracy = (TP + TN) / (TP + TN + FP + FN).	Day 1
Region-level Sensitivity	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). Sensitivity = TP / (TP + FN)	Day 1
Region-level Specificity	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). Specificity = TN / (TN + FP) Note: Even when a participant is categorized as positive in subject-level, he/she can still have negative results in region-level. e.g. When only Liver is positive and other regions are negative, the participant is categorized as positive in subject-level. As all participants had at least one CIM-negative region and were included in the table, the number of participants analyzed is 71.	Day 1
Region-level Positive Predictive Values (PPV)	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). Region-level positive predictive values (PPV) = TP / (TP +FP)	Day 1
Region-level Negative Predictive Values (NPV)	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). Region-level negative predictive values (NPV) = TN / (TN + FN) Note: Even when a participant is categorized as positive in subject-level, he/she can still have negative results in region-level. e.g. When only Liver is positive and other regions are negative, the participants is categorized as positive in subject-level. As all participants had at least one negative region by Ga-DOTA-TATE PET/CT and were included in the table, the number of participants analyzed = 71.	Day 1
Region-level Accuracy	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). Accuracy = (TP + TN) / (TP + TN + FP + FN).	Day 1
Region-level True Positive	TP regions were the regions which showed at least one lesion based on both [68Ga]Ga-DOTA-TATE PET/CT imaging and CIM by central read	Day 1
Region-level False Negative	FN regions were the regions which did not show any lesions based on [68Ga]Ga-DOTA-TATE PET/CT imaging but show at least one lesion based on CIM by central read.	Day 1
Region-level False Positive	FP regions were the regions which showed at least one lesion based on [68Ga]Ga-DOTA-TATE PET/CT imaging but do not showed any lesion based on CIM by central read.	Day 1
Region-level True Negative	TN regions were the regions which did not show any lesion based on both [68Ga]Ga-DOTA-TATE PET/CT imaging and CIM by central read.	Day 1
Number of Participants 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 of participants for each intended treatment plan collected from physician at pre and post [68Ga]Ga-DOTA-TATE PET/CT imaging will be summarized.	Before and after imaging on Day 1
Inter-reader Agreement on [68Ga]Ga-DOTA-TATE PET/CT Imaging	The assessment of [68Ga]Ga-DOTA-TATE PET/CT images set was compared among the 3 independent readers.	Day 1
Inter-reader Variability (%) 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. As assessed by Fleiss' Kappa statistics. Inter-reader variability (%) and its normality 95% CI is presented.	Day 1
Incidence of Treatment Emergent Adverse Event (TEAE) Within 8 Days After [68Ga]Ga-DOTATATE Administration	An adverse event (AE) is any untoward medical occurrence (e.g., any occurrence of unfavorable and unintended sign(s), symptom(s) or medical condition, including abnormal laboratory findings, or worsening of any pre-existing sign(s), symptom(s) or medical condition) in a participant after providing written informed consent for participation in the study. Therefore, an AE may or may not be temporally or causally associated with the use of any treatment used in this study. This includes events reported by the participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally authorized representative).	For treated pts: AEs are reported from the single dose of study treatment plus 8 days post treatment, up to a maximum timeframe of 9 days. For HV pts: AEs are reported from the study start plus 8 days, up to a maximum timeframe of 9 days.
Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUCinf) of [68Ga]Ga-DOTA-TATE [Mass-based Concentration]	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 (5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)
Area Under the Serum Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of [68Ga]Ga-DOTA-TATE [Mass-based Concentration]	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUClast will be listed and summarized using descriptive statistics.	Day 1 (5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)
Observed Maximum Plasma Concentration (Cmax) of [68Ga]Ga-DOTA-TATE [Mass-based Concentration]	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.	Day 1 (5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)
Time of Maximum Observed Drug Concentration Occurrence (Tmax) of [68Ga]Ga-DOTA-TATE [Mass-based Concentration]	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.	Day 1 (5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)
Terminal Elimination Half-life (T1/2) of [68Ga]Ga-DOTA-TATE [Mass-based Concentration]	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 (5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)
Total Systemic Clearance for Intravenous Administration (CL) of [68Ga]Ga-DOTA-TATE [Mass-based Concentration]	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics.	Day 1 (5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)
Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) of [68Ga]Ga-DOTA-TATE [Mass-based Concentration]	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics.	Day 1 (5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)
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
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 - Concordance Rate	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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Collaborators: Eckert & Ziegler Radiopharma GmbH
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Novartis Clinical Trial Results

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2024
• Primary Completion (Actual): December 27, 2024
• Study Completion (Actual): December 27, 2024

Study Registration Dates

• First Submitted: January 26, 2024
• First Submitted That Met QC Criteria: January 26, 2024
• First Posted (Actual): February 5, 2024

Study Record Updates

• Last Update Posted (Actual): February 3, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: PET/CT; Positron Emission Tomography (PET); Sensitivity; Specificity; Diagnostic performance; [68Ga]Ga-DOTA-TATE; Neuroendocrine Neoplasms (NENs); Computerized Tomography (CT)
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity
• Other Study ID Numbers: CAAA501A11301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No