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

March 22, 2024 updated by: Novartis Pharmaceuticals

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 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

70

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Novartis Pharmaceuticals

Study Contact Backup

Study Locations

  • Japan
      • Kyoto, Japan, 606 8507
        • Recruiting
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Time Frame: 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).
Day 1
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)
Time Frame: 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).
Day 1
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
Time Frame: 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).
Day 1
Proportion of [68Ga]Ga-DOTA-TATE positive regions (TP regions) among CIM positive regions (TP or FN regions)
Time Frame: 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).
Day 1
Proportion of [68Ga]Ga-DOTA-TATE negative regions (TN regions) among CIM negative regions (TN or FP regions)
Time Frame: 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).
Day 1
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)
Time Frame: 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).
Day 1
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)
Time Frame: 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).
Day 1
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
Time Frame: 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.
Day 1
Number of lesions detected by [68Ga]Ga-DOTA-TATE PET/CT imaging and each CIM at region-level
Time Frame: 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.
Day 1
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
Time Frame: 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.
Day 1
Inter-reader agreement on [68Ga]Ga-DOTA-TATE PET/CT imaging
Time Frame: 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.
Day 1
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
Time Frame: 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.
Day 1 to Day 30
Incidence of Treatment emergent adverse event (TEAE) within 8 days after [68Ga]Ga-DOTATATE administration
Time Frame: 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.
Day1 to Day 8
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of [68Ga]Ga-DOTA-TATE
Time Frame: 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.
Day 1 (Pre-dose, 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
Time Frame: 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.
Day 1 (Pre-dose, 5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)
Observed maximum plasma concentration (Cmax) of [68Ga]Ga-DOTA-TATE
Time Frame: 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.
Day 1 (Pre-dose, 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
Time Frame: 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.
Day 1 (Pre-dose, 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
Time Frame: 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.
Day 1 (Pre-dose, 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
Time Frame: 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.
Day 1 (Pre-dose, 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
Time Frame: 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.
Day 1 (Pre-dose, 5 min, 15 min, 30 min, 45 min, 60 min, 120 min, 180 min)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Collaborators

Eckert & Ziegler Radiopharma GmbH

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 21, 2024

Primary Completion (Estimated)

July 3, 2025

Study Completion (Estimated)

July 3, 2025

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)

March 25, 2024

Last Update Submitted That Met QC Criteria

March 22, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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