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

Novartis Pharmaceuticals71 enrolled

Overview

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.

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

Allocation

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

Conditions

Neuroendocrine Neoplasms

Interventions

[68Ga]Ga-DOTA-TATEDRUG

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 GeneratorDRUG

Radionuclide generator

Eligibility

Sex: ALLMin age: 18 YearsMax age: 100 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (8)

Novartis Investigative Site

Kashiwa, Chiba, Japan

Novartis Investigative Site

Sapporo, Hokkaido, Japan

Novartis Investigative Site

Kanazawa, Ishikawa-ken, Japan

Novartis Investigative Site

Yokohama, Kanagawa-ku, Japan

Outcomes

Primary Outcomes

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 \[TN\]

Time frame: 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 \[TN\]

Time frame: 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)

Time frame: 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).

Data from ClinicalTrials.gov

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Secondary Outcomes

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).

Time frame: 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).

Time frame: 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)

Time frame: 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)

Time frame: 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).

Time frame: 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)

Time frame: 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.

Time frame: 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)

Time frame: 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.

Time frame: 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).

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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.