Italian Prospective Observational Study Assessing the Effectiveness and Outcomes Associated With Lutathera Treatment in GEP-NETs

Study Overview
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Brief Summary
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This is a multicentre long-term non-interventional study of adult subjects diagnosed with unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive GEP-NETs who have been prescribed Lutathera® in standard clinical practice.

Detailed Description
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Data on patients will be collected from the date when patient consent was obtained, during treatment with Lutathera® and for a follow-up period until end of study (EOS), defined as the time when the last enrolled patient has completed 36 months of assessments (unless early termination) after enrolment. Data will be collected in accordance with routine clinical visits. The study duration will be 48 months in total: 12 months recruitment and 36 of follow-up from the last patient in.

Official Title
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Two Steps Italian Prospective obsErvationAL Study Assessing the Effectiveness and Outcomes Associated With LUtathera (177Lu) Oxodotreotide Treatment in Adult Subjects With Unresectable or Metastatic, Progressive, Well Differentiated (G1 and G2), Somatostatin Receptor Positive Gastroenteropancreatic-neuroendocrine Tumours (GEP-NETs) - REAL-LU

Conditions
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Gastroenteropancreatic Neuroendocrine Tumor

Intervention / Treatment
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* Drug: Lutathera®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained prior to any data collection. Patients must be diagnosed with unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic-neuroendocrine tumour (GEP-NET). Aged ≥18 years. Patients must be naïve to treatment with Lutathera® at enrolment. Exclusion Criteria: Participation in a current or prior investigational study within 30 days preceding enrolment or within 5 half-lives of the investigational product, whichever is longer.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lutathera®<br>Lutathera® will be administered according to the local label and according to the recommended treatment regimen in adults consisting of four equally divided doses of Lutathera® for a total of 29.6 GBq (800 mCi). | Drug: Lutathera®<br>* Treatment with Lutathera® will be independent from participation in this observational study and must not be initiated for the purpose of participating in this study. The decision to treat patients with Lutathera® will occur before patients are enrolled in the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS, defined as the time, in months, from Lutathera® treatment initiation to the date of first objective tumour progression, determined according to Response Evaluation Criteria in Solid Tumours (RECIST) Criteria, Version 1.1, or death due to any cause, whichever comes first. | Up to 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR, defined as the proportion of treated patients who achieve a best overall response of partial response (PR) or complete response (CR) according to RECIST 1.1 | Up to 48 months | 
| Duration of Response (DoR), for those patients who achieve a best response of PR or better | DoR, defined as the time, in months, from the date when criteria for response are first met until the date of a progression event (according to the primary definition of PFS). | Up to 48 months | 
| Clinical Benefit Rate (CBR) | CBR, defined as the proportion of treated patients who achieve a best overall response of stable disease (SD), PR or CR according to RECIST 1.1. | Up to 48 months | 
| Duration of Clinical Benefit, for those patients who achieve a best response of SD or better | Duration of clinical benefit, defined as the time, in months, from the date when criteria for clinical benefit are first met until the date of a progression event (according to the primary definition of PFS). | Up to 48 months | 
| Time to Progression (TTP) | TTP, defined as the time, in months, from Lutathera® treatment initiation to the date of first objective tumour progression, assessed according to RECIST 1.1. | Up to 48 months | 
| Assess the impact of treatment on health-related Quality of Life (HRQoL) by EORTC QLQ-C30 questionnaire | EORTC QLQ-C30 will be filled in by the patient prior to knowing computed tomography (CT) scan/magnetic resonance imaging (MRI) result. The EORTC QLQ-C30 questionnaire is designed for use with a wide range of cancer patient populations and is intended to be supplemented by tumour-specific questionnaire modules. The EORTC QLQ-C30 incorporates different multi-item scales, i.e. functional scales, symptom scales and a Global Health Status/QoL scale. All parameters are evaluated using single or multi-item questions which are consequently converted into a 100-point score. | Up to 48 months | 
| Assess the impact of treatment on health-related Quality of Life (HRQoL) by EORTC QLQ-G.I.NET-21 questionnaire | EORTC QLQG. I.NET-21 will be filled in by the patient prior to knowing computed tomography (CT) scan/magnetic resonance imaging (MRI) result. EORTC QLQ-G.I.NET-21 questionnaire is a module specific for neuroendocrine tumours and comprises 21 questions assessing disease symptoms, side effects of treatment, body image, disease related worries, social functioning, communication and sexuality. Each subscale is based on the following items: endocrine scale (items 31-33); gastrointestinal scale (34-38); treatment scale (39, 40, and 46); social function scale (42, 44, and 49); disease related worries scale (41, 43, and 47); muscle/bone pain (48), sexual function (51), information/communication function (50), and body image (45). All parameters are evaluated using single or multi-item questions which are consequently converted into a 100-point score | Up to 48 months | 
| Time to Deterioration (TTD) in global health scale (TTD- global health scale) | TTD, defined as the time, in months, from Lutathera® treatment initiation to the date of first deterioration of ≥10 points in the EORTC QLQ-C30 and EORTC QLQ-G.I.NET21 global health scale score compared to the baseline score for the same domain. | Baseline, up to 48 months | 
| Time to Deterioration (TTD) in diarrhoea item (TTD- diarrhoea item) | TTD, defined as the time, in months, from Lutathera® treatment initiation to the date of first deterioration of ≥10 points in the EORTC QLQ-C30 and EORTC QLQ-G.I.NET21 diarrhoea item score compared to the baseline score for the same domain. | Baseline, up to 48 months | 
| Time to Deterioration (TTD) in fatigue item (TTD- fatigue item) | TTD, defined as the time, in months, from Lutathera® treatment initiation to the date of first deterioration of ≥10 points in the EORTC QLQ-C30 and EORTC QLQ-G.I.NET21 fatigue item score compared to the baseline score for the same domain. | Baseline, up to 48 months | 
| Time to Deterioration (TTD) in pain item (TTD- pain item) | TTD, defined as the time, in months, from Lutathera® treatment initiation to the date of first deterioration of ≥10 points in the EORTC QLQ-C30 and EORTC QLQ-G.I.NET21 pain item score compared to the baseline score for the same domain. | Baseline, up to 48 months | 
| Number of patients with Adverse Events (AEs) related to study drug | Number of patients with Adverse Events (AEs) related to study drug will be reported | Up to 48 months | 
| Seriousness and relationship to Lutathera® treatment | Seriousness and relationship to Lutathera® treatment will be reported | Up to 48 months | 
| Incidence of deaths due to any cause. | Incidence of deaths due to any cause will be reported | Up to 48 months | 
| Number of participants with notable changes in laboratory parameters | Safety measured by the notable post-baseline changes in laboratory parameters compared to baseline. Standard Lab parameters will be reported when performed as clinical practice. | Up to 48 months | 
| Number of participants with notable changes in physical examination | Safety measured by the notable post-baseline changes in physical examination compared to baseline. Physical examination will be reported when performed as clinical practice. | Up to 48 months | 
| Number of participants with notable changes in vital signs | Safety measured by the notable post-baseline changes in vital signs compared to baseline. Vital signs will be reported when performed as clinical practice. | Up to 48 months | 
| Number of participants with notable changes in electrocardiogram (ECG) | Safety measured by the notable post-baseline changes in ECG compared to baseline. ECG results will be reported when performed as clinical practice. | Up to 48 months | 
| Changes in Karnofsky Performance Status (KPS) scores | KPS scores will be reported when performed as clinical practice. Karnofsky Performance Status (KPS) is a standard way of measuring the ability of cancer patients to perform ordinary tasks. The KPS score ranges from 0 to 100. A higher score means the patient is better able to carry out daily activities. KPS forms must be completed by the treating physician at each treatment and follow-up visit. | Up to 48 months | 
| Baseline characteristics of patients selected | Baseline characteristics of patients prescribed with Lutathera® (medical and disease history, prior treatments for NETs, baseline and demographic characteristics). | Baseline | 
| Correlation of possible prognostic factors with clinical effectiveness outcomes. | Potential prognostic factors (e.g., somatostatin receptor (SSTR) expression levels (tumour uptake score) determined by Octreoscan® scintigraphy or 68Ga PET/CT according to clinical practice, standardized uptake value (SUV) of [18F]fluorodeoxyglucose (FDG) PET/CT (if performed), levels of the biomarkers collected in clinical routine, stage of disease at the time of first diagnosis, KPS score at baseline). | Up to 48 months | 
| Describe radiation emission levels at one metre distance of patients treated | Radiation emission levels at one metre distance of patients treated with Lutathera® at the time of hospital discharge and as collected according to the local Summary of Product Characteristics (SmPC), the Scheda di Monitoraggio AIFA and as per clinical practice | Up to 18 months | 
| Describe dosimetry data after administration (if dosimetry is performed) | Number of patients undergoing dosimetry, dosimetry method used and radiation-absorbed doses to tumour and normal organs after Lutathera® administration. | Up to 18 months | 
| Number of days of hospitalization for Lutathera® treatment. | Number of days of hospitalization for Lutathera® treatment will be provided | Up to 18 months | 
| Frequency of hospitalization. | Frequency of hospitalizations will be provided | Up to 48 months | 
| Duration of hospitalization | Duration of hospitalizations will be provided | Up to 48 months | 
| Extent of usage of concomitant medications for AE treatment. | Extent of usage of concomitant medications for AE treatment will be provided | Up to 48 months | 
| Changes in use of concomitant medications for symptoms management | Changes in use of concomitant medications for symptoms management will be provided | Up to 48 months | 
| Information about the patient's diagnosis-related group (DRG) | Information about the patient's diagnosis-related group (DRG) will be provided | Up to 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GEP-NET, Gastro-Entero-Pancreatic, Neuroendocrine Tumour, AAA, Advanced Accelerator Applications, Luthatera