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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Gastroenteropancreatic Neuroendocrine Tumor
• Intervention / Treatment: Drug: Lutathera®

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 164

Contacts and Locations

Study Locations

• Italy
  • Alessandria, Italy
    • Novartis Investigative Site
  • Bologna, Italy
    • Novartis Investigative Site
  • Brescia, Italy
    • Novartis Investigative Site
  • Cona, Italy
    • Novartis Investigative Site
  • Firenze, Italy
    • Novartis Investigative Site
  • Latina, Italy
    • Novartis Investigative Site
  • Meldola, Italy
    • Novartis Investigative Site
  • Messina, Italy
    • Novartis Investigative Site
  • Milano, Italy
    • Novartis Investigative Site
  • Napoli, Italy
    • Novartis Investigative Site
  • Negrar, Italy
    • Novartis Investigative Site
  • Padova, Italy
    • Novartis Investigative Site
  • Pisa, Italy
    • Novartis Investigative Site
  • Reggio Emilia, Italy
    • Novartis Investigative Site
  • Rionero In Volture, Italy
    • Novartis Investigative Site
  • Roma, Italy
    • Novartis Investigative Site
  • Rozzano, Italy
    • Novartis Investigative Site
  • Torino, Italy
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

The study plans to enroll patients with unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive GEP-NETs.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Lutathera®; 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®; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Advanced Accelerator Applications
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2021
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: November 20, 2020
• First Submitted That Met QC Criteria: January 25, 2021
• First Posted (Actual): January 27, 2021

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 4, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: AAA; Neuroendocrine Tumour; GEP-NET; Luthatera; Gastro-Entero-Pancreatic; Advanced Accelerator Applications
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Intestinal Diseases; Pancreatic Diseases; Stomach Neoplasms; Pancreatic Neoplasms; Neuroendocrine Tumors; Intestinal Neoplasms; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Lutetium Lu 177 dotatate
• Other Study ID Numbers: CAAA601A0IT02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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