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Clinical Trials in the UK / NCT03972488
Active, not recruiting Phase 3

Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET

NCT03972488 · tracked via the Priya Life Science UK tracker
Sponsor
Advanced Accelerator Applications
Phase
Phase 3
Started
2020-01-08
Last updated
2026-01-21

Condition(s) studied

Gastro-enteropancreatic Neuroendocrine Tumor

Investigational drug(s) / intervention(s)

Lutathera30 mg Octreotide long acting repeatable (LAR) (Sandostatin LAR Depot)2.5% Lys-Arg sterile amino acid solutionHigh dose 60 mg octreotide long-acting repeatable

Lutathera: Lutathera is a sterile radiopharmaceutical supplied as a ready-to-use solution for infusion containing 177Lu-DOTA0-Tyr3-octreotate as a drug substance with a volumetric activity of 370 MBq/mL at reference date and time (calibration time). Each Lutathera infusion continued for 30 min.

30 mg Octreotide long acting repeatable (LAR) (Sandostatin LAR Depot): Sandostatin® LAR Depot (octreotide LAR) is a pharmaceutical that was available in single-use kits containing a 6-mL vial of 10 mg, 20 mg, or 30 mg strength for intramuscular injection, a syringe containing 2.5 mL of diluent, two sterile 1½" 19-gauge needles, and two alcohol wipes.

2.5% Lys-Arg sterile amino acid solution: Participants who received Lutathera were administered a concomitant 2.5% Lys-Arg solution for kidney protection, with each Lutathera dose. The 2.5% Lys-Arg solution was administered intravenously for 4 hours (infusion rate: 250 ml/h); the infusion was to start 30 minutes prior to the start of the Lutathera infusion and continue during (30 min) and up to at least 3 hours after the Lutathera infusion.

High dose 60 mg octreotide long-acting repeatable: Sandostatin® LAR Depot (octreotide LAR) is a pharmaceutical that was available in single-use kits containing a 6-mL vial of 10 mg, 20 mg, or 30 mg strength for intramuscular injection, a syringe containing 2.5 mL of diluent, two sterile 1½" 19-gauge needles, and two alcohol wipes.

Study summary

The aim of NETTER-2 was to determine if Lutathera in combination with long-acting octreotide prolongs progression free survival (PFS) in gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients with high proliferation rate tumors (G2 and G3), when given as a first line treatment compared to treatment with high dose (60 mg) long-acting octreotide. Somatostatin analog (SSA) naive patients were eligible, as well as patients previously treated with SSAs in the absence of progression.

Eligibility

Sex
ALL
Min age
18 Years
Max age
Healthy volunteers
No
Inclusion Criteria: * Presence of metastasized or locally advanced, inoperable (curative intent) histologically proven, well differentiated Grade 2 or Grade 3 gastroenteropancreatic neuroendocrine (GEP-NET) tumor diagnosed within 6 months prior to screening. * Ki67 index ≥10 and ≤ 55% * Patients ≥ 15 years of age and a body weight of \> 40 kg at screening * Expression of somatostatin receptors on all target lesions documented by CT/MRI scans, assessed by any of the following somatostatin receptor imaging (SRI) modalities within 3 months prior to randomization: \[68Ga\]-DOTA-TOC (e.g. Somakit-TOC®) PET/CT (or MRI when applicable based on target lesions) imaging, \[68Ga\]-DOTA-TATE PET/CT (or MRI when applicable based on target lesions) imaging (e.g. NETSPOT®), Somatostatin Receptor scintigraphy (SRS) with \[111In\]-pentetreotide (Octreoscan® SPECT/CT), SRS with \[99mTc\]-Tektrotyd, \[64Cu\]-DOTA-TATE PET/CT (or MRI when applicable based on target lesions) imaging. * The tumor uptake observed in the target lesions must be \> normal liver uptake. * Karnofsky Performance Score (KPS) ≥ 60 * Presence of at least 1 measurable site of disease * Patients who have provided a signed informed consent form to participate in the study, obtained prior to the start of any protocol related activities Exclusion Criteria: * Creatinine clearance \< 40 mL/min calculated by the Cockroft Gault method * Hb concentration \< 5.0 mmol/L (\<8.0 g/dL); WBC \< 2x10E9/L (2000/mm3); platelets \< 75x10E9/L (75x10E3/mm3) * Total bilirubin \> 3 x ULN * Serum albumin \< 3.0 g/dL unless prothrombin time is within the normal range * Pregnancy or lactation * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, are not allowed to participate in this study UNLESS they are using highly effective methods of contraception throughout the study treatment period (including cross-over and re-treatment, if applicable) and for 7 months after study drug discontinuation * Peptide receptor radionuclide therapy (PRRT) at any time prior to randomization in the study. * Documented RECIST progression to previous treatments for the current GEP-NET at any time prior to randomization * Patients for whom in the opinion of the investigator other therapeutic options (eg chemo-, targeted therapy) are considered more appropriate than therapy offered in the study, based on patient and disease characteristics * Any previous therapy with Interferons, Everolimus (mTOR-inhibitors), chemotherapy or other systemic therapies for GEP-NET administered for more than 1 month or within 12 weeks prior to randomization in the study. * Any previous radioembolization, chemoembolization and radiofrequency ablation for GEP-NET * Any surgery within 12 weeks prior to randomization in the study * Known brain metastases, unless these metastases have been treated and stabilized for at least 24 weeks, prior to screening in the study. Patients with a history of brain metastases must have a head CT or MRI with contrast to document stable disease prior to randomization in the study. * Uncontrolled congestive heart failure (NYHA II, III, IV). Patients with history of congestive heart failure who do not violate this exclusion criterion will undergo an evaluation of their cardiac ejection fraction prior to randomization via echocardiography. The results from an earlier assessment (not exceeding 30 days prior to randomization) may substitute the evaluation at the discretion of the Investigator, if no clinical worsening is noted. The patient's measured cardiac ejection fraction in these patients must be ≥40% before randomization. * QTcF \> 470 msec for females and QTcF \> 450 msec for males or congenital long QT syndrome * Uncontrolled diabetes mellitus as defined by hemoglobin A1c value \> 7.5% * Hyperkaleamia \> 6.0 mmol/L (CTCAE Grade 3) which is not corrected prior to study enrolment * Any patient receiving treatment with short-acting octreotide, which cannot be interrupted for 24 h before and 24 h after the administration of Lutathera, or any patient receiving treatment with SSAs (e.g. octreotide long-acting), which cannot be interrupted for at least 6 weeks before the administration of Lutathera. * Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with the completion of the study. * Prior external beam radiation therapy to more than 25% of the bone marrow. * Current spontaneous urinary incontinence * Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and proven no evidence of recurrence for 5 years * Patient with known incompatibility to CT Scans with IV contrast due to allergic reaction or renal insufficiency. If such a patient can be imaged with MRI, then the patient would not be excluded. * Hypersensitivity to any somatostatin analogues, the IMPs active substance or to any of the excipients. * Patients who have participated in any therapeutic clinical study/received any investigational agent within the last 30 days

Primary outcome measure(s)

Trial sites (40)

FacilityCityRegionStatus
Yale Cancer Center New Haven Connecticut
USF - H. Lee Moffitt Cancer Center and Research Institute Tampa Florida
University of Iowa Hospitals and Clinics - Oncology Iowa City Iowa
University of Kentucky UK Markey Cancer Center Lexington Kentucky
Mayo Clinic - Oncology Rochester Minnesota
MD Anderson Cancer Center Houston Texas
London Health Sciences Centre, University of Western Ontario - Oncology London Canada
Centre Hospitalier Universitaire de Quebec Québec Canada
Sunnybrook Health Sciences Centre Toronto Canada
BC Cancer Agency Vancouver Canada
CHU Paris Nord-Val de Seine Clichy France
Hospices Civils de Lyon (HCL) - Hopital Edouard Herriot Lyon France
Institut du Cancer de Montpellier - Oncology Montpellier France
CHU-Hôtel Dieu Service de Médecine Nucléaire Nantes France
Institut Gustave Roussy Villejuif France
Universitätsklinikum Erlangen Erlangen Germany
Universitätsklinikum Essen - Klinik für Nuklearmedizin Essen Germany
A.O.di Bologna Policl.S.Orsola Bologna Italy
University of Genova - Oncology Genova Italy
Istituto Oncologico Romagnolo Meldola Italy
Fondazione Irccs Istituto Nazionale Tumori Milan Italy
Ieo, Irccs Milan Italy
IRCCS fondazione Pascale - Oncology Naples Italy
Arcispedale Santa Maria Nuova, Reggio Emilia - Oncology Reggio Emilia Italy
Azienda Ospedaliera Sant'Andrea - Università La Sapienza U.O.C. Mal App. Digerente e - Oncology Roma Italy
Erasmus Medisch Centrum Rotterdam Netherlands
UMC Utrecht - Oncology Utrecht Netherlands
Seoul National University Bundang Hospital Seongnam-si South Korea
Asan Medical Center - Oncology Seoul South Korea
Seoul National University Hospital - Department of Internal Medicine Seoul South Korea
Severance Hospital, Yonsei University Health System - Medical Oncology Seoul South Korea
Hospital Universitario Vall d'Hebrón Barcelona Spain
Hospital General Universitario Gregorio Marañón Madrid Spain
Hospital Universitario Ramón y Cajal Madrid Spain
Hospital Universitari i Politecnic La Fe Valencia Spain
Bristol Haematology and Oncology Centre Bristol United Kingdom
Guys And St Thomas Hospital London United Kingdom
Kings College Hospital - Oncology London United Kingdom
Royal Free Hospital, London London United Kingdom
Weston Park Hospital Sheffield United Kingdom

More Advanced Accelerator Applications trials in the UK

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT03972488 on ClinicalTrials.gov ↗ ← All trials in the UK