A phase III multi-center, randomized, open-label study to evaluate the efficacy and safety of Lutathera in combination with best supportive care octreotide long-acting (30 mg), when given as a 1st line treatment in GEP-NET patients with high proliferation rate tumors (G2 and G3), in comparison to treatment with high dose (60 mg) octreotide long-acting.

A phase III multi-center, randomized, open-label study to evaluate the efficacy and safety of Lutathera in patients with Grade 2 and Grade 3 advanced GEP-NET. - NETTER-2

Status

Not yet recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2019-001562-15-DE

Enrollment

222

Registered

2019-06-14

Start date

Unknown

Completion date

Unknown

Last updated

2024-02-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Patients with somatostatin receptor positive, well-differentiated G2 and G3, advanced GEP NETs MedDRA version: 21.0 Level: PT Classification code 10052399 Term: Neuroendocrine tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10077559 Term: Gastroenteropancreatic neuroendocrine tumour disease System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps

Interventions

Trade Name: Lutathera 370 MBq/mL solution for infusion Product Name: Lutathera 370 MBq/mL solution for infusion Pharmaceutical Form: Solution for infusion INN or Proposed INN: LUTETIUM (177LU) OXODOTR

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. 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. 2. Ki67 index =10 and = 55%. 3. Patients =15 years of age and a body weight of >40 kg at screening. 4. 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 or [68Ga]-DOTA-TATE PET/CT (or MRI when applicable based on target lesions) imaging (e.g. NETSPOT®) or 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). 5. The tumor uptake observed in the target lesions must be > normal liver uptake observed on planar imaging. 6. Karnofsky Performance Score (KPS) =60. 7. Presence of at least 1 measurable site of disease. 8. Patients who have provided a signed informed consent form to participate in the study, obtained prior to the start of any protocol related activities. Are the trial subjects under 18? yes Number of subjects for this age range: 10 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 112

Exclusion criteria

Exclusion criteria: 1. Creatinine clearance 3 x ULN. 4. Serum albumin 40% before randomization. 15. QTcF > 470 msec for females and QTcF > 450 msec for males or congenital long QT syndrome. 16. Uncontrolled diabetes mellitus as defined by hemoglobin A1c value > 7.5%. 17. Hyperkaleamia >6.0 mmol/L (CTCAE Grade 3) which is not corrected prior to study enrolment. 18. 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 (eg octreotide long-acting), which cannot be interrupted for at least 6 weeks before the administration of Lutathera, unless the tumor uptake on target lesions observed by study-permitted somatostatin re

Design outcomes

Primary

Measure	Time frame
Main Objective: To demonstrate that Lutathera is superior to active comparator in delaying the time-to-first occurrence of progression or death (PFS) as first line treatment.;Secondary Objective: Key secondary objectives: -To demonstrate the superiority of Lutathera, compared to active comparator, in terms of objective response -To demonstrate the superiority of Lutathera, compared to active comparator, in terms of time to deterioration in selected QoL items/scales. Other Secondary Objectives: -To evaluate the efficacy of Lutathera, compared to active comparator, in keeping the disease under control -To evaluate the efficacy of Lutathera, compared to active comparator, in terms of duration of response -To evaluate the safety and tolerability of Lutathera -To evaluate the effect of Lutathera on survival ;Primary end point(s): Progression Free Survival (PFS): Time from randomization to the first line progression (centrally assessed according to RECIST 1.1) or death due to any cause. ;Timepoint(s) of evaluation of this end point: After 99 PFS events	—

Measure

Time frame

Main Objective: To demonstrate that Lutathera is superior to active comparator in delaying the time-to-first occurrence of progression or death (PFS) as first line treatment.;Secondary Objective: Key secondary objectives: -To demonstrate the superiority of Lutathera, compared to active comparator, in terms of objective response -To demonstrate the superiority of Lutathera, compared to active comparator, in terms of time to deterioration in selected QoL items/scales. Other Secondary Objectives: -To evaluate the efficacy of Lutathera, compared to active comparator, in keeping the disease under control -To evaluate the efficacy of Lutathera, compared to active comparator, in terms of duration of response -To evaluate the safety and tolerability of Lutathera -To evaluate the effect of Lutathera on survival ;Primary end point(s): Progression Free Survival (PFS): Time from randomization to the first line progression (centrally assessed according to RECIST 1.1) or death due to any cause. ;Timepoint(s) of evaluation of this end point: After 99 PFS events

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Secondary

Measure	Time frame
Secondary end point(s): -ORR: Rate of patients with best overall response of partial response (PR) or complete response (CR) (centrally assessed according to RECIST 1.1) -Time to decline (TTD) by 10 points from baseline in the following scores measured by the EORTC QLQ-G.I.NET21 questionnaire, EORTC QLQC30 questionnaire: global health status, diarrhea, fatigue and pain.;Timepoint(s) of evaluation of this end point: At the end of treatment phase or after discontinuation	—

Measure

Time frame

Secondary end point(s): -ORR: Rate of patients with best overall response of partial response (PR) or complete response (CR) (centrally assessed according to RECIST 1.1) -Time to decline (TTD) by 10 points from baseline in the following scores measured by the EORTC QLQ-G.I.NET21 questionnaire, EORTC QLQC30 questionnaire: global health status, diarrhea, fatigue and pain.;Timepoint(s) of evaluation of this end point: At the end of treatment phase or after discontinuation

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Countries

Canada, France, Germany, Italy, Korea, Republic of, Netherlands, Spain, United Kingdom, United States

Contacts

Public ContactRegulatory Affairs Team

Advanced Accelerator Applications International

Regulatory_Affairs@adacap.com+4122519 0700

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026