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Clinical Trials/NCT06784752
NCT06784752
Recruiting
Phase 3

A Phase III Multi-center, Randomized, Open-label Study to Evaluate the Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Patients Newly Diagnosed With Grade 1 and Grade 2 (Ki-67 <10%) Advanced GEP-NET With High Disease Burden (NETTER-3)

Novartis Pharmaceuticals70 sites in 10 countries240 target enrollmentStarted: May 30, 2025Last updated:
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Interventions[177Lu]Lu-DOTA-TATEOctreotide LAR
DrugsOctreotide LAR

Overview

Phase
Phase 3
Status
Recruiting
Enrollment
240
Locations
70
Primary Endpoint
Progression Free Survival (PFS) centrally assessed by Blinded Independent Review Committee (BIRC)
OverviewStudy DesignEligibility CriteriaArms & InterventionsOutcomesInvestigatorsSitesRecords & IdentifiersSimilar Trials

Overview

Brief Summary

The purpose of the current study is to evaluate the efficacy and safety of [177Lu]Lu-DOTA-TATE plus octreotide long-acting release (LAR) versus octreotide LAR alone in newly diagnosed patients with somatostatin receptor positive (SSTR+), well differentiated Grade1 and Grade 2 (G1 and G2) (Ki-67 <10%) advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) with high disease burden

Detailed Description

The study consists of a screening phase, a treatment phase and a follow-up phase. This study compares treatment with [177Lu]Lu-DOTA-TATE plus octreotide LAR and octreotide LAR only.

Study Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel
Primary Purpose
Treatment
Masking
None

Eligibility Criteria

Ages
12 Years to 100 Years (Child, Adult, Older Adult)
Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • •Presence of metastasized or locally advanced, unresectable (curative intent), histologically proven, well differentiated Grade 1 or Grade 2 (Ki-67 \<10%) gastroenteropancreatic neuroendocrine tumor (GEP-NET) diagnosed within 6 months prior to screening.
  • •Participants with high disease burden in the Investigator's opinion. Following criteria should be used as the guiding principle for determining high disease burden:
  • •Primary tumor or a metastatic lesion \> 4 cm
  • •More than one tumor or metastatic lesions measuring \> 2 cm
  • •Elevated alkaline phosphatase \> 2.5 X upper limit of normal (ULN)
  • •Presence of bone metastasis
  • •Presence of peritoneal metastasis
  • •Symptoms due to tumor volume such as pain, fatigue, weight loss, anorexia etc.
  • •Symptoms due to hormone excess requiring active management
  • •Additionally, participants who, in the Investigator's opinion, have high disease burden due to their disease characteristics not specified above could also be considered eligible.

Exclusion Criteria

  • •Prior administration of a therapeutic radiopharmaceutical for GEP-NET at any time prior to randomization in the study.
  • •Any previous therapy with interferons, mTOR-inhibitors, chemotherapy or other systemic therapies except somatostatin analogues (SSAs) of GEP-NET. If as per Investigator's opinion a participant is candidate for such therapies, such participant must not be enrolled.
  • •Participant who received more than 4 cycles of prior SSAs (e.g., octreotide long-acting release) are not eligible. In addition, any participant receiving treatment with short-acting octreotide, which cannot be interrupted for 24 h before the administration of \[177Lu\]Lu-DOTA-TATE, or any participant receiving treatment with SSAs, which cannot be interrupted for at least 4 weeks before the administration of \[177Lu\]Lu-DOTA-TATE.
  • •Documented RECIST v1.1 progression during previous SSA treatments for the current GEP-NET at any time prior to randomization.
  • •Any previous radioembolization, chemoembolization and radiofrequency ablation for GEP-NET.
  • •Any major surgery within 12 weeks prior to randomization in the study.
  • •Known brain metastases.
  • •Participant with known intolerance to CT scans with intravenous (i.v.) contrast due to allergic reaction or renal insufficiency. If such a participant can be imaged with MRI, then the participant would not be excluded.
  • •Hypersensitivity to any somatostatin analogues, to the Investigational Medicinal Products (IMPs) active substance or to any of the excipients.
  • •Active severe urinary incontinence, severe voiding dysfunction, or urinary obstruction requiring an indwelling/condom catheter that, in the judgment of the Investigator, could prevent adhering to radiation safety instructions.

Arms & Interventions

[177Lu]Lu-DOTA-TATE + Octreotide LAR

Experimental

Participants in this arm will receive [177Lu]Lu-DOTA-TATE plus Octreotide long-acting release (LAR).

Intervention: [177Lu]Lu-DOTA-TATE (Radiation)

[177Lu]Lu-DOTA-TATE + Octreotide LAR

Experimental

Participants in this arm will receive [177Lu]Lu-DOTA-TATE plus Octreotide long-acting release (LAR).

Intervention: Octreotide LAR (Drug)

Octreotide LAR

Active Comparator

Participants in this arm will receive Octreotide LAR only.

Intervention: Octreotide LAR (Drug)

Outcomes

Primary Outcomes

Progression Free Survival (PFS) centrally assessed by Blinded Independent Review Committee (BIRC)

Time Frame: After observing approximately 88 PFS events as per BIRC assessments, expected after approximately 33 months from study start

PFS is defined as the time from randomization to the first occurrence of progression (centrally assessed by Blinded Independent Review Committee (BIRC) according to RECIST v1.1) or death due to any cause.

Secondary Outcomes

  • Time to Deterioration (TDD) (Key Secondary)(After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start)
  • Progression Free Survival (PFS)(After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start)
  • Absolute change from baseline in EORTC QLQ-G.I.NET21 domain(After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start)
  • Objective Response Rate (ORR)(After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start)
  • Disease Control Rate (DCR)(After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start)
  • Duration of Response (DOR)(After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start)
  • Overall Survival (OS)(Until 60 month from randomization)
  • Time to Deterioration (TDD)(At the time of primary PFS analysis after observing approximately 88 PFS events per BIRC assessment)
  • Absolute change from baseline in the EQ-5D-5L index at each time point(After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start)
  • Absolute change from baseline in EORTC QLQ-C30 domain(After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start.)
  • Dosimetry(After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start)
  • Pharmacokinetic (PK) parameter: Area Under Curve (AUC) from [177Lu]Lu-DOTA-TATE blood radioactivity data(After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start)
  • PK parameter: Clearance from [177Lu]Lu-DOTA-TATE blood radioactivity data(After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start)
  • PK parameter: Distribution volume (Vz) from [177Lu]Lu-DOTA-TATE blood radioactivity data(After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start)
  • PK parameter: half-life (T1/2) from [177Lu]Lu-DOTA-TATE blood radioactivity data(After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start)

Investigators

Sponsor Class
Industry
Responsible Party
Sponsor

Study Sites (70)

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