CClinicalTrials.gg
RecruitingNCT06784752NETTER-3Updated Sep 11, 2026

Study to Evaluate the Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Patients With Grade 1 and Grade 2 Advanced GEP-NET

A Phase 3 interventional study of [177Lu]Lu-DOTA-TATE and Octreotide LAR in Somatostatin Receptor Positive (SSTR+) and Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET), sponsored by Novartis Pharmaceuticals. Recruiting at 67 sites in 12 countries. Open to participants aged 12 Years to 100 Years. Per ClinicalTrials.gov, last updated 2026-09-11.

Sponsored by Novartis Pharmaceuticals · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
240
Allocation
Randomized
Ages
12 Years to 100 Years
Sex
All
01

Study 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

Read the 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.

02

Conditions studied

  • Somatostatin Receptor Positive (SSTR+)
  • Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET)

Keywords

  • SSTR+
  • GEP-NET
  • Ki-67 <10%
  • AAA601
  • [177Lu]Lu-DOTA-TATE
  • newly diagnosed
  • well differentiated
  • advanced GEP-NETs
  • high disease burden
  • NETTER-3
  • Grade 1
  • Grade 2
  • Tumor-targeted radioligand therapy
  • RLT
  • octreotide LAR
  • Gastroenteropancreatice Neuroendocrine Tumor
  • PFS
  • Quality of life (QOL)/PRO
  • QoL
  • neuroendocrine tumor(s)
  • Lutathera
  • Lutetium dotatate
  • Lutetium oxodotreotide
03

Who can participate

Ages eligible
12 Years to 100 Years
Sexes eligible
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.
  • Participants ≥ 12 years of age.
  • RLI somatostatin receptor (SSTR) uptake on all target lesions (defined by RECIST v1.1 criteria) at least as high as normal liver uptake assessed within 3 months prior to randomization. Any of the RLI modalities as available (some examples are listed below) can be used as per local practice:

    • [68Ga]Ga-DOTA-TOC PET/CT or PET/MRI
    • [68Ga]Ga-DOTA-TATE PET/CT or PET/MRI
    • [64Cu]Cu-DOTA-TATE PET/CT or PET/MRI
    • Somatostatin receptor scintigraphy (SRS) (planar and/or SPECT/CT) with [111In]In-pentetreotide
    • SRS (planar and/or SPECT/CT) with [99mTc]Tc-octreotide.
  • Adequate bone marrow and organ function as defined by the following laboratory values prior to receiving the first study treatment:

    • White blood cell (WBC) count ≥ 2 x 109/L
    • Platelet count ≥ 75 x 109/L
    • Hemoglobin (Hb) ≥ 8 g/dL
    • Creatinine clearance > 40 mL/min calculated by the Cockcroft Gault method
    • Total bilirubin ≤ 3 x ULN
    • Potassium within normal limits. Potassium level of up to 6.0 millimoles per liter (mmol/L) is acceptable at study entry if associated with creatinine clearance within normal limits calculated using Cockcroft-Gault formula. Mild decrease (grade 1) below lower limit of normal (LLN) is acceptable at study entry if considered not clinically significant by Investigator.
  • ECOG performance status 0-1.
  • Presence of at least 1 measurable site of disease.

Exclusion criteria

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.

Other protocol-defined Inclusion/Exclusion criteria may apply.

04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
240 participants (estimated)

Study arms

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

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

    Radiation: [177Lu]Lu-DOTA-TATE · Drug: Octreotide LAR

  • Active comparator
    Octreotide LAR

    Participants in this arm will receive Octreotide LAR only.

    Drug: Octreotide LAR

Interventions

  • Radiation[177Lu]Lu-DOTA-TATE

    \[177Lu\]Lu-DOTA-TATE will be administered 4 times during treatment period with frequency of every 8 weeks (Q8W)

  • DrugOctreotide LAR

    Octreotide LAR will be administered Q8W when co-administered with \[177Lu\]Lu-DOTA-TATE in the investigational arm followed by Q4W. In the control arm Octreotide LAR will be administered Q4W.

    Also known as: SOM230

05

What researchers measure

Primary outcomes

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

    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.

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

Secondary outcomes

  1. Time to Deterioration (TDD) (Key Secondary)

    Time to deterioration is defined as the time from randomization to the first occurrence of a deterioration compared to the baseline scores or death from any cause for each of the following domains (tested separately) of EORTC QLQ-GI.NET21 \[gastrointestinal scale (GI scale)\] and EORTC QLQ-C30 questionnaires (fatigue, diarrhea, and global health scale).

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

  2. Progression Free Survival (PFS)

    PFS is defined as the time from randomization to the first occurrence of progression (Investigator assessed according to RECIST v1.1) or death due to any cause.

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

  3. Objective Response Rate (ORR)

    ORR: Rate of participants with best overall response (BOR) of partial response (PR) or complete response (CR) as per RECIST v1.1 (both Investigator and centrally assessed by BIRC).

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

  4. Disease Control Rate (DCR)

    DCR: Rate of participants with BOR of PR, CR or stable disease (SD) as per RECIST v1.1 (both Investigator and centrally assessed by BIRC).

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

  5. Duration of Response (DOR)

    DOR: The time from initially meeting the criteria for response (CR or PR) until the time of progression according to RECIST v1.1 or death due to underlying disease only.

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

  6. Overall Survival (OS)

    OS: Time from the randomization date until the date of death due to any cause.

    Time frame: Until 60 month from randomization

  7. Time to Deterioration (TDD)

    TTD is the time from randomization to the first occurrence of a deterioration compared to the baseline scores or death from any cause for EORTC QLQ-G.I.NET21 and EORTC QLQ-C30 domains not included among key secondary endpoints.

    Time frame: At the time of primary PFS analysis after observing approximately 88 PFS events per BIRC assessment

  8. Absolute change from baseline in EORTC QLQ-G.I.NET21 domain

    Quality of Life assessed by EORTC QLQ-G.I.NET21 (excluding GI scale) (domains not included as key secondary objectives)

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

  9. Absolute change from baseline in the EQ-5D-5L index at each time point

    Quality of Life assessed by EQ-5D-5L

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

  10. Absolute change from baseline in EORTC QLQ-C30 domain

    Quality of Life assessed by EORTC QLQ-C30 (domains not included as key secondary objectives)

    Time frame: After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start.

  11. Dosimetry

    Absorbed radiation dose in selected organs, tumor lesions and total body

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

  12. Pharmacokinetic (PK) parameter: Area Under Curve (AUC) from [177Lu]Lu-DOTA-TATE blood radioactivity data

    The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1). The AUC from time zero to infinity (mass x time x volume-1)

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

  13. PK parameter: Clearance from [177Lu]Lu-DOTA-TATE blood radioactivity data

    Clearance is the total body clearance of drug from the plasma or blood (volume x time-1).

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

  14. PK parameter: Distribution volume (Vz) from [177Lu]Lu-DOTA-TATE blood radioactivity data

    The apparent volume of distribution during terminal phase (associated with λz) (volume)

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

  15. PK parameter: half-life (T1/2) from [177Lu]Lu-DOTA-TATE blood radioactivity data

    The elimination half-life associated with the terminal slope (λz) of a semi logarithmic concentration-time curve (time). Use qualifier for other half-lives

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

06

Study locations

66 of 67 sites recruiting
  • Mayo Clinic Arizona
    Scottsdale, Arizona 85259, United States
    Recruiting
  • Highlands Oncology Group
    Fayetteville, Arkansas 72703, United States
    • Tina Patrick · Contact · tpatrick@hogonc.com · +1 479 878 7098
    • Joseph Thaddeus Beck · Principal investigator
    Recruiting
  • Rocky Mountain Cancer Centers
    Denver, Colorado 80218, United States
    Recruiting
  • Hartford Hospital
    Hartford, Connecticut 06102, United States
    Recruiting
  • Yale New Haven Hospital
    New Haven, Connecticut 06520, United States
    Recruiting
  • Mayo Clinic Jacksonville
    Jacksonville, Florida 32224, United States
    Recruiting
  • AdventHealth
    Orlando, Florida 32804, United States
    Recruiting
  • Piedmont Healthcare
    Atlanta, Georgia 30318, United States
    Recruiting
  • Winship Cancer Institute
    Atlanta, Georgia 30322, United States
    • Bridget Fielder · Contact · bfielde@emory.edu · 404-686-8210
    • Amol Takalkar · Principal investigator
    Recruiting
  • St Elizabeth Healthcare
    Edgewood, Kentucky 41017, United States
    Recruiting
  • LSU Medical Center
    New Orleans, Louisiana 70112, United States
    • Dominique Breaux · Contact · dkell3@lsuhsc.edu
    • Mary Maluccio · Principal investigator
    Recruiting
  • Henry Ford Hospital
    Detroit, Michigan 48202-2689, United States
    • Christina Vu · Contact · cvu1@hfhs.org · 313-876-1850
    • Philip A Philip · Principal investigator
    Recruiting
  • Mount Sinai Medical Center
    New York, New York 10029-6574, United States
    Recruiting
  • Tennessee Oncology
    Nashville, Tennessee 37203, United States
    Recruiting
  • TxO Austin Midtown
    Austin, Texas 78705, United States
    Active, not recruiting
  • Texas Oncology
    Dallas, Texas 75251, United States
    Recruiting
  • Virginia Cancer Specialists
    Fairfax, Virginia 22031, United States
    Recruiting
  • Virginia Oncology Associates
    Norfolk, Virginia 23502, United States
    Recruiting
  • Blue Ridge Cancer Center
    Wytheville, Virginia 24382, United States
    Recruiting
  • Northwest Medical Specialties
    Tacoma, Washington 98405, United States
    • Patricia Walsh · Contact · pwalsh@nwmsonline.com · 253-841-4296
    • Mohammed N Kanaan · Principal investigator
    Recruiting
  • Novartis Investigative Site
    Edmonton, Alberta T6G 1Z2, Canada
    Recruiting
  • Novartis Investigative Site
    London, Ontario N6A 5W9, Canada
    Recruiting
  • Novartis Investigative Site
    Toronto, Ontario M4N 3M5, Canada
    Recruiting
  • Novartis Investigative Site
    Montreal, Quebec H3T 1E2, Canada
    Recruiting
  • Novartis Investigative Site
    Beijing, 100036, China
    Recruiting
  • Novartis Investigative Site
    Beijing, 100730, China
    Recruiting
  • Novartis Investigative Site
    Beijing, 102200, China
    Recruiting
  • Novartis Investigative Site
    Shanghai, 200032, China
    Recruiting
  • Novartis Investigative Site
    Bron, 69677, France
    Recruiting
  • Novartis Investigative Site
    Clichy, 92110, France
    Recruiting
  • Novartis Investigative Site
    Montpellier, 34298, France
    Recruiting
  • Novartis Investigative Site
    Nantes, 44093, France
    Recruiting
  • Novartis Investigative Site
    Pessac, 33604, France
    Recruiting
  • Novartis Investigative Site
    Toulouse, 31059, France
    Recruiting
  • Novartis Investigative Site
    Erlangen, 91054, Germany
    Recruiting
  • Novartis Investigative Site
    Essen, 45147, Germany
    Recruiting
  • Novartis Investigative Site
    München, 80377, Germany
    Recruiting
  • Novartis Investigative Site
    Budapest, 1083, Hungary
    Recruiting
  • Novartis Investigative Site
    Szeged, 6725, Hungary
    Recruiting
  • Novartis Investigative Site
    Cona, FE 44124, Italy
    Recruiting
  • Novartis Investigative Site
    Genova, GE 16132, Italy
    Recruiting
  • Novartis Investigative Site
    Milan, MI 20133, Italy
    Recruiting
  • Novartis Investigative Site
    Milan, MI 20141, Italy
    Recruiting
  • Novartis Investigative Site
    Rozzano, MI 20089, Italy
    Recruiting
  • Novartis Investigative Site
    Pisa, PI 56126, Italy
    Recruiting
  • Novartis Investigative Site
    Roma, RM 00168, Italy
    Recruiting
  • Novartis Investigative Site
    Roma, RM 00189, Italy
    Recruiting
  • Novartis Investigative Site
    Rotterdam, South Holland 3015 GD, Netherlands
    Recruiting
  • Novartis Investigative Site
    Utrecht, 3584 CX, Netherlands
    Recruiting
  • Novartis Investigative Site
    Gdansk, 80-214, Poland
    Recruiting
  • Novartis Investigative Site
    Gliwice, 44-101, Poland
    Recruiting
  • Novartis Investigative Site
    Krakow, 30-688, Poland
    Recruiting
  • Novartis Investigative Site
    Poznan, 60-355, Poland
    Recruiting
  • Novartis Investigative Site
    Warsaw, 02-351, Poland
    Recruiting
  • Novartis Investigative Site
    Warsaw, 04-141, Poland
    Recruiting
  • Novartis Investigative Site
    Seoul, 03080, South Korea
    Recruiting
  • Novartis Investigative Site
    Seoul, 03722, South Korea
    Recruiting
  • Novartis Investigative Site
    Seoul, 05505, South Korea
    Recruiting
  • Novartis Investigative Site
    L'Hospitalet de Llobregat, Barcelona 08907, Spain
    Recruiting
  • Novartis Investigative Site
    Oviedo, Principality of Asturias 33011, Spain
    Recruiting
  • Novartis Investigative Site
    Barcelona, 08035, Spain
    Recruiting
  • Novartis Investigative Site
    Madrid, 28034, Spain
    Recruiting
  • Novartis Investigative Site
    Madrid, 28040, Spain
    Recruiting
  • Novartis Investigative Site
    Madrid, 28041, Spain
    Recruiting
  • Novartis Investigative Site
    Salamanca, 37007, Spain
    Recruiting
  • Novartis Investigative Site
    Glasgow, G12 0YN, United Kingdom
    Recruiting
  • Novartis Investigative Site
    London, SE5 9RS, United Kingdom
    Recruiting
07

References and documents

Individual participant data

Plan to share: Yes — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT06784752
Lead sponsor
Novartis Pharmaceuticals
Responsible party
Sponsor
First posted
Jan 20, 2025
Start date
May 30, 2025
Primary completion
Dec 8, 2028 (estimated)
Completion
Jan 23, 2034 (estimated)
Last update
Sep 11, 2026

Study contacts

Novartis Pharmaceuticals
Contact
novartis.email@novartis.com
1-888-669-6682
Novartis Pharmaceuticals
Contact
+41613241111
Novartis Pharmaceuticals
study director · Novartis Pharmaceuticals

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
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