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

NCT06784752 · Novartis
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Official title
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)
About this study
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.
Eligibility criteria
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: * 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.
Study design
Enrollment target: 240 participants
Allocation: randomized
Masking: none
Age groups: child, adult, older_adult
Timeline
Starts: 2025-05-30
Estimated completion: 2034-01-23
Last updated: 2026-04-30
Interventions
Radiation: [177Lu]Lu-DOTA-TATEDrug: Octreotide LAR
Primary outcomes
  • Progression Free Survival (PFS) centrally assessed by Blinded Independent Review Committee (BIRC) (After observing approximately 88 PFS events as per BIRC assessments, expected after approximately 33 months from study start)
Sponsor
Novartis Pharmaceuticals · industry
Contacts & investigators
ContactNovartis Pharmaceuticals · contact · novartis.email@novartis.com · 1-888-669-6682
ContactNovartis Pharmaceuticals · contact · +41613241111
InvestigatorNovartis Pharmaceuticals · study_director, Novartis Pharmaceuticals
All locations (65)
Mayo Clinic ArizonaRecruiting
Scottsdale, Arizona, United States
Highlands Oncology GroupRecruiting
Fayetteville, Arkansas, United States
Rocky Mountain Cancer CentersRecruiting
Denver, Colorado, United States
Hartford HospitalRecruiting
Hartford, Connecticut, United States
Yale New Haven HospitalRecruiting
New Haven, Connecticut, United States
Mayo Clinic JacksonvilleRecruiting
Jacksonville, Florida, United States
Winship Cancer InstituteRecruiting
Atlanta, Georgia, United States
St Elizabeth HealthcareRecruiting
Edgewood, Kentucky, United States
LSU Medical CenterRecruiting
New Orleans, Louisiana, United States
Henry Ford HospitalRecruiting
Detroit, Michigan, United States
Mount Sinai Medical CenterRecruiting
New York, New York, United States
Piedmont HealthcareRecruiting
Winston-Salem, North Carolina, United States
Tennessee OncologyRecruiting
Nashville, Tennessee, United States
TxO Austin MidtownActive Not Recruiting
Austin, Texas, United States
Texas OncologyRecruiting
Dallas, Texas, United States
Virginia Cancer SpecialistsRecruiting
Fairfax, Virginia, United States
Virginia Oncology AssociatesRecruiting
Norfolk, Virginia, United States
Blue Ridge Cancer CenterRecruiting
Wytheville, Virginia, United States
Northwest Medical SpecialtiesRecruiting
Tacoma, Washington, United States
Novartis Investigative SiteRecruiting
Edmonton, Alberta, Canada
Novartis Investigative SiteRecruiting
London, Ontario, Canada
Novartis Investigative SiteRecruiting
Toronto, Ontario, Canada
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Montreal, Quebec, Canada
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Beijing, China
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Beijing, China
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Beijing, China
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Shanghai, China
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Bron, France
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Clichy, France
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Montpellier, France
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Nantes, France
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Pessac, France
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Toulouse, France
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Erlangen, Germany
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Essen, Germany
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München, Germany
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Budapest, Hungary
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Szeged, Hungary
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Cona, FE, Italy
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Genova, GE, Italy
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Milan, MI, Italy
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Rozzano, MI, Italy
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Pisa, PI, Italy
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Roma, RM, Italy
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Roma, RM, Italy
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Milan, Italy
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Rotterdam, South Holland, Netherlands
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Utrecht, Netherlands
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Gdansk, Poland
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Gliwice, Poland
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Krakow, Poland
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Poznan, Poland
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Warsaw, Poland
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Warsaw, Poland
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Seoul, South Korea
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Seoul, South Korea
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Seoul, South Korea
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L'Hospitalet de Llobregat, Barcelona, Spain
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Oviedo, Principality of Asturias, Spain
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Barcelona, Spain
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Madrid, Spain
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Madrid, Spain
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Madrid, Spain
Novartis Investigative SiteRecruiting
Salamanca, Spain
Novartis Investigative SiteRecruiting
London, United Kingdom
Study to Evaluate the Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Patients With Grade 1 and Grade 2 Advanced GEP-NET · TrialPath