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 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 Pharmaceuticals
240 participants
May 30, 2025
INTERVENTIONAL
Conditions
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
Eligibility
Inclusion Criteria26
- 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 Criteria10
- 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.
Interventions
\[177Lu\]Lu-DOTA-TATE will be administered 4 times during treatment period with frequency of every 8 weeks (Q8W)
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.
Locations(62)
View Full Details on ClinicalTrials.gov
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NCT06784752