study to evaluate the efficacy and safety of [177lu]lu-dota-tate in patients with grade 1 and grade 2 advanced gep-net

Conditions: Somatostatin Receptor Positive (SSTR+); Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET)

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

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.

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