Neuroendocrine tumours (NETs), better defined as neoplasms (NENs), are a heterogeneous group of neoplasms that range from well-differentiated tumours to more aggressive carcinomas. Peptide receptor radionuclide therapy (PRRT) with Lutetium-177 DOTATATE is the established standard of care for patients with well-differentiated metastatic or locally advanced GEP-NETs. It has demonstrated a significant improvement in outcomes compared to Octreotide LAR, both as a first-line and second-line treatment approach, following the results of NETTER-1 and NETTER-2 trials, respectively. ENETS guidelines recommend the use of Ga-68 labeled DOTANOC/TOC/TATAE imaging only for WHO Grade 1 NET whereas FDG PET is the preferred modality for WHO Grade 3 NEN and NEC. For Grade 2 tumors (Mib index ranging from 3-20%), there are no strong recommendations for the addition of FDG PETCT in existing diagnostic algorithm. FDG PET positivity has been shown to be an independent predictor of shorter progression-free and overall survival in NET patients undergoing peptide receptor radionuclide therapy (PRRT). (8) Consequently, it is imperative to address FDG-avid tumors by integrating PRRT and chemotherapy. There are no strong recommendations for the grade wise management of GEP-NETs particularly grade 2 \& 3. Although recently published NETTER 2 trial substantiated the role of PRRT as a first line treatment for advanced grade GEP-NETs, still there is lack of evidence supporting the addition of chemotherapy in management of GEP-NETs. Given the absence of a prospective study to establish this treatment regimen, we designed a Phase 3 Randomized Controlled Trial to evaluate the combination of PRRT and CAPE-TEM-based chemotherapy in patients with FDG-positive metastatic well-differentiated NETs.
Male or female, age greater than 18 years
Histopathological diagnosis of GEP-NET, necessarily satisfying all the the criteria below
Well differentiated G2 (Ki67 : ≥3-20%) OR G3 (ki67- greater than 20-55%), OR
Well-differentiated G1 (<3%) with disease progression in last 6 months
Serum creatinine level of more than 1.6 mg/dl or a creatinine clearance of less than 50 ml/min
Hemoglobin level of less than 8.0 g per deciliter
Red blood cell count noty less than 300,000/cubic millimeter White cell count of less than 2000 per cubic millimeter
Platelet count of less than 75,000 per cubic millimetre
Parallel
Peptide Receptor Radionuclide Therapy with Lu177 DOTATATE
RadiationRadionuclide Therapy
Capecitabine plus temozolamide
DrugChemotherapy
Progression free survival
Progression-free survival (PFS) will be defined as the time from enrolment to the time of disease progression or death, or to the date of last tumor assessment (until 36 months from last day of completion of treatment) without any such event (censored observation).
Overall survival
The duration of overall survival (OS) will be determined by measuring the time interval from enrolment to the date of death or last observation (censored).
Quality of Life parameters
QOL analysis will be conducted using the following tools (with appropriate language translations) EORTC QLQ-30 EORTC G.I.NET-21
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