PRRT Versus PRRT Plus Chemotherapy in GEP NET (PReCedeNT Trial)

Summary

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.

Eligibility

Inclusion Criteria:

* 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
* Positive Ga-68-DOTANOC PET/CT, Krennings score \>/=3
* Positive FDG PET imaging, grade 3 or 4 uptake
* Locally advanced/inoperable disease or metastatic disease
* Karnofsky performance-status score of at least 60 or ECOG performance status \</= 2
* Life expectancy greater than 6 months

Exclusion Criteria:

* 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
* Total bilirubin level of more than 3 times the upper limit of the normal range
* Serum albumin level \< 3.0 g/dl
* Treatment with more than 30 mg of octreotide LAR within 4 weeks before randomisation.
* Peptide receptor radionuclide therapy at any time before randomisation
* Pregnancy and Lactation
* Patients with concurrent malignancies

Conditions4

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