Evaluating bevacizumab in combination with FOLFIRI after the failure of platinum-etoposide regimen in patients with advanced poorly differentiated neuroendocrine carcinoma: The PRODIGE 41-BEVANEC randomized phase II study

Dig Liver Dis. 2018 Feb;50(2):195-198. doi: 10.1016/j.dld.2017.11.020. Epub 2017 Dec 6.

Abstract

Introduction: Patients with gastroenteropancreatic (GEP), metastatic or locally advanced, non-resectable, grade 3 poorly-differentiated neuroendocrine carcinoma (NEC) are treated with cisplatin (or carboplatin)-etoposide in first-line palliative chemotherapy (CT1). However, nearly all patients will develop resistance and there is no standard second-line treatment.

Aim: PRODIGE 41-BEVANEC is an academic randomized, phase II study designed to evaluate the efficacy of bevacizumab in combination with FOLFIRI after failure of CT1 in unknown primary NEC and GEP-NEC.

Materials and methods: The main eligibility criteria are age ≥18 years, metastatic (synchronous or metachronous) or locally advanced, non-resectable, grade 3 GEP-NEC, and documented progressive disease during or after CT1 therapy.

Results: A total of 124 patients will be randomly assigned (1:1) to receive either 5 mg/kg bevacizumab with FOLFIRI, or FOLFIRI alone, every 14 days until disease progression or unacceptable toxicity. The hypothesis is to demonstrate a 6-month overall survival for at least 50% of the patients in bevacizumab arm versus 35% in the control arm (FOLFIRI alone). Secondary endpoints are objective response, response duration, progression-free survival, toxicity, and biochemical response.

Conclusion: The study is currently opened in France (NCT02820857). The first patient was randomized on September 6, 2017.

Keywords: Bevacizumab; Clinical trial; FOLFIRI; Gastroenteropancreatic; Neuroendocrine carcinoma.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage
  • Bevacizumab / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives*
  • Camptothecin / therapeutic use
  • Carcinoma, Neuroendocrine / drug therapy*
  • Carcinoma, Neuroendocrine / mortality
  • Drug Administration Schedule
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / therapeutic use
  • France
  • Humans
  • Intestinal Neoplasms / drug therapy*
  • Intestinal Neoplasms / mortality
  • Leucovorin / administration & dosage
  • Leucovorin / therapeutic use
  • Male
  • Neuroendocrine Tumors / drug therapy*
  • Neuroendocrine Tumors / mortality
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / mortality
  • Research Design
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / mortality
  • Survival Analysis
  • Treatment Outcome

Substances

  • Bevacizumab
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • Gastro-enteropancreatic neuroendocrine tumor
  • IFL protocol