NCT02820857: BEVANEC

Assessment of the Efficacy of Bevacizumab in Combination With Folfiri as Second-line Treatment in Patients Suffering From an Advanced Inoperable Poorly Differentiated Neuroendocrine Carcinoma of an Unknown or Gastroentero-pancreatic Primary Cancer

Completed Phase 2 Last updated 3 September 2025

What this trial tests

Phase 2 trial testing Folfiri-bevacizumab in Neuroendocrine Carcinomas in 153 participants. Completed in 24 August 2024.

Timeline

4 September 2017

Primary endpoint
8 August 2022

24 August 2024

Quick facts

Lead sponsor	Hospices Civils de Lyon
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	153
Start date	4 September 2017
Primary completion	8 August 2022
Estimated completion	24 August 2024
Sites	26 locations across France

Drugs / interventions tested

• Folfiri-bevacizumab
• Folfiri (folfiri) — full drug profile →

Conditions studied

• Neuroendocrine Carcinomas — all drugs for Neuroendocrine Carcinomas →

Sponsor

Hospices Civils de Lyon — full company profile →

Who can join

18 and older, any sex, with Neuroendocrine Carcinomas. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Poorly differentiated neuroendocrine carcinomas (NEC) are a sub-group of aggressive neuroendocrine neoplasms (NEN). The most common primary sites are broncho-pulmonary and digestive. The gastroentero-pancreatic NECs (GEP-NEC) represent 7-21% of all of the NENs.

Recent data on the initial presentation of GEP-NEC have been reported in two retrospective studies and a French cohort study. No standard second-line treatment has been defined for NECs. Despite a very negative prognosis, these NECs have a certain amount of chemosensitivity, close to that of bronchial NECs. Multiple-drug therapies such as Folfiri, or Folfox, or single drug treatments such as temozolomide are the proposed options but with a low level of proof Bevacizumab associated with a cytotoxic chemotherapy has shown promising results in well differentiated neuroendocrine tumors (NET), known for being hypervascular. The efficacy of bevacizumab has also been suggested in patients with NEC, but never in the context of a phase II study. Its combination with Folfiri is efficient and well tolerated in metastatic colorectal cancer. The combination Folfiri-bevacizumab potentially represents an optimized treatment compared to chemotherapy with only Folfiri. No phase II or III studies have reported results for these patients, and no on-going phase II or III trial have been identified to date.

The main objective of this study is to show that, after the failure of a first-line chemotherapy using platinum-etoposide, the combination Folfiri-bevacizumab allows significant prolongation of overall survival in adult patients with GEP-NEC.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Bevacizumab plus FOLFIRI after failure of platinum-etoposide first-line chemotherapy in patients with advanced neuroendocrine carcinoma (PRODIGE 41-BEVANEC): a randomised, multicentre, non-comparative, open-label, phase 2 trial.
   Walter T, Lievre A, Coriat R, Malka D, et al · · 2023 · cited 34× · PMID 36739879 · DOI 10.1016/s1470-2045(23)00001-3
2. Expanding Therapeutic Opportunities for Extrapulmonary Neuroendocrine Carcinoma.
   Frizziero M, Kilgour E, Simpson KL, Rothwell DG, et al · · 2022 · cited 30× · PMID 35091446 · DOI 10.1158/1078-0432.ccr-21-3058
3. Second-line treatment in patients with advanced extra-pulmonary poorly differentiated neuroendocrine carcinoma: a systematic review and meta-analysis.
   McNamara MG, Frizziero M, Jacobs T, Lamarca A, et al · · 2020 · cited 30× · PMID 32426044 · DOI 10.1177/1758835920915299
4. Chemotherapy in NEN: still has a role?
   Espinosa-Olarte P, La Salvia A, Riesco-Martinez MC, Anton-Pascual B, et al · · 2021 · cited 25× · PMID 33843007 · DOI 10.1007/s11154-021-09638-0
5. Systemic Treatment of Gastroenteropancreatic Neuroendocrine Carcinoma.
   Mollazadegan K, Welin S, Crona J. · · 2021 · cited 21× · PMID 34110508 · DOI 10.1007/s11864-021-00866-9
6. Targeting Growth Factor Signaling Pathways in Pancreatic Cancer: Towards Inhibiting Chemoresistance.
   Xelwa N, Candy GP, Devar J, Omoshoro-Jones J, et al · · 2021 · cited 15× · PMID 34195085 · DOI 10.3389/fonc.2021.683788
7. 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.
   Walter T, Malka D, Hentic O, Lombard-Bohas C, et al · · 2018 · cited 15× · PMID 29258812 · DOI 10.1016/j.dld.2017.11.020
8. Randomised phase II trial of CAPTEM or FOLFIRI as SEcond-line therapy in NEuroendocrine CArcinomas and exploratory analysis of predictive role of PET/CT imaging and biological markers (SENECA trial): a study protocol.
   Bongiovanni A, Liverani C, Pusceddu S, Leo S, et al · · 2020 · cited 14× · PMID 32690499 · DOI 10.1136/bmjopen-2019-034393