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AzTrials

Neuroendocrine CarcinomasPhase 2BEVANECNCT02820857

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

A Phase 2 study testing Folfiri-bevacizumab and Folfiri in people with Neuroendocrine Carcinomas, run by Hospices Civils de Lyon at 26 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neuroendocrine Carcinomas
What is being tested?
Folfiri-bevacizumab and Folfiri
Could I receive a placebo?
No, everyone receives an active treatment
How many people
153 participants
Where
26 sitesFrance
Study dates
4 Sep 2017to 24 Aug 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Man or woman aged ≥ 18 years old,
  • Poorly differentiated neuroendocrine carcinoma (NEC) from a gastrointestinal tract (from esophagus to anal canal) and biliopancreatic primary or an unknown primary cancer, locally advanced and/or metastatic,
  • Centralized review of the diagnostic by a consulting pathologist specializing in NET (TENPATH network),
  • Recommendation of a second-line chemotherapy after progression, documented using the RECIST criteria v.1.1, and after a first-line chemotherapy treatment by cisplatin (or carboplatin) + etoposide or in the event of progression in the 6 months following the discontinuation of this first-line treatment,
  • Recommendation of a second-line chemotherapy for the refractory patient or contraindicated for platinum-etoposide chemotherapy
  • Patients presenting at least one measurable target lesion according to the RECIST criteria v.1.1, in an area not previously irradiated,
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  • General condition ≤ 2 (WHO),
  • Patient of child bearing age accepting to use an effective contraception during treatment and until 6 months after the last administration,
  • Patient who signed the informed consent form.

Who cannot join

  • Relating to the tumor, the patient, and previous treatment:
  • Well differentiated neuroendocrine tumor
  • Mixed tumor, except if the NEC component is > 70%, the patient is eligible,
  • First-line chemotherapy other than cisplatin (or carboplatin) and etoposide,
  • All malignant disease in the three years before randomization, with the exception of basal cell carcinoma or in situ cancer treated for curative purposes,
  • A pregnant or breastfeeding woman,
Show all 26Show fewer
  • Lack of efficient contraception (for men or women of reproductive age),
  • All medical, geographical, social, and psychological conditions or a legal situation that will not allow the patient to finish the study or sign an informed consent form,
  • Relating to the chemotherapy (Folfiri):
  • Any of the following uncontrolled progressive diseases in the 6 months before randomization: liver failure, renal insufficiency, respiratory distress, congestive heart failure (NYHA III-IV), unstable angina, myocardial infarction, significant arrhythmia,
  • Known deficiency in dihydropyrimidine dehydrogenase,
  • Known Gilbert's syndrome,
  • Total bilirubin level >1.5x the upper limit of normal (ULN); AST (Aspartate transaminase) and/or ALT (Alanine transaminase) >5x ULN; TP <50%;
  • Neutrophils <1.5x109/l, platelets <100x109/l, hemoglobin <9 g/dl,
  • Chronic uncontrolled diarrhea, unresolved intestinal occlusion or subocclusion,
  • History of anaphylactic reaction or known intolerance to atropine (sulfate) or to loperamide or to antiemetics administered in association with Folfiri,
  • All treatment with concomitant anticonvulsive agents, CYP3A4 inducers (phenytoin, phenobarbital, carbamazepine), discontinued for at least 7 days,
  • Relating to bevacizumab:
  • Uncontrolled brain metastases (by local treatment),
  • All uncontrolled progressive disease within 1 month prior to randomization: grade 3-4 gastrointestinal bleeding (peptic ulcer, erosive esophagitis or gastritis), infectious disease or intestinal inflammation, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event,
  • Uncontrolled high blood pressure defined as a systolic blood pressure >140 mmHg or diastolic pressure >90 mmHg,
  • Patients receiving anticoagulant treatment with an unstable dose of a vitamin K antagonist treatment, and/or having an abnormal INR (>3) in the four weeks before the randomization,
  • Verified proteinuria above or equal to 1g/24 hours measured from 24 hours of urine if the urinary protein dipstick control is above or equal to 2+,
  • Creatinine clearance (MDRD) <50 ml/min.
  • Hypersensitivity to the active substance or to any of the excipients.
  • Hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies.

Trial locations and contacts

26 sites in 1 country.

26 sites in 1 country

France26 sites

  • Service d'Hépato-Gastroenterologie et Oncologie Digestive, Hôpital Sud, CHU d'Amiens

    Amiens, 80054

  • Service d'Hépatogastroentérologie, CHU d'Angers

    Angers, 49933

  • Service d'Oncologie et Radiothérapie, Institut Sainte Catherine

    Avignon, 84918

  • Service de Gastroentérologie et Oncologie Digestive, Hôpital Avicenne

    Bobigny, 93000

  • Service de Gastroentérologie et Pancréatologie, Hôpital Beaujon, APHP

    Clichy, 92118

  • Service de Gastroentérologie, CHU Henri Mondor

    Créteil, 94000

  • Service d'Hépato-Gastroentérologie et Oncologie Digestive, CHU de Dijon

    Dijon, 21000

  • Service d'Hépatogastroentéologie, Hôpital Michallon, CHU de Grenoble

    Grenoble, 38043

  • Département de Cancérologie Urologique et Digestive, Centre Oscar Lambret

    Lille, 59020

  • Département de cancérologie médicale - Groupe des tumeurs endocrines, Centre Léon Bérard

    Lyon, 69008

  • Service d'Oncologie Médicale - Hôpital Edouard Herriot - Hospices Civils de Lyon

    Lyon, 69437

  • Département d'Oncologie Médicale, Institut Paoli Calmettes

    Marseille, 13009

  • Service d'Hépato-Gastroentérologie et d'Oncologie Digestive, Hôpital de la Timone, APHM

    Marseille, 13365

  • Service d'Oncologie Médicale, Hôpital Saint Eloi, CHU de Montpellier

    Montpellier, 34298

  • Service d'Hépatogastroentérologie, CHR d'Orléans

    Orléans, 45067

  • Département d'Oncologie Médicale, Hôpital Saint-Antoine

    Paris, 75012

  • Service de Gastroentérologie, Hôpital Cochin, APHP

    Paris, 75014

  • Service d'Hépato-Gastroenterologie et Oncologie Digestive, Hôpital Européen Georges Pompidou, APHP

    Paris, 75015

  • Service d'Hépato-Gastroentérologie et d'Oncologie Digestive, Hôpital Haut Lévêque, CHU Bordeaux

    Pessac, 33604

  • Pôle Régional de Cancérologie, CHU de Poitiers

    Poitiers, 86021

  • Service d'Hépato-Gastroentérologie et Cancérologie, Hôpital Robert Debré, CHU de Reims

    Reims, 51100

  • Service d'Hépatogastroentérologie, Hôpital Pontchaillou, CHU de Rennes

    Rennes, 35000

  • Service de Gastroentérologie, CHU de Rouen

    Rouen, 76031

  • Service de Gastro-Entérologie, Hôpital Nord, CHU de ST-Etienne

    Saint-Priest-en-Jarez, 42270

  • Service d'Oncologie Médicale, Hôpital Civil, CHU de Strasbourg

    Strasbourg, 67200

  • Service d'Oncologie Endocrinienne, Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

About this study

Official title: Assessment of the Efficacy of Bevacizumab in Combination With Folfiri as Second-line Treatment After the Failure of the Cisplatin (or Carboplatin)-Etoposide Combination in Patients Suffering From an Advanced Inoperable Poorly Differentiated Neuroendocrine Carcinoma of an Unknown or Gastroentero-pancreatic Primary Cancer. A Phase 2 Non-comparative Randomized Study

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.

Being tested
Folfiri-bevacizumab, Folfiri
Keywords
Gastroentero-pancreatic neuroendocrine carcinomas, Second-line treatment, Bevacizumab, Folfiri
Medical subject headings
Carcinoma, Neuroendocrine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Folfiri-bevacizumabDrug

    Patient treated with a combination Folfiri-bevacizumab. Treatment every 2 weeks (D1 = D15)

  • FolfiriDrug

    Patient treated with Folfiri only. Treatment every 2 weeks (D1 = D15)

Study groups in NCT02820857
Study groupRoleWhat they receive
Folfiri-bevacizumabExperimentalPatient treated with a combination Folfiri-bevacizumab. Treatment every 2 weeks (D1 = D15)
Receives: Drug: Folfiri-bevacizumab
FolfiriActive comparatorPatient treated with Folfiri only. Treatment every 2 weeks (D1 = D15)
Receives: Drug: Folfiri

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of patients alive

    The primary endpoint is the proportion of patients alive 6 months after treatment

    Measured: 6 months after treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jul 2016 (estimated)
  2. Study start4 Sep 2017
  3. Primary completion8 Aug 2022
  4. Study completion24 Aug 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
153 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02820857
Sponsor's protocol ID
69HCL14_0442
Other IDs
2016-001305-16, 2016
Acronym
BEVANEC
Status last verified
Aug 2025
First submitted
29 Jun 2016
Last updated
3 Sep 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Walter T, Lievre A, Coriat R, Malka D, Elhajbi F, Di Fiore F, Hentic O, Smith D, Hautefeuille V, Roquin G, Perrier M, Dahan L, Granger V, Sobhani I, Mineur L, Niccoli P, Assenat E, Scoazec JY, Le Malicot K, Lepage C, Lombard-Bohas C. 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. Lancet Oncol. 2023 Mar;24(3):297-306. doi: 10.1016/S1470-2045(23)00001-3. Epub 2023 Feb 2.

    PubMed 36739879

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Folfiri-bevacizumab and Folfiri in people with Neuroendocrine Carcinomas, run by Hospices Civils de Lyon at 26 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of patients alive (time frame: 6 months after treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02820857, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2025.

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