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Neuroendocrine TumorsMGMT-NETNCT03217097

MGMT-NET: O6-methylguanine-DNA Methyltransferase (MGMT) Status in Neuroendocrine Tumors: Predictive Factor of Response to Alkylating Agents

A study testing Oxaliplatin-based chemotherapy and Alkylating-based chemotherapy in people with Neuroendocrine Tumors, run by Hospices Civils de Lyon at 19 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

Neuroendocrine tumors (NET) are rare but their incidence is growing. Alkylating agents (ALKY) are one of the main systemic treatments used, at least for advanced duodeno-pancreatic NETs, with a response rate of 30 to 40% and a median progression-free survival of 4 to 18 months. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neuroendocrine Tumors
What is being tested?
Oxaliplatin-based chemotherapy and Alkylating-based chemotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
116 participants
Where
19 sitesFrance
Study dates
16 Oct 2018to 25 Apr 2022
Phase
Interventional
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

  • Age greater than or equal to 18 years;
  • Patient presenting well-differentiated advanced grade 1-3 (locally/metastatic) duodeno-pancreatic or thoracic (lung or thymus) or unknown primitive NETs, not curable with surgery.
  • Patients must have measurable disease using the RECIST v1.1 criteria;
  • Indication for cytotoxic systemic chemotherapy validated by the dedicated Multidisciplinary Tumor Board;
  • MRI or TAP CT scan with contrast agents within 4 weeks +/- 1 week before beginning of treatment;
  • Tumor tissue available (fresh frozen or paraffin-embedded) in order to search for the methyl guanine methyltransferase (MGMT) status;
Show all 11Show fewer
  • Patients with childbearing potential should use effective contraception during the study and the following 6 months;
  • Covered by a Healthcare System where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research;
  • Subject able to understand and willing to sign a written informed consent document;
  • Signed written informed consent obtained prior to any study-specific screening procedures.
  • Previous treatments such as surgery, radiofrequency ablation, transarterial liver embolization, somatostatin analogs, interferon, everolimus or other targeted therapy, peptide receptor radionuclide treatment (PRRT) and chemotherapy (platin-etoposide, folfiri, paclitaxel or docetaxel) are allowed.

Who cannot join

  • Previous chemotherapy using Oxaliplatin or ALKY (streptozotocin, dacarbazin or temozolomide). Other chemotherapy (platin-etoposide, folfiri, paclitaxel or docetaxel) are allowed;
  • Pregnant or breastfeeding;
  • Men and women of childbearing age potential not using medically accepted contraceptive measures, as judged by the investigator;
  • Contraindication to any drug contained in the chemotherapy regimen;
  • Any significant disease which, in the investigator's opinion, excludes the patient from the study;
  • Under any administrative or legal supervision.

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

France19 sites

  • Hôpital Sud - CHU Amiens

    Amiens, 80054

  • CHU d'Angers

    Angers, 49933

  • Hôpital Estaing, CHU de Clermont-Ferrand

    Clermont-Ferrand, 63003

  • Hôpital Beaujon - APHP

    Clichy, 92118

  • Hôpital François Mitterrand - CHU Dijon Bourgogne

    Dijon, 21000

  • Centre Oscar Lambret

    Lille, 59020

  • Hôpital Claude Hurriet - CHRU Lille

    Lille, 59037

  • Hôpital Edouard Herriot - Hospices Civils de Lyon

    Lyon, 69003

  • Hôpital Privé Jean Mermoz

    Lyon, 69008

  • Institut Paoli Calmettes

    Marseille, 13009

  • Hôpital Saint Louis - APHP

    Paris, 75010

  • Hôpital Cochin - APHP

    Paris, 75014

  • CH Annecy Genevois

    Pringy, 74374

  • Hôpital Robert Debré - CHU Reims

    Reims, 51092

  • Hôpital Nord - CHU Saint Etienne

    Saint-Priest-en-Jarez, 42270

  • Institut de Cancérologie de la Loire

    Saint-Priest-en-Jarez, 42270

  • Hôpital Rangueil - CHU Toulouse

    Toulouse, 31059

  • Hôpital Trousseau - CHU Tours

    Tours, 37044

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

About this study

Neuroendocrine tumors (NET) are rare but their incidence is growing. Alkylating agents (ALKY) are one of the main systemic treatments used, at least for advanced duodeno-pancreatic NETs, with a response rate of 30 to 40% and a median progression-free survival of 4 to 18 months. Chemotherapy is one of the few therapeutic weapons, along with everolimus, somatostatin analogs, and metabolic radiotherapy, for lung NETs, called typical and atypical carcinoids, even if the level of proof of efficacy for these treatments is lower than for duodeno-pancreatic NETs. Considering the available retrospective data, O6-Methylguanine-DNA methyltransferase (MGMT) appears to be a predictive factor of the response to ALKY. Oxaliplatin (OX) has demonstrated an interesting activity, with response rates between 17% and 30%. In a first retrospective study we showed that Gemox is effective in NET, and more recently that its activity is similar to that of ALKYs, but without being influenced by the MGMT status. Prospective studies are needed but our data suggests that ALKY should be offered first to patients with methylated MGMT tumors while Oxaliplatin-based chemotherapy should be offered first to patients with unmethylated MGMT tumors.

In this project, we wish to evaluate the contribution of the MGMT methylation, evaluated in the tumor, in predicting the Objective Response (OR) in patients treated with ALKY and to evaluate a treatment with alkylating agents versus Oxaliplatin in patients with a duodeno-pancreatic or lung or unknown primitive NET.

Being tested
Oxaliplatin-based chemotherapy, Alkylating-based chemotherapy
Keywords
Neuroendocrine tumors, Methylation MGMT status, Alkylating agents, Oxaliplatin
Medical subject headings
Neuroendocrine Tumors

What participants receive

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

  • Oxaliplatin-based chemotherapyDrug

    The "oxaliplatin-based" group will receive gemox (gemcitabine-oxaliplatin, 1x/2 week); alternatively folfox (5 fluorouracil-leucovorin-oxaliplatin, 1x/2 week) or capox (capecitabine-oxaliplatin, 1x/3 week).

  • Alkylating-based chemotherapyDrug

    The "alkylating-based" group will receive CapTem regimen (capecitabine and temozolomide, /4 week), alternatively LV5FU2 (folinic acid-5 fluorouracil)-dacarbazine (1x/2 week) or LV5FU2 (folinic acid-5-fluorouracil)-streptozotocine (1x/2 week).

Study groups in NCT03217097
Study groupRoleWhat they receive
Unmethylated MGMT NET - OXExperimentalPatients with unmethylated MGMT NET will be randomly assigned (1:1) to either the alkylating-based chemotherapy arm or to the oxaliplatin-based chemotherapy arm. The "oxaliplatin-based" group will receive gemox (gemcitabine-oxaliplatin, 1x/2 week); alternatively folfox (5 fluorouracil-leucovorin-oxaliplatin, 1x/2 week) or capox (capecitabine-oxaliplatin, 1x/3 week).
Receives: Drug: Oxaliplatin-based chemotherapy
Unmethylated MGMT NET - ALKYActive comparatorPatients with unmethylated MGMT NET will be randomly assigned (1:1) to either the alkylating-based chemotherapy arm or to the oxaliplatin-based chemotherapy arm. The "alkylating-based" group will receive CapTem regimen (capecitabine and temozolomide, /4 week), alternatively LV5FU2 (folinic acid-5 fluorouracil)-dacarbazine (1x/2 week) or LV5FU2 (folinic acid-5-fluorouracil)-streptozotocine (1x/2 week).
Receives: Drug: Alkylating-based chemotherapy
Methylated MGMT NET - OXExperimentalPatients with methylated MGMT NET will be randomly assigned (2:1) to either the alkylating-based chemotherapy arm or to the oxaliplatin-based chemotherapy arm. The "oxaliplatin-based" group will receive gemox (gemcitabine-oxaliplatin, 1x/2 week); alternatively folfox (5 fluorouracil-leucovorin-oxaliplatin, 1x/2 week) or capox (capecitabine-oxaliplatin, 1x/3 week).
Receives: Drug: Oxaliplatin-based chemotherapy
Methylated MGMT NET - ALKYActive comparatorPatients with methylated MGMT NET will be randomly assigned (2:1) to either the alkylating-based chemotherapy arm or to the oxaliplatin-based chemotherapy arm. The "alkylating-based" group will receive CapTem regimen (capecitabine and temozolomide, /4 week), alternatively LV5FU2 (folinic acid-5 fluorouracil)-dacarbazine (1x/2 week) or LV5FU2 (folinic acid-5-fluorouracil)-streptozotocine (1x/2 week).
Receives: Drug: Alkylating-based chemotherapy

What is being measured

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

  1. Objective Response (OR) in patients treated with alkylating-based chemotherapy

    Objective Response (OR) in NETs patients treated with alkylating-based chemotherapy according to O6-Methyl guanine methyltransferase (MGMT) methylation status. The evaluation of OR is evaluation of complete response (CR) or partial response (PR) assessed by CT scan TAP or MRI with injection using the RECIST v1.1 criteria by centralized reading carried out by an expert radiologist blinded to the results of the MGMT methylation (methylated or un-methylated).

    Measured: 3 months

Secondary outcomes (6)

  1. Objective Response (OR) in patients treated with oxaliplatin-based chemotherapy

    Objective Response (OR) in NETs patients treated with oxaliplatin-based chemotherapy according to O6-Methyl guanine methyltransferase (MGMT) methylation status. The evaluation of OR is evaluation of complete response (CR) or partial response (PR) assessed by CT scan TAP or MRI with injection using the RECIST v1.1 criteria by centralized reading carried out by an expert radiologist blinded to the results of the MGMT methylation (methylated or un-methylated).

    Measured: 3 months

  2. Progression Free Survival (PFS) in patients treated with alkylating-based chemotherapy

    Progression Free Survival (PFS) in patients treated with alkylating-based chemotherapy according to MGMT methylation status. Progression Free Survival (PFS) is defined as the time from random assignment in a clinical trial to disease progression (assessed by CT scan TAP or MRI with injection, using the RECIST v1.1 criteria by centralized reading carried out by an expert radiologist blinded to the results of the MGMT methylation) or death from any cause.

    Measured: 3 months

  3. Progression Free Survival (PFS) in patients treated with oxaliplatin-based chemotherapy

    Progression Free Survival (PFS) in patients treated with oxaliplatin-based chemotherapy according to MGMT methylation status. Progression Free Survival (PFS) is defined as the time from random assignment in a clinical trial to disease progression (assessed by CT scan TAP or MRI with injection, using the RECIST v1.1 criteria by centralized reading carried out by an expert radiologist blinded to the results of the MGMT methylation) or death from any cause.

    Measured: 3 months

  4. Overall Survival (OS) in patients treated with alkylating-based chemotherapy

    Overall Survival (OS) in patients treated with alkylating-based chemotherapy according to MGMT methylation status. Overall Survival (OS) is defined as the time from random assignment to the date of death due to any cause, or to the date of censoring at the last time the subject was known to be alive in intention-to-treat populations

    Measured: 3 months

  5. Overall Survival (OS) in patients treated with oxaliplatin-based chemotherapy

    Overall Survival (OS) in patients treated with oxaliplatin-based chemotherapy according to MGMT methylation status. Overall Survival (OS) is defined as the time from random assignment to the date of death due to any cause, or to the date of censoring at the last time the subject was known to be alive in intention-to-treat populations

    Measured: 3 months

  6. Objective Response (OR) assessed by immunochemistry on tissue

    Objective Response (OR) at 3 months assessed by RECIST v1.1 criteria in patients with unmethylated MGMT NETs and in patients with methylated MGMT NETs evaluated with immunochemistry (IHC) on tissue

    Measured: 3 months

Timeline

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

  1. First posted13 Jul 2017
  2. Study start16 Oct 2018
  3. Primary completion31 Jan 2022
  4. Study completion25 Apr 2022

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 N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
116 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03217097
Sponsor's protocol ID
69HCL17_0284
Acronym
MGMT-NET
Status last verified
Nov 2022
First submitted
12 Jul 2017
Last updated
21 Nov 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Lemelin A, Barritault M, Hervieu V, Payen L, Peron J, Couvelard A, Cros J, Scoazec JY, Bin S, Villeneuve L, Lombard-Bohas C, Walter T; MGMT-NET investigators. O6-methylguanine-DNA methyltransferase (MGMT) status in neuroendocrine tumors: a randomized phase II study (MGMT-NET). Dig Liver Dis. 2019 Apr;51(4):595-599. doi: 10.1016/j.dld.2019.02.001. Epub 2019 Feb 14.

    PubMed 30824408

  • Walter T, Lecomte T, Hadoux J, Niccoli P, Saban-Roche L, Gaye E, Guimbaud R, Baconnier M, Hautefeuille V, Do Cao C, Petorin C, Hentic O, Perrier M, Aparicio T, Scoazec JY, Bonjour M, Gibert B, Hervieu V, Poncet D, Barritault M, Gerard L, Durand A; "Groupe d'etude des tumeurs endocrines (GTE)" and the French ENDOCAN-RENATEN network. Oxaliplatin-Based Versus Alkylating Agent in Neuroendocrine Tumors According to the O6-Methylguanine-DNA Methyltransferase Status: A Randomized Phase II Study (MGMT-NET). J Clin Oncol. 2025 Mar 10;43(8):960-971. doi: 10.1200/JCO.23.02724. Epub 2024 Nov 25.

    PubMed 39586038

Questions about this trial

What is this clinical trial studying?

A study testing Oxaliplatin-based chemotherapy and Alkylating-based chemotherapy in people with Neuroendocrine Tumors, run by Hospices Civils de Lyon at 19 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 11 inclusion and 6 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 21 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 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.

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?

Objective Response (OR) in patients treated with alkylating-based chemotherapy (time frame: 3 months). 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 NCT03217097, which also lists 2 linked publications.

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 21 Nov 2025.

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