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Updated: Jan 28, 2026

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Published on: August 14, 2012
O6-methylguanine-DNA methyltransferase (MGMT) status in neuroendocrine tumors: a randomized phase II study (MGMT-NET)
Annie Lemelin1, Marc Barritault2, Valérie Hervieu3
1Department of Medical Oncology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France.
Introduction:
Neuroendocrine tumors (NETs) are rare, but their incidence is rising. Alkylating agents (ALKY), temozolomide and streptozotocin, are the main chemotherapies used for advanced pancreatic NETs. According to retrospective data, O6-methylguanine-DNA methyltransferase (MGMT) status appears to be a predictive factor of the response to ALKY.
Aims:
The main objective is to evaluate the value of tumor MGMT promoter (pMGMT) methylation in the prediction of the objective response (OR) at 3 months in patients treated with ALKY. Secondly, we will evaluate the value of MGMT immunohistochemistry and the efficacy of treatment with ALKY vs. oxaliplatin-based chemotherapy (Ox).
Materials And Methods:
A national, prospective, open-label, randomized, controlled and multicenter trial was designed. Main inclusion criteria are: adult patients with well-differentiated advanced duodeno-pancreatic, lung, or unknown primitive NETs with a validated indication for chemotherapy. pMGMT methylation will be assessed by pyrosequencing, but an ancillary study will compare this technique with others ones including MGMT immunohistochemistry.
Results:
A total of 104 patients will be randomly assigned (1:1 for unmethylated or 2:1 for methylated pMGMT NETs) to either the ALKY arm or to the Ox arm.
Conclusion:
Recruitment started on October 16, 2018 (NCT03217097) and will be open in 21 centers in France.
Insights
Tumor O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation may predict response to alkylating agents (ALKY) chemotherapy in advanced neuroendocrine tumors (NETs). This trial investigates MGMT status and compares ALKY with oxaliplatin-based regimens.
Area of Science:
- Oncology
- Molecular Diagnostics
- Clinical Trials
Background:
- Neuroendocrine tumors (NETs) are rare but increasing in incidence.
- Alkylating agents (temozolomide, streptozotocin) are standard chemotherapy for advanced pancreatic NETs.
- O6-methylguanine-DNA methyltransferase (MGMT) status may predict response to alkylating agents.
Purpose of the Study:
- To evaluate the predictive value of tumor MGMT promoter (pMGMT) methylation for objective response to alkylating agents (ALKY) in advanced NETs.
- To assess MGMT immunohistochemistry as a predictive biomarker.
- To compare the efficacy of ALKY versus oxaliplatin-based chemotherapy (Ox).
Main Methods:
- A national, prospective, randomized, controlled, multicenter trial.
- Inclusion of adult patients with advanced, well-differentiated NETs requiring chemotherapy.
- Assessment of pMGMT methylation by pyrosequencing, with ancillary comparison to immunohistochemistry.
Main Results:
- 104 patients will be randomized (1:1 or 2:1 based on pMGMT methylation status) to ALKY or Ox arms.
- The study aims to determine the predictive value of pMGMT methylation for treatment response.
- Comparative efficacy of two chemotherapy regimens will be analyzed.
Conclusions:
- MGMT promoter methylation status is being investigated as a predictive biomarker for alkylating agent chemotherapy in advanced NETs.
- This trial will provide insights into optimizing chemotherapy selection for NET patients based on molecular markers.
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