Annie Lemelin1, Marc Barritault2, Valérie Hervieu3, Léa Payen4, Julien Péron5, Anne Couvelard6, Jérome Cros7, Jean-Yves Scoazec8, Sylvie Bin9, Laurent Villeneuve9, Catherine Lombard-Bohas1, Thomas Walter10. 1. Department of Medical Oncology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France. 2. Departement of Molecular Biology, Multi-Site Pathology Institute of the Hospices Civils de Lyon-East Site, GHE University Hospital, Bron, France. 3. Institute of Multi-Site Pathology of the HCL-Est Site, GHE University Hospital, Bron, France. 4. CIRCAN (CIRculating CANcer) Platform, GHS University Hospital, Pierre-Benite, France. 5. Department of Biostatistics, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, France. 6. Department of Pathology, Bichat Hospital, Paris, France. 7. Department of Pathology, Beaujon University Hospital, Clichy, France. 8. Gustave Roussy Cancer Campus, Department of Surgical and Molecular Pathology, Villejuif, France. 9. Pole Information Médical Recherche, Clinical Research Department, Lyon, France. 10. Department of Medical Oncology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France. Electronic address: Thomas.walter@chu-lyon.fr.
Abstract
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.
RCT Entities:
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 tumorMGMT 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.
Authors: Vanessa Lakis; Rita T Lawlor; Felicity Newell; Ann-Marie Patch; Andrea Mafficini; Anguraj Sadanandam; Lambros T Koufariotis; Rebecca L Johnston; Conrad Leonard; Scott Wood; Borislav Rusev; Vincenzo Corbo; Claudio Luchini; Sara Cingarlini; Luca Landoni; Roberto Salvia; Michele Milella; David Chang; Peter Bailey; Nigel B Jamieson; Fraser Duthie; Marie-Claude Gingras; Donna M Muzny; David A Wheeler; Richard A Gibbs; Massimo Milione; Paolo Pederzoli; Jaswinder S Samra; Anthony J Gill; Amber L Johns; John V Pearson; Andrew V Biankin; Sean M Grimmond; Nicola Waddell; Katia Nones; Aldo Scarpa Journal: Commun Biol Date: 2021-02-03
Authors: Annamaria Colao; Filomena de Nigris; Roberta Modica; Claudio Napoli Journal: Front Endocrinol (Lausanne) Date: 2020-12-15 Impact factor: 5.555