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OncoMatch/Clinical Trials/NCT05554003

Metronomic Temozolomide in Unfit NENs Patients Metronomic Temozolomide in Unfit Patients With Advanced Neuroendocrine Neoplasms (NENs): MeTe Study

Is NCT05554003 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies Temozolomide capsule for neuroendocrine tumors.

Phase 2RecruitingEuropean Institute of OncologyNCT05554003Data as of May 2026

Treatment: Temozolomide capsuleStudy design and rationale: Neuroendocrine neoplasms (NENs ) represent a heterogeneous group of malignancies, which differ in terms of behavio r and prognosis. Most of t hem are advanced at diagnosis t herefore systemic treatment is proposed. While over the last years many advanced have been made especially in terms of molecular targeted therapies (MTA) like everolimus and sunitinib, chemotherapy i n NENs still represents a controversial question. Temozolomide has been reported to be active alone or in combination with other drugs in neuroendocrine neoplasms (NENs) from different origin. So far there is not universal agreement on the right setting an d way of administration of this therapy. Objective: This is a multicentric phase II prospective interventional study to evaluate the clinical features of patients, who are judged unfit for systemic treatments, consecutively treated with a metronomic Temozolomide chemotherapy schedule in Italian centers with expertise in NEN and to explore also the methylation status of O6-methylguanine-DNA-methyltransferase (MGMT) and the polymorphism of thymidylate synthase (TS) by pyrosequencing in those patients of which tissues were available. This study will allow a better understanding of the role of metronomic temozolomide chemotherapy in NENs patients and help clinicians in answering some of the outstanding questions on their management. Method: Prospective analysis of clinical data of patients unfit for chemotherapy consecutively treated with metronomic temozolomide regimen in Italian centers with expertise in clinical and research NEN activity, for one year from the start of the accrual. Planning of study: Data from NENs patients of any age treated at these centers will be retrieved by searching the hospital information system and analysed. Eligible study population: Patients with histological diagnosis of low grade advanced NEN treated unfit for systemic treatments, for one year from the start of the accrual. Endpoints and evaluation parameters: Description of efficacy and toxicity of Temozolomide regimen in patients with advanced NENs with different primary sites unfit for systemic treatment and explored the pote ntial correlation with clinical/biological factors.

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Extracted eligibility criteria

Cancer type

Neuroendocrine Tumor

Disease stage

Grade: low grade (who 2019 (gep-nens), travis classification (bronchial carcinoids))

Performance status

ECOG 2–2(Ambulatory, capable of self-care)

Prior therapy

Cannot have received: alkylating agent (temozolomide)

Patients pretreated with temozolomide

Cannot have received: systemic therapy (chemotherapy, interferon-alpha, somatostatin analogues, molecular target therapies)

Exception: within 1 month prior to screening visit

Patients treated with systemic therapies (chemotherapy, interferon-alpha, somatostatin analogues, molecular target therapies) within 1 month prior to screening visit

Lab requirements

Blood counts

absolute neutrophil count of ≥1.5×10^9/L, platelet count of ≥100×10^9/L, haemoglobin ≥9 g/dL; moderate medullary impairment (at least one of: Hb <10-8 gr/dl; WBC <3000-2000/mm3; platelets <75000-50000/mm3; neutrophil count <1500-1000/mm3) allowed

Kidney function

serum creatinine <1.5 times ULN or creatinine clearance ≥60 mL/min; renal failure (eGFR or CrCl 30-59 ml/min - G2) allowed

Liver function

serum total bilirubin <1.5 times ULN; ALT, AST, or alkaline phosphatase levels ≤2.5 times ULN (if known liver metastases ALT, AST, and ALP ≤3× the ULN); moderate liver failure (Child B 7-9) allowed

absolute neutrophil count of ≥1.5×10^9/L, platelet count of ≥100×10^9/L, haemoglobin ≥9 g/dL, serum total bilirubin <1.5 times ULN, ALT, AST, or alkaline phosphatase levels ≤2.5 times ULN (if known liver metastases ALT, AST, and ALP ≤3× the ULN), serum creatinine <1.5 times ULN or creatinine clearance ≥60 mL/min; moderate medullary impairment (at least one of: Hb <10-8 gr/dl; WBC <3000-2000/mm3; platelets <75000-50000/mm3; neutrophil count <1500-1000/mm3); renal failure (eGFR or CrCl 30-59 ml/min - G2) and/or moderate liver failure (Child B 7-9) allowed

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