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

Launched by EUROPEAN INSTITUTE OF ONCOLOGY · Sep 21, 2022

Keywords

ClinConnect Summary

The MeTe study is a clinical trial investigating the use of a specific chemotherapy called metronomic temozolomide in patients with advanced neuroendocrine neoplasms (NENs) who are considered unfit for standard treatments. Neuroendocrine neoplasms are a type of cancer that can be challenging to treat, especially when they are at an advanced stage. This trial aims to gather information about how effective and safe this chemotherapy is for these patients. The researchers will also look into certain biological markers in the patients' tumors to better understand how they might respond to treatment.

To be eligible for this trial, participants must be at least 18 years old and have a confirmed diagnosis of low-grade advanced NENs that cannot be surgically removed. They should also have specific health conditions that make them unfit for other systemic treatments. This includes having certain levels of blood counts or kidney and liver function. Participants will receive the metronomic temozolomide treatment for a year, and during that time, their health and response to the treatment will be closely monitored. It’s important for potential participants to know that they will need to agree to use effective contraception if they are of childbearing age, as the treatment can affect fertility.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Age \> 18 years.
• • 2. Histologically proven diagnosis of low grade GEP-NENs (including morphology and ki67 in accordance with WHO 2019 classification), bronchial carcinoids (in accordance with the Travis classification), low grade of unknown primary sites NENs.
• • 3. Advanced disease (unresectable locally advanced or metastatic).
• • 4. ECOG performance status 2 and/or moderate medullary impairment (at least one of the following criteria: Hb concentration \<10-8 gr/dl; WBC \<3000-2000/mm3; platelets \<75000-50000/mm3; neutrophil count \<1500-1000/mm3); renal failure (eGFR o CrCl 30-59 ml/min - G2) and/or moderate liver failure (Child B 7-9) and/or severe comorbidities and/or \> 3 prior systemic antitumor therapies (apart from SSA).
• • For all the parameters other than the above mentioned criteria n° 4 consider the following criteria (that must be associated with at least one of those above): absolute neutrophil count of ≥1.5×109/L, platelet count of ≥100×109/L, haemoglobin ≥9 g/dL, serum total bilirubin \<1.5 times the upper limit of normal (ULN) alanine aminotransferase (ALT), AST, or alkaline phosphatase levels ≤2.5 times the ULN (if known liver metastases ALT, AST, and ALP ≤3× the ULN), serum creatinine \<1.5 times ULN or creatinine clearance ≥60 mL/min as estimated by the Cockcroft-Gault formula
• • 5. Functioning/non functioning.
• • 6. Morphological progressive disease (CT scan or MRI).
• • 7. Recovery from toxicities related to any prior treatments, adequate wash-out period from previous treatments.
• • 8. Ability to swallow pills.
• • 9. Fertile men should agree to use effective contraceptive methods up to 6 months after the last temozolomide intake and should be informed about the possible irreversible infertility related to temozolomide intake.
• Exclusion Criteria:
• • 1. Patients pretreated with temozolomide.
• • 2. Are Women of Child-Bearing Potential (WOCBP) and men who are able to father a child, unwilling to use adequate contraception prior to trial entry, for the duration of trial participation and for at least 28 days 2 weeks after treatment has ended. Adequate methods of contraception and Women of Child-Bearing Potential; WOCBP childbearing potential who are nursing or are pregnant or do not agree to submit to pregnancy testing required by this protocol
• • 3. Patients that did not sign written informed consent prior to admission into the trial that is consistent with International Conference on Harmonisation (ICH)- Good Clinical Practice (GCP) guidelines and local law
• • 4. Knowed active hepatitis B infection (defined as presence of Hepatitis B (HepB) sAg and/or HepB DNA), active Hepatitis C (HEP C) infection (defined as presence of Hep C RNA) and/or known Human Immunodeficiency Virus (HIV) carrier.
• • 5. Patients treated with systemic therapies (chemotherapy, interferon-alpha, somatostatin analogues, molecular target therapies) within 1 month prior to screening visit
• • 6. Hypersensitivity to the active substance or to any of the excipients, hypersensitivity to dacarbazine (DTIC), known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery and stable for at least 3 months before study entry, pregnant or lactating females, patients on chronic treatment with valproic acid