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Neuroendocrine TumorsPhase 2MeTeNCT05554003

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

A Phase 2 study testing Temozolomide capsule in people with Neuroendocrine Tumors and Frailty, run by European Institute of Oncology at 1 site in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Study 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Temozolomide capsule
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
1 siteItaly
Study dates
14 Jan 2022to 31 Dec 2024
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 > 18 years.
  • 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.
  • Advanced disease (unresectable locally advanced or metastatic).
  • 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
  • Functioning/non functioning.
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  • Morphological progressive disease (CT scan or MRI).
  • Recovery from toxicities related to any prior treatments, adequate wash-out period from previous treatments.
  • Ability to swallow pills.
  • 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.

Who cannot join

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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Francesca Spada, MD, PhD contact

+390257489258

francesca.spada@ieo.it

Italy1 site, 1 recruiting
  • European Institute of Oncology, IEO, IRCCS

    Milan, 20141

    Darina Tamayo, PharmSc., +39(0)294372686, darina.tamayo@ieo.it

    Cristina Mazzon, Ph.D., +39(0)294372686, cristina.mazzon@ieo.it

    Recruiting

Other trials in Italy

About this study

Official title: An Italian Multicenter Phase II Trial of Metronomic Temozolomide in Unfit Patients With Advanced Neuroendocrine Neoplasms (NENs): MeTe Study

Study 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.

Read the detailed description

Study design and trial duration This is an italian multicenter phase II trial of metronomic temozolomide in unfit patients with advanced NENs. The accrual will last 1-year and the follow up 2-year for a global 3-year period.

Objectives Primary endpoint Progression free survival (PFS).

Secondary endpoint Overall response rate (ORR) Duration of response (DOR) Overall survival (OS) Safety Quality of life (QoL)

Exploratory endpoint To evaluate O6 methylguanine DNA methyltransferase (MGMT) status in tumor tissue to validate the methods of MGMT determining and correlation with clinical outcomes

Overview on the study design Prospective analyses of consecutively NEN patients treated at Istituto Europeo di Oncologia IRCCS and participant centers between the end of 2021 and 2024 will be conducted. All patients who potentially benefit by these therapies will be proposed to participate to the study. The patient notes will then be assessed for eligibility as defined in the next section.

Treatment drug and schedule The regimen consists of oral temozolomide 60 mg once daily fasting continuously (28-day cycles)

Being tested
Temozolomide capsule
Keywords
Temozolomide, Neuroendocrine tumors, NETs, NENs, Unfit, Chemotherapy, Metronomic, Advanced, Phase II, Open label
Medical subject headings
Neuroendocrine Tumors, Frailty

What participants receive

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

  • Temozolomide capsuleDrug

    Metronomic temozolomide 60 mg/die continuously

Study groups in NCT05554003
Study groupRoleWhat they receive
Metronomic TemozolomideExperimentalMetronomic Temozolomide in unfit patients with advanced neuroendocrine neoplasms (NENs) Dosage and schedule: 60 mg/die continuosly
Receives: Drug: Temozolomide capsule

What is being measured

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

  1. Progression free survival (PFS).

    PFS will be defined as the time from starting treatment to documented disease progression or death from any cause. For patients without documented progression or death at the time of analysis, PFS will be censored at the last actual visit date of tumor evaluation.

    Measured: 3 years

Secondary outcomes (5)
  1. Objective response rate (ORR).

    ORR will be defined as the percentage of patients with complete responses (CR) or partial responses (PR). Patients for whom overall best response is not CR or PR, as well as patients without any post baseline tumor assessment, will be considered non responders.

    Measured: 3 years

  2. Duration of response (DoR)

    DOR will be defined as the time from the first documented objective response of PR or CR, whichever is noted earlier, to disease progression or death (if death occurs before progression is documented). DOR will be defined for responders only, i.e.

    patients with a CR or PR. DOR for patients who have not progressed or died at the time of analysis will be censored at the date of their last tumor assessment.

    Measured: 3 years

  3. Overall survival (OS)

    Overall survival (OS). OS will be defined as the time from starting treatment to death from any cause. Patients alive at the date of data cut off for analysis will be censored at the last date known to be alive.

    Measured: 3 years

  4. Incidence of adverse events (AEs)

    Incidence of adverse events (AEs), with severity determined through use of the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0); change from baseline in targeted vital signs and physical findings ; change from baseline in targeted clinical laboratory test results

    Measured: 3 years

  5. Quality of life (QoL)

    Mean changes from baseline score in patient function (physical, role, social, emotional, cognitive) and disease/treatment related symptoms by cycle, as assessed by a ll function scales and symptom items/scales of the EORTC QLQ C30, EORTC GI NET 2 and G8 test for frail elderly patients.

    Measured: 3 years

Timeline

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

  1. First posted26 Sep 2022
  2. Study start14 Jan 2022
  3. Primary completion31 Dec 2024 (estimated)
  4. Study completion31 Dec 2024 (estimated)

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Open label
Masking
None (open label)
Enrolment
46 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05554003
Sponsor's protocol ID
IEO1411
Acronym
MeTe
Status last verified
Nov 2024
First submitted
21 Sep 2022
Last updated
18 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Lambrescu I, Fica S, Martins D, Spada F, Cella C, Bertani E, Rubino M, Gibelli B, Grana C, Bonomo G, Funicelli L, Ravizza D, Pisa E, Zerini D, Ungaro A, Fazio N; IEO ENETS Center of Excellence for GEP NET. Metronomic and metronomic-like therapies in neuroendocrine tumors - Rationale and clinical perspectives. Cancer Treat Rev. 2017 Apr;55:46-56. doi: 10.1016/j.ctrv.2017.02.007. Epub 2017 Feb 24.

    PubMed 28314176
  • Koumarianou A, Kaltsas G, Kulke MH, Oberg K, Strosberg JR, Spada F, Galdy S, Barberis M, Fumagalli C, Berruti A, Fazio N. Temozolomide in Advanced Neuroendocrine Neoplasms: Pharmacological and Clinical Aspects. Neuroendocrinology. 2015;101(4):274-88. doi: 10.1159/000430816. Epub 2015 Apr 29.

    PubMed 25924937
  • Weller M, Tabatabai G, Kastner B, Felsberg J, Steinbach JP, Wick A, Schnell O, Hau P, Herrlinger U, Sabel MC, Wirsching HG, Ketter R, Bahr O, Platten M, Tonn JC, Schlegel U, Marosi C, Goldbrunner R, Stupp R, Homicsko K, Pichler J, Nikkhah G, Meixensberger J, Vajkoczy P, Kollias S, Husing J, Reifenberger G, Wick W; DIRECTOR Study Group. MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial. Clin Cancer Res. 2015 May 1;21(9):2057-64. doi: 10.1158/1078-0432.CCR-14-2737. Epub 2015 Feb 5.

    PubMed 25655102

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Temozolomide capsule in people with Neuroendocrine Tumors and Frailty, run by European Institute of Oncology at 1 site in Italy.

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 10 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: looking for participants now, as of the sponsor's last update on 18 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Francesca Spada, MD, PhD (+390257489258, francesca.spada@ieo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (PFS). (time frame: 3 years). 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 NCT05554003, which also lists 3 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 18 Nov 2024.

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