An Italian multicenter trial with Temozolomide taken daily at low doses continuously in patients with well differentiated neuroendocrine neoplasia (NENs) and in a clinical frailty status

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Istituto Europeo Di Oncologia S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Jan 2022 → ongoing

Decision date (initial)

2024-03-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-510898-24-00

EudraCT number

2020-005393-10

ClinicalTrials.gov

NCT05554003

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

Progression free survival (PFS).

Secondary objectives 6

1. Objective response rate (ORR) that means complete response (CR) + partial response (PR) in progressive, metastatic, low grade NENs.
2. Duration of response.
3. Overall survival (OS).
4. Safety.
5. Quality of life (QoL)
6. Centralized evaluation of O6-methylguanine-DNA-methyltransferase (MGMT) status in tumor tissue to correlate clinical outcomes and MGMT status and validate the method of MGMT determination.

Conditions and MedDRA coding

Patients with well differentiated neuroendocrine neoplasia (NENs) not eligible for active antitumoral treatments due to their clinical conditions.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Age > 18 years
2. Histologically proven diagnosis of low grade GEP-NENs (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)
5. Functioning/non functioning
6. Clinical and/or radiological 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 5

1. 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;
2. 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
3. Known 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
4. Patients treated with systemic therapies (chemotherapy, interferon-alpha, somatostatin analogues, molecular target therapies) within 1 month prior to screening visit
5. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression free survival (PFS)

Secondary endpoints 6

1. Objective response rate (ORR) that means complete response (CR) + partial response (PR) in progressive, metastatic, low grade NENs
2. Duration of response
3. Overall survival (OS).
4. Safety
5. Quality of life (QoL)
6. Centralized evaluation of O6-methylguanine-DNA-methyltransferase (MGMT) status in tumor tissue to correlate clinical outcomes and MGMT status and validate the method of MGMT determination

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Istituto Europeo Di Oncologia S.r.l.

Sponsor organisation

Istituto Europeo Di Oncologia S.r.l.

Address

Via Giuseppe Ripamonti 435

City

Milan

Postcode

20141

Country

Italy

Scientific contact point

Organisation

European Institute Of Oncology S.r.l.

Contact name

Francesca Spada

Public contact point

Organisation

European Institute Of Oncology S.r.l.

Contact name

Francesca Spada

Third parties 1

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

3 submissions — initial application plus substantial / non-substantial modifications