Lutathera for the treatment of recurrent Meningioma (LUMEN-1)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Mar 2025 → ongoing

Decision date (initial)

2024-12-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis · European Organisation for Research and Treatment of Cancer (EORTC)

External identifiers

EU CT number

2024-513443-93-00

ClinicalTrials.gov

NCT06326190

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety, Others

This randomized phase II trial aims to assess whether using [177Lu]Lu-DOTATATE on recurrent meningioma shows sufficient antitumor activity to justify further investigation.

Secondary objectives 6

1. To assess in comparison to local standard of care the [177Lu]Lu-DOTATATE’s impact on radiological response
2. To assess in comparison to local standard of care the [177Lu]Lu-DOTATATE’s impact on overall survival
3. To assess in comparison to local standard of care the [177Lu]Lu-DOTATATE’s safety
4. To assess in comparison to local standard of care the [177Lu]Lu-DOTATATE’s impact on 4 key chosen HRQoL domains at week 24
5. To assess in comparison to local standard of care the [177Lu]Lu-DOTATATE’s impact on neurological function
6. To assess the [177Lu]Lu-DOTATATE’s tolerability

Conditions and MedDRA coding

Recurrent Meningioma without local treatment options (Surgery or Radiotherapy)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Adult patient ≥ 18 years of age
2. Histologically confirmed diagnosis of meningioma (all grades, 1-3 per WHO CNS5, are eligible)
3. WHO performance status 0-2
4. Measurable disease (at least 10 x 10 mm contrast enhancing lesion) on cranial MRI no more than two weeks prior to enrolment
5. Radiologically documented progression of any existing tumour (growth > 25% in the last two years) or appearance of new lesions (including intra- and extracranial manifestations)
6. Somatostatin receptor (SSTR)-positive confirmed by PET imaging with scan performed within four weeks before randomization (baseline SSTR-PET is considered as positive when meningioma uptake intensity exceeds a SUVmax of 2.3).
7. At least one prior surgery and one line of external beam radiotherapy for meningioma, if technically feasible
8. Adequate liver, renal and haematological function within four weeks prior to enrolment
9. Participants must have the following electrolyte values within normal limits or corrected to be within normal limits with supplements prior to first dose of study medication: • Potassium (potassium level of up to 6.0 mmol/L is acceptable at study entry if associated with creatinine clearance ≥ 60 mL/min calculated using CKD-EPI formula). Mild decrease below lower limit of normal (LLN) is acceptable at study entry if considered not clinically significant by investigator. • Total magnesium, with the exception of magnesium level > ULN – 3.0 mg/dL (1.23 mmol/L) associated with creatinine clearance ≥ 60 mL/min calculated using CKD-EPI formula. Mild decrease below LLN is acceptable at study entry if considered not clinically significant by Investigator. • Total calcium (corrected for serum albumin) level of up to 12.5 mg/dL (3.1 mmol/L) is acceptable at study entry if associated with creatinine clearance ≥ 60 mL/min calculated using CKD-EPI formula. Mild decrease below LLN is acceptable at study entry if considered not clinically significant by Investigator. • Patients who are receiving corticosteroid treatment with dexamethasone, must be treated with a dose of ≤4 mg/day (or other corticosteroids equivalent dose) for a minimum of 7 days prior to the initiation of study treatment. • Women of childbearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 72 hours prior to enrolment. A positive urine pregnancy test result must immediately be confirmed using a serum test. A pregnancy test will have to be reported within 7 days prior to the first dose of the study treatment.
10. Patients of childbearing / reproductive potential should use adequate birth control measures during the study treatment period and for at least 7 months after the last dose of treatment. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly.
11. Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 7 months after the last study treatment.
12. Before patient 's enrolment, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion criteria 8

1. Local therapy (surgery and / or radiotherapy) indicated per local investigator. Note: in case of patients with multiple meningioma lesions, in whom resection and / or radiotherapy of individual lesions is indicated, patients may be included after local therapy (with a 4-week gap between surgery / end of radiotherapy and start of treatment), if at least one remaining lesion fulfils the inclusion criteria.
2. Any prior systemic treatment regardless of the timing.
3. Life expectancy is less than nine weeks.
4. Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the study treatment.
5. Contraindication to MRI, CT or PET
6. Unstable cardiac conditions (congestive heart failure, angina pectoris, myocardial infarction within one year before enrolment, uncontrolled hypertension, clinically significant arrhythmias)
7. Psychological, familial, sociological, or geographical conditions could potentially hamper compliance with the study protocol and follow-up schedule.
8. Known hypersensitivity to the active substance or to any excipients.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint in this phase II study is progression-free survival (PFS) computed based on MRI-based RANO meningioma response criteria as assessed by the local investigator.

Secondary endpoints 5

1. Best overall response (BOR, defined as complete response (CR), minor response (MR) or partial response (PR) during study treatment). Objective response (CR/MR/PR) rate and median CR/MR/PR duration. Complete response rate and median CR duration computed by MRI based on RANO meningioma response criteria as assessed by the local investigator.
2. Overall survival (OS), OS probability at 6 (OS6) and 12 months (OS12), median OS (mOS).
3. Safety (CTCAE v.5.0) and tolerability ([177Lu]Lu-DOTATATE only).
4. Change from baseline in HRQoL in terms of the global QoL, cognitive functioning, social functioning and fatigue at week 24.
5. Change of neurological function (NANO scale) from baseline during study treatment.

Investigational products

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

Test 1

Comparator 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Sponsor organisation

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Address

Emmanuel Mounierlaan 83 Bus 11

City

Sint-Lambrechts-Woluwe

Postcode

1200

Country

Belgium

Scientific contact point

Organisation

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Contact name

Stéphanie Kromar

Public contact point

Organisation

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Contact name

Vassilis Golfinopoulos

Third parties 3

Locations

8 EU/EEA countries · 29 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 62 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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