​​Lomustine with or without a second round of brain radiation for the reappearance of glioblastoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

European Organisation For Research And Treatment Of Cancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 Mar 2024 → ongoing

Decision date (initial)

2024-02-26

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

EU Grant - HORIZON-MISS-2022-CANCER-01-03 (Grant 101103655)

External identifiers

EU CT number

2023-505267-36-00

ClinicalTrials.gov

NCT05904119

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Efficacy

The primary objective is to show that overall survival (OS) with lomustine plus reirradiation is superior compared to lomustine monotherapy for first progression of glioblastoma

Secondary objectives 7

1. To show that progression-free survival (PFS) is improved with lomustine plus reirradiation compared to lomustine monotherapy
2. To assess the toxicity profile of lomustine plus reirradiation
3. To assess neurocognitive functioning of lomustine plus reirradiation
4. To assess whether the lomustine plus reirradiation improves QoL deterioration-free survival (QDFS) with particular interest in global health quality of life (GHQ) as compared to lomustine monotherapy
5. To transform self-reported quality of life data from the QLQC30 into health utility values, ready to be used in subsequent health economic analyses
6. To show that response is improved with lomustine plus reirradiation
7. To assess health-related quality of life of all other scales from the QLQ-C30, QLQ-BN20 and the item list (IL46) over time.

Conditions and MedDRA coding

Glioblastoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Before patient’s enrolment, written informed consent must be given according to ICH/GCP, and national/local regulations.
2. Patients of childbearing / reproductive potential must agree to use adequate birth control measures during the study treatment period and for at least 6 months after the last dose of study 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.
3. Patients with first progression or recurrent glioblastoma after first-line treatment with biopsy or maximal safe resection and standard radiotherapy or chemoradiotherapy with recurrence occuring at least 6 months after the end of Prior radiotherapy Prior first line therapy may include: Any systemic antineoplastic treatment other than nitroureas , Tumour-treating fields, Conventionally fractionated or abbreviated (minimum 15 fractions) radiotherapy
4. Measurable disease according to RANO criteria with a maximum tumour diameter of 5 cm (local investigator assessment) Note 1: in case of multiple lesions, maximum cumulative CTV diameter of 5 cm treatable by 1 isocentre. Note 2: in case of surgery for recurrence, this criterion applies at the time of recurrence.
5. In case of surgery for recurrence: fully recovered from surgery, confirmation of recurrence by histology, and patient fit for treatment as per local investigator assessment. Note: residual and measurable disease after surgery is not required, provided that measurable disease was present before surgery.
6. Histologically proven diagnosis of glioblastoma, IDH wildtype per WHO 2021 classification and local assessment of tissue from diagnosis or recurrence
7. Stable or decreasing dose of steroids for 7 days prior to enrolment
8. Age ≥ 18 years
9. WHO Performance status of 0-2
10. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to enrolment
11. Candidates for treatment with lomustine as per physician’s assessment.

Exclusion criteria 12

1. Any prior anticancer treatment for recurrent glioblastoma (except surgery)
2. Concurrent or recent history (30 days prior to lomustine initiation) of varicella (infection or exposure) and herpes zoster
3. Known hereditary galactose intolerance, Lapp-lactase deficiency, or glucose-galactose malabsorption.
4. Patients with known pulmonary infiltration, interstitial pneumonia or pulmonary fibrosis and with a baseline below 70% of the predicted Forced Vital Capacity (FVC) or Carbon Monoxide Diffusing Capacity (DLCO)
5. Significant reduction in thrombocyte and/or leukocyte counts (leukocytes < 4 x 10^9 /L and the platelets < 100 x 10^9 /L) as well as severe renal impairment according to investigator's opinion
6. History or present acute leukaemia or any myeloid disease
7. Known hypersensitivity to the active components or excipients of lomustine
8. Known coeliac disease or wheat allergy
9. Live attenuated vaccine in the 3 months prior to lomustine initiation
10. Any serious or uncontrolled medical condition (e.g., infections, chronic alcoholism, drug addiction) or abnormality, in the judgment of the investigator that prohibits obtaining informed consent, safe participation and study completion
11. Known contraindication to imaging tracer or any product of contrast media and Magnetic Resonance Imaging (MRI) contraindications
12. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed and discussed with the patient before the enrolment in the trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is OS defined as the number of days from date of enrolment to the date of death due to any cause.

Secondary endpoints 7

1. PFS. Events are progressions based on Response Assessment in Neuro Oncology (RANO) criteria as determined by the local investigator
2. Objective and complete response per RANO criteria as assessed by the local investigator
3. Safety according to the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0 for toxicity and Serious Adverse Event reporting
4. QDFS. A deterioration event is defined as ≥10-point worsening from baseline in the GHQ without further improvement (i.e., no subsequent ≥10 point improvement) or death due to any cause
5. Neurocognitive functioning assessed by Mini Mental State Examination (MMSE).
6. Health utility, calculated from the collected patient-reported HRQoL data from the QLQ-C30 and patient demographics
7. Change scores. Changes in HRQoL from baseline in the GHQ/QoL, fatigue, nausea/vomiting, physical, role and social functioning scale scores assessed over time will be evaluated descriptively. Descriptive summaries such as median, range (minimum, maximum), IQR, mean and standard deviation will be provided for all the other scales from the QLQ-C30, QLQ-BN20 and the item list (IL46).

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

European Organisation For Research And Treatment Of Cancer

Sponsor organisation

European Organisation For Research And Treatment Of Cancer

Address

Emmanuel Mounierlaan 83 Bus 11

City

Sint-Lambrechts-Woluwe

Postcode

1200

Country

Belgium

Scientific contact point

Organisation

European Organisation For Research And Treatment Of Cancer

Contact name

Stephanie Kromar

Public contact point

Organisation

European Organisation For Research And Treatment Of Cancer

Contact name

Vassilis Golfinopoulos

Third parties 1

Locations

10 EU/EEA countries · 41 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Documents 88 files

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

Application history

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