Quality of life and neurocognitive functioning in diffuse low-grade glioma patients treated with Temozolomide: feasibility study - TEMOIN

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Regional Du Cancer De Montpellier

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2024-09-19

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516918-37-00

EudraCT number

2017-001108-31

ClinicalTrials.gov

NCT03257618

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Others

This study will evaluate the feasability in terms of participation and compliance of a complete neurocognitive, psychopathological and QoL assessment (baseline, 6 months and 12 months) in DLGG patients receiving TMZ as a first line treatment after surgery. The data collected in this feasability study will be used to formulate hypotheses for a future multicentric clinical study.

Secondary objectives 7

1. To assess the QoL in DLGG patients receiving TMZ
2. To assess the neurocognitive functioning in DLGG patients receiving TMZ
3. To assess the pathopsychological functioning in DLGG patients receiving TMZ
4. To estimate the percentage of patients experiencing a decline in his/her QoL, neurocognitive, or pathopsychological scores between the baseline evaluation and any further evaluation, in the absence of progressive disease or other factors potentially inducing an alteration of the QoL
5. To describe the tolerance of TMZ
6. Décrire le taux de réponse objective chez les patients porteurs d’un GDBG recevant du TMZ, la survie sans progression et la survie globale
7. To describe the progression-free survival (PFS) and overall survival (OS) in DLGG patients receiving TMZ.

Conditions and MedDRA coding

Diffuse low-grade gliomas

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Adult patient aged ≥ 18, no age limit
2. Histologically-proven DLGG
3. Patient receiving TMZ as a first line treatment after surgery, whatever the delay between the surgery and the introduction of TMZ
4. No previous oncologic treatment (except for surgery) for the DLGG;
5. Performance Status score ≤2
6. Absolute neutrophil count (ANC) ≥ 1500 cells/µL and platelet count ≥ 100 000 cells/µL
7. Total serum bilirubin concentration ≤ 1.5 x the upper limit of normal (UPN)
8. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤ 2.5 x the ULN ;
9. Serum creatine concentration ≤ 1.5 x the ULN
10. Negative pregnancy test in women of childbearing potential
11. Signature du consentement éclairé avant toute procédure de l’étude
12. Patient fluent in French
13. Patient affiliated to a French social security system

Exclusion criteria 13

1. Anaplastic glioma (WHO grade III glioma)
2. Impaired neurocognitive functioning defined by a score < 22 at the MoCA test
3. Visual or auditory deficit
4. Previous chemotherapy for the DLGG
5. Previous RT for the DLGG
6. Known hypersensitivity to any of the study drugs, or excipients in the formulation
7. Hypersensitivity to dacarbazine (DTIC);
8. Myélosuppression sévère;
9. Problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption;
10. Legal incapacity or physical, psychological social or geographical status interfering with the patient's ability to sign the informed consent or to terminate the study
11. Pregnant or breastfeeding women;
12. Men or women of childbearing potential who are unwilling to employ adequate contraception, from the beginning of the study until 6 months after administration of the last treatment dose;
13. Participation in another clinical trial within 30 days prior to study entry.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Feasability will be analyzed using two parameters: 1.participation rate: proportion of patients that consent to participate in the study among the screened patients. We expect that 80% of the sceened patients will consent to the study. 2. compliance rate: the proportion of included patients that will complete the evaluations at baseline, 6 months and 12 months. We expect that 80% of patients will be compliant.

Secondary endpoints 18

1. The total score obtained at the EORTC QLQ-C30 and the scores obtained at the different dimensions of the QLQ-C30 (ranged from 0 to 100) according to the EORTC’s instructions;
2. The total score obtained at the QLQ-BN20 and the scores obtained at the different dimensions of the QLQ-BN20 (ranged from 0 to 100) according to the EORTC’s instructions
3. Le score total obtenu au questionnaire IMF (Inventaire Multifactoriel de Fatigue)
4. The four scores obtained at the four subscales of the french FACT-Cog (Functional Assessment of Cancer Therapy-Cognitive Function) assessing the perceived cognitive impairments (from 0 to 72), the comments from others (from 0 to 16), the perceived cognitive abilities (from 0 to 16), and the impact on quality of life (from 0 to 28);
5. The percentage of patients experiencing a decline in the QoL scores: decline is defined as ≥ 20% of decrease with the following calcul: [(score at baseline – score at further evaluation)/score at baseline]*100.
6. The total score (from 0 to 50) obtained at the f-NART (French version of the National Adult Reading Test) according to the Mackinnon and Mulligan (2005)’s instructions;
7. The total score (from 0 to 30) obtained at the MoCA (Montreal Cognitive Assessment) according to the Nasreddine et al. (2012)’s instructions;
8. The index of psychomotor speed (ranged from 40 to 160) according to the Wechsler (2011)’s calculation rules, which are based on the scores obtained at the Digit-symbol substitution test and the Code test of the WAIS-IV.
9. The scores obtained at the HVLT-R (Revised Hopkins Verbal Learning Test) according to Rieu et al (2006)’s instructions: the number of correct free recalls (for each of the 3 trials), the total learned score, the number of correct delayed recalls, the recognition hits rate, the false positives rate, the discrimination rate, the number of intrusions and perseverations;
10. The four scores obtained at the complex Rey figure, as noticed in the instructions of Wallon and Mesmin (2009) (copy type, , timing, free immediate and delayed and recall);
11. The different scores obtained at the MemProsp tasks (both event and time-based tasks) according to Einstein and Mc Daniel (1990)’s instructions: number of correct prospective memory responses, number of calls for the time counter (over the entire session and within the last 30-second before the target), number of correct word ratings.
12. The timing (ms), the number and type of errors (flexibility, proximity or attentionnal) gathered at the TMT A and B (Trail Making Test A and B) as Ashendorf et al. (2008) and Godefroy et al. (2010) described in their instructions;
13. The timing (ms), the total number of omissions (from 0 to 35), and the difference between left omissions and right omissions gathered at the Bell’s test, according to the Rousseaux et al. (2001)’s instructions;
14. The number and percentage of patients who report high-grade (grade 3-4-5 according to the CTCAE-NCI criteria) adverse reactions of interest will be summarized for all treated patients;
15. The Objective Response Rate (ORR), defined as the number and percentage of patients with a best overall response of complete response (CR) or partial response (PR) recorded between the date of first dose of TMZ and the date of the objectively documented tumor progression according to the RANO criteria (van den Bent et al., 2011) in all treated patients
16. The proportion of patients experiencing a decrease of their tumor volume under TMZ. The tumor volume (cm3), determined on the T2/FLAIR sequence of the brain MRI (in DICOM format) using manual delineation of the tumor limits on each slide and calculation of the volume on a dedicated software;
17. The PFS, defined as the delay between the date of introduction of TMZ and the date of the progression (according to the RANO criteria) or death from any cause;
18. The OS, defined as the delay between the date of introduction of TMZ and death from any cause.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Regional Du Cancer De Montpellier

Sponsor organisation

Institut Regional Du Cancer De Montpellier

Address

208 Avenue Des Apothicaires

City

Montpellier Cedex 5

Postcode

34298

Country

France

Scientific contact point

Organisation

Institut Regional Du Cancer De Montpellier

Contact name

Project manager

Public contact point

Organisation

Institut Regional Du Cancer De Montpellier

Contact name

PROJECT MANAGER

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 5 files

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

Application history

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