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Study of Adding or Not Liposomal Transcrocetin (L-TC) With Concomitant HypoFractionated Radiation ThErapy and TEmozolomide in Newly Diagnosed GLioblastoma (GBM) Patients

Phase 3
Not yet recruiting
Conditions
Glioblastoma
Interventions
Drug: Administration of L-TC
Other: Radiotherapy plus Temozolomide
Registration Number
NCT06477939
Lead Sponsor
Institut de cancérologie Strasbourg Europe
Brief Summary

This is phase III randomized, multicenter study adding or not intra-venous Liposomal Trasncrocetin (L-TC) to hypofractionated radiotherapy and concomitant Temozolomide followed by adjuvant Temozolomide in patients with histologically confirmed diagnosis of glioblastoma (GBM).

Detailed Description

During this trial the L-TC will be administered with the hypofractionated chemoradiation treatment to two cohorts:

* Cohort 1 - Non-operable population defined as patients with age less than 70-year-old and with biopsy alone, Karnofski index we propose to use the L-TC with the hypofractionated chemoradiation treatment to two cohorts:

* Cohort 2 - Elderly population defined as patients aged of more than 70-year-old and with Balducci score 1 or with low Balducci score 2 with Karnofski index ≥ 70% but whatever the quality of the surgery. For patients classified with a score of Balducci II, the geriatric assessment is essential. Although we are aware of the heterogeneity of patients in this group, we hope that the geriatric assessment will make it possible to reduce this heterogeneity by including only patients with a Charlson score \<4 and a score of autonomy IADL = 4

The eligible population will be randomized this combination with the treatment reference according to Perry et al publication

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
554
Inclusion Criteria
  • Cohort 1 - Non-operable patients

    • Patients aged at least 18 years old and ≤ 70 years old; male or female.
    • AND available biopsy
    • AND Karnofsky index ≥ 50% at Screening
  • Cohort 2 - Elderly patients

    • Patients aged > 70 years old; male or female
    • AND Balducci score I or II. For patients classified in Balducci II, only light Balducci II will be included, as defined by a Charlson score <4 and a score of autonomy IADL = 4. In the oncogeriatric evaluation, symptoms related to brain cancer disease have not to be considered for this criterion.
    • Karnofsky score (KPS) of ≥ 70% at Screening
    • Regardless resection
    • MRI at maximum 48h00 after surgery if partial, subtotal or macroscopically complete or supra-total resection
  • For both cohorts

    • Histologically confirmed diagnosis of glioblastoma (GBM) (2016 OMS classification) (Louis et al., 2016).
    • Contrast enhancing disease on MRI within 14 days prior to screening.
    • Within 2 weeks of baseline visit, hematologic and renal functions as specified: Absolute neutrophil count ≥ 1500/mm3, platelets ≥ 100,000/mm3, Hgb ≥ 9.0g/dL, creatinine ≤ 1.7mg/dl, total bilirubin ≤ 1.5mg/dL, blood urea nitrogen (BUN) within 2 times the upper limit of normal, transaminases ≤ 4 times above the upper limits of the institutional norm.
    • Sexually active patients must use an acceptable method of contraception while receiving doses of study medication.
    • Females of childbearing potential must have a negative serum or urine pregnancy test at screening and have additional pregnancy tests during study.
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Exclusion Criteria

• For both cohorts

  • Any previous radiotherapy (RT) of the brain whatever the interval between previous brain RT and diagnoses of GBM)
  • Any previous treatment of the GBM (except surgery) such as chemotherapy (including Gliadel wafer or gliasite application), immunotherapy, therapy with a biologic agent, hormonal therapy or Carmustine implant for brain tumors or immunotherapy, including vaccination (whatever the interval between previous treatment and diagnoses of GBM). Glucocorticoid therapy is allowed.
  • Previous digestive disease with mis-absorption such as Crohn disease or chronic colitis
  • Ongoing diarrhea grade ≥ 2 in the NCI CTCAE V5.0 (whatever the cause)
  • Inclusion in another trial in the 30 previous days
  • Patient who cannot undergo MRI
  • Pregnant or lactating woman.
  • Serious concurrent infection or medical illness that would jeopardize the ability of the patient to receive study treatment with reasonable safety.
  • Patients with previous cancer (< 5 years) except basocellular skin tumors and in situ cervix tumor
  • Patient has a known hypersensitivity to crocetins, L-TC or any of its excipients.
  • Contraindication of temozolomide as described in the Summary of product characteristics.
  • Patient who cannot understand French language.
  • Patient without French National Health insurance
  • Patient who cannot be reliable for follow-up
  • Patient under law protection
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Radiotherapy plus TemozolomideAdministration of L-TC-
Administration of L-TC on top of Radiotherapy plus TemozolomideRadiotherapy plus Temozolomide-
Primary Outcome Measures
NameTimeMethod
Overall SurvivalUp to 24 months

Overall Survival (OS) is defined as the length of time from the date of tumor resection surgery or definitive biopsy to the date of death.

Secondary Outcome Measures
NameTimeMethod
Quality of life (GBM module)Up to 24 months

EORTC 20-Item QOL-Brain Neoplasm (QLQ-BN20)

Evaluation of hypoxia markersUp to 24 months

Hypoxia imaging markers between two groups: comparison of volumetric metrics

Quality of lifeUp to 24 months

European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire (QLQ-C30)

Progression-Free Survival (PFS)Up to 24 months

RANO criteria will be used to evaluate response

Quality of life (specific for elderly population)Up to 24 months

Quality-of-Life Questionnaire EORTC Elderly Cancer Patients (EORTC QLQ-ELD14)

ToleranceUp to 24 months

EORTC Elderly Cancer Patients (EORTC QLQ-ELD14)

Trial Locations

Locations (1)

Institut de cancérologie Strasbourg Europe

🇫🇷

Strasbourg, France

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