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

Phase III Randomized Study of Adding or Not Liposomal Transcrocetin (L-TC) With Concomitant HypoFractionated Radiation ThErapy and TEmozolomide in Newly Diagnosed GLioblastoma (GBM) Patients to Evaluate Efficacy and Safety

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: Administration of L-TC; Other: Radiotherapy plus Temozolomide

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

• Study Type: Interventional
• Enrollment (Estimated): 554
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Manon VOEGELIN; Phone Number: +33 368767360; Email: promotion-rc@icans.eu

Study Locations

• France
  • Strasbourg, France, 67033
    • Institut de cancerologie Strasbourg Europe
    • Contact: Manon VOEGELIN; Phone Number: +33 368339523; Email: promotion-rc@icans.eu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Radiotherapy plus Temozolomide	Drug: Administration of L-TC; Administration of L-TC (300 mg) as an IV perfusion, before each radiotion session Radiotherapy : delivered at 40.5 Gy in 15 fractions of 2.7 Gy - One fraction a day 5 fractions per week + Temozolomide delivered at a dose of 75 mg per square meter per day, given 7 days per week from the first day of radiotherapy until the last day of radiotherapy, but for no longer than 25 days.
Experimental: Administration of L-TC on top of Radiotherapy plus Temozolomide	Other: Radiotherapy plus Temozolomide; Radiotherapy : delivered at 40.5 Gy in 15 fractions of 2.7 Gy - One fraction a day 5 fractions per week + Temozolomide delivered at a dose of 75 mg per square meter per day, given 7 days per week from the first day of radiotherapy until the last day of radiotherapy, but for no longer than 25 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	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.	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	RANO criteria will be used to evaluate response	Up to 24 months
Evaluation of hypoxia markers	Hypoxia imaging markers between two groups: comparison of volumetric metrics	Up to 24 months
Quality of life	European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire (QLQ-C30)	Up to 24 months
Quality of life (GBM module)	EORTC 20-Item QOL-Brain Neoplasm (QLQ-BN20)	Up to 24 months
Quality of life (specific for elderly population)	Quality-of-Life Questionnaire EORTC Elderly Cancer Patients (EORTC QLQ-ELD14)	Up to 24 months
Tolerance	EORTC Elderly Cancer Patients (EORTC QLQ-ELD14)	Up to 24 months

Collaborators and Investigators

• Sponsor: Institut de cancérologie Strasbourg Europe
• Collaborators: LEAF4Life, Inc.
• Investigators: Principal Investigator: Georges NOEL, MD, PhD, Institut de cancerologie Strasbourg Europe

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): December 31, 2032
• Study Completion (Estimated): December 31, 2032

Study Registration Dates

• First Submitted: June 21, 2024
• First Submitted That Met QC Criteria: June 26, 2024
• First Posted (Actual): June 27, 2024

Study Record Updates

• Last Update Posted (Actual): June 27, 2024
• Last Update Submitted That Met QC Criteria: June 26, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Hypoxia; Brain tumors; Liposomal transcrocetin
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: 2020-008; 2024-515666-13-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes