Glioblastoma Multiforme, MGMT-Unmethylated Glioblastoma
Conditions
Keywords
drug repurposing, antipsychotic drugs, glioblastoma
Brief summary
This study evaluates the addition of chlorpromazine to the first-line therapeutic protocol, i.e. maximal well-tolerated surgical resection followed by radiotherapy plus concomitant and adjuvant chemotherapy with temozolomide, in newly diagnosed glioblastoma multiforme patients carrying a hypo-methylated O6-methylguanine-DNA-methyltransferase (MGMT) gene
Detailed description
Chlorpromazine (CPZ, Largactil, Thorazine) is a potent antagonist of the dopamine receptor D2 (DRD2) and has been effectively and safely employed for over half a century in the treatment of psychiatric disorders. CPZ displays a series of remarkable bio-molecular effects in cancer cells, as inhibition of cell growth, nuclear aberrations, inhibition of the phosphoinositide 3-kinase/mammilian target of rapamycin (PI3K/mTOR) axis, induction of cytotoxic autophagy, inhibition of glutamate and DRD2 receptors.
Interventions
DRUGChlorpromazine Pill
The experimental treatment involves the combination of chlorpromazine to the standard treatment with temozolomide solely in the adjuvant phase (after radio-chemotherapy, temozolomide for 5 days every 28, at a dose of 150-200 mg/mq for 6 cycles) of the Stupp protocol. Chlorpromazine will be administered at a dose of 50 mg/day concomitantly with the adjuvant treatment with temozolomide
Sponsors
Regina Elena Cancer Institute
Carlo Besta Neurological Institute
Istituto Oncologico Veneto IRCCS
Marco G Paggi, MD, PhD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Addition of chlorpromazine to the standard GBM treatment during the adjuvant phase of the therapeutic protocol in un-methylated GBM patients
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Newly diagnosed histologically-confirmed supra-tentorial GBM (World Health Organization grade IV) patients. Whenever feasible, patients will undergo maximal surgical resection or debulking, although patients with inoperable glioblastomas are also eligible. 2. Progression-free patients after having undergone maximal safe debulking surgery when feasible or biopsy, and 3. Patients undergone completed standard concomitant chemo-radiotherapy with temozolomide 4. Patients with provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses. 5. Patients (both males and females) should employ adequate contraceptive measures which should be maintained during the whole duration of the trial 6. Additional eligibility criteria include: age between 18 and 70; Karnofsky Performance Status (KPS) score of 70 or higher; adequate kidney, liver, bone marrow, and cardiac function; total serum bilirubin level and liver- function values; isocitrate dehydrogenase 1/2 (IDH1/2) mutational status; MGMT methylation status assessment.
Exclusion criteria
Patients should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of toxicity | 6 months | Toxicity evaluation of the combined treatment. Subjects will be evaluated for symptoms and adverse effects according to the NCI-CTCAE version 5.0 grading tool |
| Progression-free survival (PFS) | 6 months | Effect of of adding CPZ to the standard GBM therapy, when compared with the standard therapy alone |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of tumor response | 6 months | Effect of of adding CPZ to the standard glioblastoma multiforme (GBM) therapy, when compared with the standard therapy alone |
| Overall survival (OS) | 6 months | Effect of of adding CPZ to the standard glioblastoma multiforme (GBM) therapy, when compared with the standard therapy alone |
Countries
Italy
Contacts
Primary ContactAndrea Pace, MD
Backup ContactDiana Giannarelli, PhD
Outcome results
None listed