Repurposing the Antipsychotic Drug Chlorpromazine as a Therapeutic Agent in the Combined Treatment of Newly Diagnosed Glioblastoma Multiforme
Trial Snapshot
- Phase
- Phase 2
- Sponsor
- Enrollment
- 41
- Locations
- 3
- Primary Endpoint
- Evaluation of toxicity
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
- •Progression-free patients after having undergone maximal safe debulking surgery when feasible or biopsy, and
- •Patients undergone completed standard concomitant chemo-radiotherapy with temozolomide
- •Patients with provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses.
- •Patients (both males and females) should employ adequate contraceptive measures which should be maintained during the whole duration of the trial
- •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 exclusion criteria apply:
- •Treatment with any of the following:
- •Any other chemotherapy, immunotherapy or anticancer agents within 4 weeks before enrollment in the study.
- •Any investigational agents or study drugs from a previous clinical study within 30 days before the first dose of study treatment.
- •MGMT methylated
- •As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including: uncontrolled hypertension; active bleeding diatheses; active hepatitis B virus (HBV), hepatitis C virus (HCV) or HIV infection. Screening for chronic conditions is not required; inadequate bone marrow reserve or organ function, as demonstrated by laboratory parameters.
- •Judgment by the investigator that the patient should not participate to the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
- •Contraindications to MRI and or magnetic resonance spectroscopy (MRS).
- •Patients not able to sign informed consent.
Arms & Interventions
Standard protocol plus chlorpromazine (CPZ)
Combination of chlorpromazine to the standard treatment with temozolomide in the sole adjuvant phase of the standard protocol.Chlorpromazine will be administered at a dose of 50 mg/day concomitantly with the adjuvant treatment with temozolomide (TMZ)
Intervention: Chlorpromazine Pill (Drug)
Outcomes
Primary Outcomes
Evaluation of toxicity
Time Frame: 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)
Time Frame: 6 months
Effect of of adding CPZ to the standard GBM therapy, when compared with the standard therapy alone
Secondary Outcomes
- Evaluation of tumor response(6 months)
- Overall survival (OS)(6 months)
Investigators
Marco G Paggi, MD, PhD
Medical Doctor, Clinical Pharmacologist
Regina Elena Cancer Institute