Clinical trial NCT04224441: Repurposing Chlorpromazine in the Treatment of Glioblastoma
Official title: Repurposing the Antipsychotic Drug Chlorpromazine as a Therapeutic Agent in the Combined Treatment of Newly Diagnosed Glioblastoma Multiforme
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Glioblastoma Multiforme
MGMT-Unmethylated Glioblastoma
Keywords: drug repurposing
antipsychotic drugs
glioblastoma
Lead sponsor: Regina Elena Cancer Institute
Sponsor class: OTHER
Collaborators: name: Regina Elena Cancer Institute
name: Carlo Besta Neurological Institute
name: Istituto Oncologico Veneto IRCCS
First posted: 2020-01-13
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Addition of chlorpromazine to the standard GBM treatment during the adjuvant phase of the therapeutic protocol in un-methylated GBM patients
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 exclusion criteria apply:

1. 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
2. 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.

4. 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.

5. Contraindications to MRI and or magnetic resonance spectroscopy (MRS). 6. Patients not able to sign informed consent.

Primary outcomes:
measure: Evaluation of toxicity
timeFrame: 6 months
measure: Progression-free survival (PFS)
timeFrame: 6 months
Secondary outcomes:
measure: Evaluation of tumor response
timeFrame: 6 months
measure: Overall survival (OS)
timeFrame: 6 months
Other outcomes:
Locations:
city: Roma
country: Italy
facility: Regina Elena Cancer Institute
state: Lazio
city: Milano
country: Italy
facility: Carlo Besta Neurological Institute
state: Lombardia
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
state: Veneto
Study officials:
affiliation: Regina Elena Cancer Institute
name: Marco G Paggi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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