Repurposing Chlorpromazine in the Treatment of Glioblastoma (RACTAC)

Marco G Paggi, MD, PhD

Status and phase: Unknown; Phase 2

Conditions: Glioblastoma Multiforme; MGMT-Unmethylated Glioblastoma

Treatments: Drug: Chlorpromazine Pill

Study type: Interventional

Funder types: Other

Identifiers

NCT04224441

2019-001988-75

Details and patient eligibility

About

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

Full 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.

Enrollment: 41 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

3. 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.

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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41 participants in 1 patient group

Standard protocol plus chlorpromazine (CPZ)

Experimental group

Description:

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)

Treatment:

Drug: Chlorpromazine Pill