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RACTAC: Repurposing Chlorpromazine in the Treatment of Glioblastoma

Sponsor
Marco G Paggi, MD, PhD (Other)
Overall Status
Recruiting
CT.gov ID
NCT04224441
Collaborator
Regina Elena Cancer Institute (Other), Carlo Besta Neurological Institute (Other), Istituto Oncologico Veneto IRCCS (Other)
41
Enrollment
3
Locations
1
Arm
36
Anticipated Duration (Months)
13.7
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
  • Drug: Chlorpromazine Pill
 Phase 2

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
Anticipated Enrollment :
41 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
Addition of chlorpromazine to the standard GBM treatment during the adjuvant phase of the therapeutic protocol in un-methylated GBM patientsAddition of chlorpromazine to the standard GBM treatment during the adjuvant phase of the therapeutic protocol in un-methylated GBM patients
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Repurposing the Antipsychotic Drug Chlorpromazine as a Therapeutic Agent in the Combined Treatment of Newly Diagnosed Glioblastoma Multiforme
Actual Study Start Date :
Dec 15, 2019
Anticipated Primary Completion Date :
Jun 15, 2022
Anticipated Study Completion Date :
Dec 15, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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)

Drug: Chlorpromazine 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
Other Names:
  • Temozolomide

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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

    2. Progression-free survival (PFS) [6 months]

      Effect of of adding CPZ to the standard GBM therapy, when compared with the standard therapy alone

    Secondary Outcome Measures

    1. 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

    2. Overall survival (OS) [6 months]

      Effect of of adding CPZ to the standard glioblastoma multiforme (GBM) therapy, when compared with the standard therapy alone

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts 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 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

    1. 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.

    2. 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.

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Regina Elena Cancer Institute Roma Lazio Italy 00144
    2 Carlo Besta Neurological Institute Milano Lombardia Italy 20133
    3 Istituto Oncologico Veneto Padova Veneto Italy 35128

    Sponsors and Collaborators

    • Marco G Paggi, MD, PhD
    • Regina Elena Cancer Institute
    • Carlo Besta Neurological Institute
    • Istituto Oncologico Veneto IRCCS

    Investigators

    • Principal Investigator: Marco G Paggi, MD, PhD, Regina Elena Cancer Institute

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Marco G Paggi, MD, PhD, Medical Doctor, Clinical Pharmacologist, Regina Elena Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT04224441
    Other Study ID Numbers:
    • 2019-001988-75
    First Posted:
    Jan 13, 2020
    Last Update Posted:
    Jan 13, 2020
    Last Verified:
    Jan 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Marco G Paggi, MD, PhD, Medical Doctor, Clinical Pharmacologist, Regina Elena Cancer Institute
    drug repurposing
    antipsychotic drugs
    glioblastoma
    Additional relevant MeSH terms:
    Glioblastoma
    Temozolomide
    Chlorpromazine

    Study Results

    No Results Posted as of Jan 13, 2020