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Repurposing Chlorpromazine in the Treatment of Glioblastoma (RACTAC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04224441
Recruitment Status : Recruiting
First Posted : January 13, 2020
Last Update Posted : January 13, 2020
Sponsor:
Collaborators:
Regina Elena Cancer Institute
Carlo Besta Neurological Institute
Istituto Oncologico Veneto IRCCS
Information provided by (Responsible Party):
Marco G Paggi, MD, PhD, Regina Elena Cancer Institute

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
Glioblastoma Multiforme MGMT-Unmethylated Glioblastoma 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 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 : December 15, 2019
Estimated Primary Completion Date : June 15, 2022
Estimated Study Completion Date : December 15, 2022


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 Name: Temozolomide




Primary Outcome Measures :
  1. 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

  2. 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 Outcome Measures :
  1. Evaluation of tumor response [ Time Frame: 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) [ Time Frame: 6 months ]
    Effect of of adding CPZ to the standard glioblastoma multiforme (GBM) therapy, when compared with the standard therapy alone



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04224441


Contacts
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Contact: Andrea Pace, MD +39 06 52666975 andrea.pace@ifo.gov.it
Contact: Diana Giannarelli, PhD +39 06 52665607 diana.giannarelli@ifo.gov.it

Locations
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Italy
Regina Elena Cancer Institute Recruiting
Roma, Lazio, Italy, 00144
Contact: Andrea Pace, MD    +39 06 52666975    andrea.pace@ifo.gov.it   
Contact: Diana Giannarelli, PhD    +39 06 52665607    diana.giannarelli@ifo.gov.it   
Carlo Besta Neurological Institute Recruiting
Milano, Lombardia, Italy, 20133
Contact: Antonio Silvani, MD       antonio.silvani@istituto-besta.it   
Istituto Oncologico Veneto Recruiting
Padova, Veneto, Italy, 35128
Contact: Giuseppe Lombardi, MD       giuseppe.lombardi@iov.veneto.it   
Sponsors and Collaborators
Marco G Paggi, MD, PhD
Regina Elena Cancer Institute
Carlo Besta Neurological Institute
Istituto Oncologico Veneto IRCCS
Investigators
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Principal Investigator: Marco G Paggi, MD, PhD Regina Elena Cancer Institute
Publications:

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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: January 13, 2020    Key Record Dates
Last Update Posted: January 13, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified patient data describing primary and secondary outcomes will be made available
Supporting Materials: Study Protocol
Clinical Study Report (CSR)
Time Frame: Data will be available after 6 months after study completion
Access Criteria: Upon request. A valid Uniform Resource Locator (URL) will be reported

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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, Regina Elena Cancer Institute:
drug repurposing
antipsychotic drugs
glioblastoma
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Chlorpromazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents