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Repurposing Chlorpromazine in the Treatment of Glioblastoma (RACTAC)

Primary Purpose

Glioblastoma Multiforme, MGMT-Unmethylated Glioblastoma

Status

Unknown status

Phase

Phase 2

Locations

Italy

Study Type

Interventional

Intervention

Chlorpromazine Pill

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring drug repurposing, antipsychotic drugs, glioblastoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

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.

Sites / Locations

Regina Elena Cancer InstituteRecruiting
Carlo Besta Neurological InstituteRecruiting
Istituto Oncologico VenetoRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Standard protocol plus chlorpromazine (CPZ)

Arm 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)

Outcomes

Primary Outcome Measures

Evaluation of toxicity

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)

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

Secondary Outcome Measures

Evaluation of tumor response

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

Overall survival (OS)

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

Full Information

NCT ID

NCT04224441

First Posted

January 7, 2020

Last Updated

January 9, 2020

Sponsor

Marco G Paggi, MD, PhD

Collaborators

Regina Elena Cancer Institute, Carlo Besta Neurological Institute, Istituto Oncologico Veneto IRCCS

1. Study Identification

Unique Protocol Identification Number

NCT04224441

Brief Title

Repurposing Chlorpromazine in the Treatment of Glioblastoma

Acronym

RACTAC

Official Title

Repurposing the Antipsychotic Drug Chlorpromazine as a Therapeutic Agent in the Combined Treatment of Newly Diagnosed Glioblastoma Multiforme

Study Type

Interventional

2. Study Status

Record Verification Date

January 2020

Overall Recruitment Status

Unknown status

Study Start Date

December 15, 2019 (Actual)

Primary Completion Date

June 15, 2022 (Anticipated)

Study Completion Date

December 15, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Marco G Paggi, MD, PhD

Collaborators

Regina Elena Cancer Institute, Carlo Besta Neurological Institute, Istituto Oncologico Veneto IRCCS

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. 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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma Multiforme, MGMT-Unmethylated Glioblastoma

Keywords

drug repurposing, antipsychotic drugs, glioblastoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

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)

Allocation

N/A

Enrollment

41 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Standard protocol plus chlorpromazine (CPZ)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Chlorpromazine Pill

Other Intervention Name(s)

Temozolomide

Intervention Description

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

Primary Outcome Measure Information:

Title

Evaluation of toxicity

Description

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

Time Frame

6 months

Title

Progression-free survival (PFS)

Description

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

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Evaluation of tumor response

Description

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

Time Frame

6 months

Title

Overall survival (OS)

Description

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

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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. 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Andrea Pace, MD

Phone

+39 06 52666975

andrea.pace@ifo.gov.it

First Name & Middle Initial & Last Name or Official Title & Degree

Diana Giannarelli, PhD

Phone

+39 06 52665607

diana.giannarelli@ifo.gov.it

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marco G Paggi, MD, PhD

Organizational Affiliation

Regina Elena Cancer Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Regina Elena Cancer Institute

City

Roma

State/Province

Lazio

ZIP/Postal Code

00144

Country

Italy

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Andrea Pace, MD

Phone

+39 06 52666975

andrea.pace@ifo.gov.it

First Name & Middle Initial & Last Name & Degree

Diana Giannarelli, PhD

Phone

+39 06 52665607

diana.giannarelli@ifo.gov.it

Facility Name

Carlo Besta Neurological Institute

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20133

Country

Italy

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Antonio Silvani, MD

antonio.silvani@istituto-besta.it

Facility Name

Istituto Oncologico Veneto

City

Padova

State/Province

Veneto

ZIP/Postal Code

35128

Country

Italy

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Giuseppe Lombardi, MD

giuseppe.lombardi@iov.veneto.it

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

De-identified patient data describing primary and secondary outcomes will be made available

IPD Sharing Time Frame

Data will be available after 6 months after study completion

IPD Sharing Access Criteria

Upon request. A valid Uniform Resource Locator (URL) will be reported

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Repurposing Chlorpromazine in the Treatment of Glioblastoma

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