The Effectiveness of HP and TMZ Synergism on Adult Recurrence GBM

Clinical Study for Evaluating the Effectiveness of Haloperidol and Temozolomide Synergism on Adult Recurrence Glioblastoma

The study of investigators indicated that TMZ can up-regulate dopamine D2 receptor (DRD2) expression, and mediates Ferroptosis inhibition and chemoresistance of GBM. The clinical data also proved that the DRD2 expression in recurrent GBM is significantly higher than that in primary GBM. Moreover, the DRD2 antagonist haloperidol can attenuate the above function of DRD2, and increase the sensitivity of GBM to the TMZ by inducing fatal autophagy and ferroptosis. In xenograft mice, the combined usage of haloperidol and Temozolomide (TMZ) can significantly inhibit tumor growth and increase overall survival. The investigators' findings have been published in Clinical cancer research. Haloperidol known as a butylbenzene antipsychotic drug, has been widely used in several kinds of mental illnesses, such as depression, schizophrenia, and Bipolar disorder. And the safe dosage of the haloperidol is clear so far. So in this study, the investigators will recruit the patients who suffered from recurrent GBM, and evaluate the effectiveness of single TMZ chemotherapy or combined with haloperidol.

Study Overview

• Status: Not yet recruiting
• Conditions: Glioblastoma Multiforme
• Intervention / Treatment: Drug: Temozolomide; Drug: Haloperidol Tablets

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yuntao Lu, Ph.D; Phone Number: +86013632101002; Email: lllu2000yun@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients
• Primary GBM underwent surgery and TMZ chemoradiotherapy, and MRI confirmed the tumor recurrence
• Without severe cardiac diseases

Exclusion Criteria:

• Child patients (<18 years)
• Recurrence tumors grow fast, which needs surgery removal
• H3K27M midline glioblastoma
• Suffered with severe cardiac diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: TMZ single; Single oral Temozolomide	Drug: Temozolomide; Temozolomide, 150mg/kg, Oral, Once/Day, 5/28 days
Experimental: TMZ and Haloperidol; Oral Temozolomide and Haloperidol	Drug: Temozolomide; Temozolomide, 150mg/kg, Oral, Once/Day, 5/28 days; Drug: Haloperidol Tablets; Haloperidol tablet 6mg, Oral, Triple/Day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of partial relief and complete relief	Detected the percentage of partial relief and complete relief according to RANO criteria.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival was evaluated during follow-up period.	One year
DRD2 expression	If the recurrent GBM underwent surgery resection, the DRD2 expression was detected.	One year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse drug reaction of haloperidol	Detection the adverse drug reaction of haloperidol	One year

Collaborators and Investigators

• Sponsor: Southern Medical University, China
• Investigators: Principal Investigator: Yuntao Lu, Ph.D, Nanfang Hospital, Southern Medical University

Publications and helpful links

General Publications

• Shi L, Chen H, Chen K, Zhong C, Song C, Huang Y, Wang T, Chen L, Li C, Huang A, Qi S, Li H, Lu Y. The DRD2 Antagonist Haloperidol Mediates Autophagy-Induced Ferroptosis to Increase Temozolomide Sensitivity by Promoting Endoplasmic Reticulum Stress in Glioblastoma. Clin Cancer Res. 2023 Aug 15;29(16):3172-3188. doi: 10.1158/1078-0432.CCR-22-3971.

Helpful Links

• Our study about the anti-tumor function of Haloperidol, which was published in Clinical Cancer research.

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: January 11, 2024
• First Submitted That Met QC Criteria: January 22, 2024
• First Posted (Actual): January 23, 2024

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Autophagy; Haloperidol; Chemoresistance; Ferropotosis; DRD2
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Dopamine Antagonists; Anti-Dyskinesia Agents; Temozolomide; Haloperidol; Haloperidol decanoate
• Other Study ID Numbers: SEC-DRD2

Drug and device information, study documents

• 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