Glioblastoma MultiformePhase 1NCT05190315
Chlorpromazine and Standard of Care in Glioblastoma
A Phase 1 study testing Chlorpromazine, Temozolomide and Radiation Therapy in people with Glioblastoma Multiforme, run by Mohammed Milhem at 1 site in United States.
Trial summary
This is a phase 1 study investigating the re-purposing of chlorpromazine, combined with temozolomide and radiation in the treatment of newly diagnosed glioblastoma multiforme. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- Chlorpromazine, Temozolomide and Radiation Therapy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Jan 2022to 28 Jul 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have newly diagnosed (i.e., within 5 weeks from recent surgery), histologically or cytologically or molecularly confirmed glioblastoma, gliosarcoma, or diffuse midline glioma.
- Diagnosis must be made by surgical biopsy or excision.
- Therapy must begin ≤ 5 weeks after most recent surgery.
- Age ≥ 18 years
- ECOG performance status 0-2 (Karnofsky > 50%, see Appendix B).
- A complete blood count and differential must be obtained within 21 days prior to radiation fraction 1, with adequate bone marrow functions as defined below:
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- Absolute neutrophil count (ANC) ≥ 1500 cells per mm^3
- Platelets ≥ 100,000 per mm^3
- Hemoglobin ≥ 8 g/dL
- Plasma blood chemistries within 21 days of radiation fraction 1, as defined below:
- Creatinine ≤ 2.0 mg/dL
- Total bilirubin ≤ 1.5 mg/dL
- ALT ≤ 3 times the institutional upper limit of normal
- AST ≤ 3 times the institutional upper limit of normal
- Patient or patient's legally authorized representative's ability to understand and willingness to sign a written informed consent document.
Who cannot join
- Recurrent high-grade glioma.
- Significant abnormalities on ECG at screening. QTcF > 450 msec for males or > 470 msec for females at screening.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or chlorpromazine.
- Significant co-morbid central nervous system disease, including but not limited to, multiple sclerosis, Parkinson's disease, history of myasthenia gravis, or dementia.
- Patients with prior malignancies of the same or different tumor type and patients with concurrent malignancies of the same or different tumor type whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational drug.
- Patients who have received prior chemotherapy (including Gliadel wafers) for the current glioma
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- Prior radiation therapy to the head or neck, which would result in overlap of radiation therapy fields.
- Patients may not be receiving any other investigational agents. Use of tumor treating fields (TTF) in adjuvant phase is permitted as per standard of care.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, hypoparathyroidism, or psychiatric illness/social situations that would limit compliance with study requirements. Uncontrolled seizures despite being on maximal anti-seizure therapy.
- Pregnant women are excluded from this study because ionizing radiation is a known teratogen, and temozolomide is a Class D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with temozolomide, breastfeeding should be discontinued if the mother is treated with temozolomide.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242
About this study
Official title: A Phase I Trial of Chlorpromazine Together With Standard of Care in New Diagnosis of Glioblastoma
This is a phase 1 study investigating the re-purposing of chlorpromazine, combined with temozolomide and radiation in the treatment of newly diagnosed glioblastoma multiforme.
Read the detailed description
The purpose of the study is to determine the safety and acute toxicity of chlorpromazine (CPZ) when administered throughout the standard treatment protocol for glioblastoma multiforme, as well as determine progression free survival.
Chlorpromazine (25 mg daily for the first 3 patients then dose escalate to 50 mg if no DLT) will be added to a standard of care regimen which includes radiation and adjuvant Temozolomide. Chlorpromazine treatment will continue for up to 6 cycles or until criteria for removal is met. Temozolomide is administered following standard practice adopted at the University of Iowa Hospitals and Clinics (UIHC).
Subject will have several MRI scans for disease assessment throughout the treatment. There will be 3 phases of treatment for each patient:
Concomitant Chlorpromazine- Start 7 days prior to day 1 of concurrent Temozolomide and radiation. Will continue with Chlorpromazine through radiation therapy (temozolomide will cease after 49 days)
Interim Phase- When radiation has ended, subject will take Chlorpromazine for 28 days- no Temozolomide
Adjuvant phase- subject resumes Temozolomide per standard practice, and continues to take Chlorpromazine through 6 cycles of Temozolomide.
- Conditions
- Glioblastoma Multiforme
- Being tested
- Chlorpromazine, Temozolomide, Radiation Therapy
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChlorpromazineDrug
Also called Thorazine
Concurrent Phase: Oral chlorpromazine at 25 mg daily for the first 3 patients, then dose escalate to 50 mg if no dose limiting toxicity (DLT). Starting 7 days prior to radiation start.
Interim Phase: Chlorpromazine, 25 mg per day for first 3 subjects and then dose escalate to 50 mg per day if no DLT, will continue post radiation and prior to beginning adjuvant temozolomide.
Adjuvant Phase: Chlorpromazine, 25 mg per day for first 3 subjects and then dose escalate to 50 mg per day if no DLT, will be continued daily (7 days per week) concomitant with Temozolomide.
TemozolomideDrug
Also called Temodar
Concurrent Phase: Oral temozolomide at 75 mg/m2 per day concomitant with focal radiation and chlorpromazine. Temozolomide should be started on day 1 of radiation therapy, either at bedtime or morning as per patient preference.
Adjuvant Phase: Oral Temozolomide concomitant with Chlorpromazine, starting Temozolomide dose (Cycle 1) is 150 mg/m2 daily with a single dose escalation to 200 mg/m2 daily in subsequent cycles if no treatment-related adverse events > grade 2 are noted. Temozolomide to be taken once daily for 5 consecutive days (1-5) of a 28 day cycle.
Radiation TherapyRadiation
Concurrent Phase: Radiation therapy administered daily, M-F, to a total dose of 60 Gy in 2 Gy Fractions for a total of 30 fractions.
| Study group | Role | What they receive |
|---|---|---|
| Chlorpromazine with standard of care chemoradiation | Experimental | Each patient will undergo 3 phases of treatment.
Concurrent Phase: includes concurrent radiation Monday - Friday (60 Gy total radiation dose in 2 Gy fractions), oral temozolomide (75 mg/m2/day) daily for a maximum 49 days starting Day 1 of radiation, and oral chlorpromazine (25 mg for first 3 patients, then escalate to 50 mg if no DLT) daily starting 7 days prior to radiation start.
Interim Phase: Continue oral chlorpromazine daily dose post-radiation and prior to beginning adjuvant temozolomide.
Adjuvant Phase: 28 days after radiation fini (+/- 5 business days), Start oral temozolomide (starting dose 150 mg/m2/day and escalated to 200 mg/m2/day if no treatment related adverse events noted) once daily for 5 consecutive days of a 28 day cycle, and continue oral daily chlorpromazine seven days a week per cycle. The adjuvant phase treatment will continue for up to 6 cycles. Cycle length is 28 days. Receives: Drug: Chlorpromazine; Drug: Temozolomide; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and acute toxicity of chlorpromazine (CPZ) when administered throughout the standard treatment for glioblastoma multiforme (GBM) will be graded per NCI's Common Terminology Criteria for Adverse Events v 5.0 (CTCAE v5.0)
The incidence of treatment-emergent adverse events will be summarized by system organ class and/or preferred term, type of adverse event, and severity (based on NCI CTCAE v5.0 grades)
Measured: First treatment through 30 days post last dose of study drug
Recommended phase II dose of chlorpromazine in combination with the standard treatment protocol for glioblastoma
The study will utilize a 3+3 design, and up to 6 patients will be treated at each dose level. The recommended Phase II dose will be defined as the highest dose level for which at most 1 of 6 patients experience a dose limiting toxicity (DLT).
Measured: 4 weeks
Secondary outcomes (2)
Progression free survival of patients with newly diagnosed GBM treated with CPZ and standard chemoradiation 6 months from the date of surgery
Time from diagnosis to documented disease progression or death due to any cause.
Measured: 2 years
2-year overall survival of patients with newly diagnosed GBM treated with CPZ and standard chemoradiation 6 months from the date of surgery
Time from diagnosis up to 2 years post completion of treatment
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2022
- Study start28 Jan 2022
- Primary completion25 Apr 2023
- Study completion28 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mohammed Milhem
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Mohammed Milhem, University of Iowa
- Investigators
- Mohammed Milhem, MBBS, Principal investigator, University of Iowa Hospitals and Clinics Holden Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05190315
- Sponsor's protocol ID
- 202109340
- Status last verified
- Aug 2025
- First submitted
- 30 Dec 2021
- Last updated
- 2 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Chlorpromazine Together With Standard of Care in New Diagnosis of Glioblastoma
- ClinicalTrials.gov ID
- NCT05190315
- Acronym / sponsor ID
- 202109340
- Conditions
- Glioblastoma Multiforme
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Mohammed MilhemUniversity, hospital or other
- Study start
- 28 Jan 2022 (actual)
- Primary completion
- 25 Apr 2023 (actual)
- Study completion
- 28 Jul 2024 (actual)
- First posted
- 13 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 1 study investigating the re-purposing of chlorpromazine, combined with temozolomide and radiation in the treatment of newly diagnosed glioblastoma multiforme.
Detailed description
The purpose of the study is to determine the safety and acute toxicity of chlorpromazine (CPZ) when administered throughout the standard treatment protocol for glioblastoma multiforme, as well as determine progression free survival.
Chlorpromazine (25 mg daily for the first 3 patients then dose escalate to 50 mg if no DLT) will be added to a standard of care regimen which includes radiation and adjuvant Temozolomide. Chlorpromazine treatment will continue for up to 6 cycles or until criteria for removal is met. Temozolomide is administered following standard practice adopted at the University of Iowa Hospitals and Clinics (UIHC).
Subject will have several MRI scans for disease assessment throughout the treatment. There will be 3 phases of treatment for each patient:
Concomitant Chlorpromazine- Start 7 days prior to day 1 of concurrent Temozolomide and radiation. Will continue with Chlorpromazine through radiation therapy (temozolomide will cease after 49 days)
Interim Phase- When radiation has ended, subject will take Chlorpromazine for 28 days- no Temozolomide
Adjuvant phase- subject resumes Temozolomide per standard practice, and continues to take Chlorpromazine through 6 cycles of Temozolomide.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chlorpromazine with standard of care chemoradiation | Experimental | Drug: Chlorpromazine, Drug: Temozolomide, Radiation: Radiation TherapyEach patient will undergo 3 phases of treatment. Concurrent Phase: includes concurrent radiation Monday - Friday (60 Gy total radiation dose in 2 Gy fractions), oral temozolomide (75 mg/m2/day) daily for a maximum 49 days starting Day 1 of radiation, and oral chlorpromazine (25 mg for first 3 patients, then escalate to 50 mg if no DLT) daily starting 7 days prior to radiation start. Interim Phase: Continue oral chlorpromazine daily dose post-radiation and prior to beginning adjuvant temozolomide. Adjuvant Phase: 28 days after radiation fini (+/- 5 business days), Start oral temozolomide (starting dose 150 mg/m2/day and escalated to 200 mg/m2/day if no treatment related adverse events noted) once daily for 5 consecutive days of a 28 day cycle, and continue oral daily chlorpromazine seven days a week per cycle. The adjuvant phase treatment will continue for up to 6 cycles. Cycle length is 28 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients must have newly diagnosed (i.e., within 5 weeks from recent surgery), histologically or cytologically or molecularly confirmed glioblastoma, gliosarcoma, or diffuse midline glioma.
- Diagnosis must be made by surgical biopsy or excision.
- Therapy must begin ≤ 5 weeks after most recent surgery.
- Age ≥ 18 years
- ECOG performance status 0-2 (Karnofsky > 50%, see Appendix B).
Key exclusion criteria (10 listed)
- Recurrent high-grade glioma.
- Significant abnormalities on ECG at screening. QTcF > 450 msec for males or > 470 msec for females at screening.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or chlorpromazine.
- Significant co-morbid central nervous system disease, including but not limited to, multiple sclerosis, Parkinson's disease, history of myasthenia gravis, or dementia.
- Patients with prior malignancies of the same or different tumor type and patients with concurrent malignancies of the same or different tumor type whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational drug.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ChlorpromazineAlso: ThorazineConcurrent Phase: Oral chlorpromazine at 25 mg daily for the first 3 patients, then dose escalate to 50 mg if no dose limiting toxicity (DLT). Starting 7 days prior to radiation start. Interim Phase: Chlorpromazine, 25 mg per day for first 3 subjects and then dose escalate to 50 mg per day if no DLT, will continue post radiation and prior to beginning adjuvant temozolomide. Adjuvant Phase: Chlorpromazine, 25 mg per day for first 3 subjects and then dose escalate to 50 mg per day if no DLT, will be continued daily (7 days per week) concomitant with Temozolomide. | Drug | Chlorpromazine with standard of care chemoradiation |
| TemozolomideAlso: TemodarConcurrent Phase: Oral temozolomide at 75 mg/m2 per day concomitant with focal radiation and chlorpromazine. Temozolomide should be started on day 1 of radiation therapy, either at bedtime or morning as per patient preference. Adjuvant Phase: Oral Temozolomide concomitant with Chlorpromazine, starting Temozolomide dose (Cycle 1) is 150 mg/m2 daily with a single dose escalation to 200 mg/m2 daily in subsequent cycles if no treatment-related adverse events > grade 2 are noted. Temozolomide to be taken once daily for 5 consecutive days (1-5) of a 28 day cycle. | Drug | Chlorpromazine with standard of care chemoradiation |
| Radiation TherapyConcurrent Phase: Radiation therapy administered daily, M-F, to a total dose of 60 Gy in 2 Gy Fractions for a total of 30 fractions. | Radiation | Chlorpromazine with standard of care chemoradiation |
Primary outcome
Safety and acute toxicity of chlorpromazine (CPZ) when administered throughout the standard treatment for glioblastoma multiforme (GBM) will be graded per NCI's Common Terminology Criteria for Adverse Events v 5.0 (CTCAE v5.0)
Time frame: First treatment through 30 days post last dose of study drug
The incidence of treatment-emergent adverse events will be summarized by system organ class and/or preferred term, type of adverse event, and severity (based on NCI CTCAE v5.0 grades)
Recommended phase II dose of chlorpromazine in combination with the standard treatment protocol for glioblastoma
Time frame: 4 weeks
The study will utilize a 3+3 design, and up to 6 patients will be treated at each dose level. The recommended Phase II dose will be defined as the highest dose level for which at most 1 of 6 patients experience a dose limiting toxicity (DLT).
2 secondary outcomes
Progression free survival of patients with newly diagnosed GBM treated with CPZ and standard chemoradiation 6 months from the date of surgery
Time frame: 2 years
2-year overall survival of patients with newly diagnosed GBM treated with CPZ and standard chemoradiation 6 months from the date of surgery
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mohammed Milhem, MBBS principal investigator
University of Iowa Hospitals and Clinics Holden Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Chlorpromazine, Temozolomide and Radiation Therapy in people with Glioblastoma Multiforme, run by Mohammed Milhem at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and acute toxicity of chlorpromazine (CPZ) when administered throughout the standard treatment for glioblastoma multiforme (GBM) will be graded per NCI's Common Terminology Criteria for Adverse Events v 5.0 (CTCAE v5.0) (time frame: First treatment through 30 days post last dose of study drug). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2025; AzTrials last refreshed its copy on 8 Nov 2026.