Chlorpromazine and Standard of Care for Glioblastoma

Overseen By Varun Monga, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Varun Monga, MD

Must not be taking: Investigational agents

Disqualifiers: Recurrent glioma, CNS disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Who Is on the Research Team?

Mohammed Milhem, MBBS

Principal Investigator

University of Iowa Hospitals and Clinics Holden Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed glioblastoma who have had recent surgery. They must be in a stable condition (ECOG 0-2), with good blood counts and liver function, and able to give informed consent. Excluded are those with heart issues, prior high-grade glioma treatments, other CNS diseases or malignancies that could affect the study, uncontrolled illnesses, or pregnant/breastfeeding women.

Inclusion Criteria

Plasma blood chemistries within 21 days of radiation fraction 1, as defined below:

My diagnosis was confirmed through a surgical procedure.

My treatment will start within 5 weeks after my last surgery.

Exclusion Criteria

I have had radiation therapy to my head or neck before.

I am allergic to medications similar to temozolomide or chlorpromazine.

I am not on any experimental drugs but may be using TTF as part of my standard care.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

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)

8 weeks

Weekly visits for radiation and monitoring

Interim Phase

Continue oral chlorpromazine daily dose post-radiation and prior to beginning adjuvant temozolomide

4 weeks

Adjuvant Phase

Start oral temozolomide once daily for 5 consecutive days of a 28 day cycle, and continue oral daily chlorpromazine. Treatment will continue for up to 6 cycles.

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Chlorpromazine
• Radiation Therapy
• Temozolomide

Trial Overview The study tests chlorpromazine combined with temozolomide and radiation therapy as a new treatment approach for glioblastoma multiforme. It's an early-phase trial to see if this repurposed drug can work well alongside standard cancer treatments.

How Is the Trial Designed?

Group I: Chlorpromazine with standard of care chemoradiation Experimental Treatment 3 Interventions

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.

Chlorpromazine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Thorazine for:

• Schizophrenia
• Nausea and vomiting
• Hiccups
• Acute intermittent porphyria
• Tetanus
• Severe behavioral problems in children

Approved in European Union as Largactil for:

• Schizophrenia and other psychoses
• Nausea and vomiting
• Hiccups
• Acute intermittent porphyria
• Tetanus

Approved in Canada as Chlorpromazine Hydrochloride for:

• Schizophrenia and other psychoses
• Nausea and vomiting
• Hiccups
• Acute intermittent porphyria
• Tetanus

Who Is Running the Clinical Trial?

Varun Monga, MD

Lead Sponsor

Trials

7

Recruited

130+

Mohammed Milhem

Lead Sponsor

Trials

9

Recruited

240+