What is the mechanism of action of this treatment?

Acetazolamide (ACZ) and Temozolomide (TMZ) are common treatments for brain tumors with distinct mechanisms of action. ACZ is a carbonic anhydrase inhibitor that reduces intracranial pressure, potentially alleviating symptoms caused by increased pressure within the skull. It may also enhance the efficacy of TMZ. TMZ is an alkylating agent that damages the DNA of cancer cells by adding alkyl groups, leading to cell death. This DNA damage is crucial for slowing tumor growth and improving outcomes for brain tumor patients.

What side effects are associated with this type of intervention?

Temozolomide (TMZ) is commonly associated with side effects such as nausea, vomiting, fatigue, constipation, and myelosuppression, which can lead to conditions like thrombocytopenia and neutropenia. Patients may also experience headaches and an increased risk of infections due to immunosuppression. Acetazolamide (ACZ), used to reduce intracranial pressure, can cause side effects including tingling in the extremities, altered taste, frequent urination, and electrolyte imbalances. When combined, these treatments may enhance each other's efficacy but also compound some of these side effects, necessitating careful monitoring by healthcare providers.

What prior FDA approvals exist?

Temozolomide (TMZ) is an FDA-approved alkylating agent used in the treatment of glioblastoma multiforme, often in combination with radiation therapy. Another FDA-approved treatment is Carmustine, an alkylating agent available in wafer form (Gliadel) for direct application to the surgical cavity after tumor resection. Bevacizumab, an anti-angiogenic drug, is also approved for recurrent glioblastoma. These treatments aim to damage the DNA of cancer cells or inhibit tumor blood supply, similar to the mechanisms being studied with the combination of Acetazolamide and Temozolomide.

What other types of research exist?

Promising novel alternatives for brain tumor treatment in 2024 include: 1) Carmustine wafers (Gliadel) combined with radiochemotherapy, which have shown long-term efficacy in high-grade gliomas. 2) Trastuzumab Deruxtecan, particularly for HER2-positive brain metastases, as it has demonstrated significant antitumor activity. 3) Proton therapy, which offers precise radiation delivery with reduced damage to surrounding tissues. 4) Immune checkpoint inhibitors, such as pembrolizumab, which are being explored for their potential to enhance the immune response against brain tumors. These alternatives represent cutting-edge approaches that may offer improved outcomes for brain tumor patients.

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Alkylating Agent

Acetazolamide + Temozolomide for Brain Cancer

Phase 1

Recruiting

Led By Bakhtiar Yamini, MD

Research Sponsored by University of Chicago

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients with prior low grade astrocytoma and subsequent histological evidence of grade III or IV tumor

Histologically proven, newly diagnosed IDH wildtype glioblastoma (GBM) with a methylated MGMT promoter

Must not have

Active systemic infection requiring treatment including HIV infection or toxoplasmosis

Severe acute or chronic medical or psychiatric condition, or laboratory abnormality increasing risk associated with study participation or study drug administration

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through study completion an average of one year

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of two drugs, acetazolamide and temozolomide, in patients with a severe type of brain tumor. The goal is to see if this combination can improve treatment outcomes by attacking cancer cells and reducing brain pressure. Temozolomide is a drug with a good safety profile and has been effective in treating this type of brain tumor.

Who is the study for?

Adults with a specific type of brain tumor called malignant astrocytoma, who have not yet started or are undergoing standard treatment with Temozolomide after radiation. They must be in good enough health to participate, able to understand and sign consent, and women must not be pregnant.

What is being tested?

This study tests the combination of Acetazolamide (ACZ) with Temozolomide (TMZ) for treating malignant astrocytoma. It aims to find out what doses are safe without causing too many side effects. Patients will take ACZ daily alongside their regular TMZ treatment for cycles lasting 21 days.

What are the potential side effects?

Possible side effects include those related to Acetazolamide such as allergic reactions if sensitive to sulfa drugs, blood disorders from both medications, and general symptoms like fatigue or digestive issues.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My low grade brain tumor has progressed to a more aggressive form.

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My glioblastoma is IDH wildtype with a methylated MGMT promoter.

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I am currently on a standard treatment plan that includes TMZ after having TMZ and radiation.

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I can care for myself but may need occasional help.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am currently being treated for an active infection, including HIV or toxoplasmosis.

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I do not have any severe health or mental conditions that could make this study risky for me.

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I haven't had cancer, except for non-serious skin cancer or cervical pre-cancer, in the last 3 years.

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I am taking more than 8 mg of dexamethasone daily.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ end of study enrollment period (approximately 6 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~end of study enrollment period (approximately 6 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and end of study enrollment period (approximately 6 years) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of participants with adverse events

Secondary study objectives

Analysis of formalin fixed paraffin embedded surgical specimens.

Measure objective response rate (ORR); change in tumor size

To determine feasibility of cooperative interaction between multiple sites

Side effects data

From 2022 Phase 4 trial • 11 Patients • NCT03377049

External Ventricular Drainage infection

Hydrocephalus

Pulmonary edema

Cardiomyopathy

100%

80%

60%

40%

20%

Study treatment Arm

Acetazolamide Challenge

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Acetazolamide with TemozolomideExperimental Treatment2 Interventions

Subjects will receive daily ACZ together with TMZ in 28 day cycles for up to 6 cycles if they do not experience either disease worsening or unacceptable side effects.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Acetazolamide

2011

Completed Phase 4

~3030

Temozolomide

2010

Completed Phase 3

~1880

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Acetazolamide (ACZ) and Temozolomide (TMZ) are common treatments for brain tumors with distinct mechanisms of action. ACZ is a carbonic anhydrase inhibitor that reduces intracranial pressure, potentially alleviating symptoms caused by increased pressure within the skull. It may also enhance the efficacy of TMZ. TMZ is an alkylating agent that damages the DNA of cancer cells by adding alkyl groups, leading to cell death. This DNA damage is crucial for slowing tumor growth and improving outcomes for brain tumor patients.

Combined intracranial Acriflavine, temozolomide and radiation extends survival in a rat glioma model.