Acetazolamide + Temozolomide for Brain Cancer

Overseen By Bakhtiar Yamini, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Chicago

Must be taking: Temozolomide

Must not be taking: Corticosteroids

Disqualifiers: Invasive malignancy, Infection, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, acetazolamide (ACZ) and temozolomide (TMZ), to assess their safety for people with a specific type of aggressive brain cancer called astrocytoma. The focus is on patients with newly diagnosed, high-grade astrocytoma with a certain genetic marker (MGMT methylation) who plan to use temozolomide as part of their treatment after initial therapies. Participants will take both drugs in cycles to monitor for any serious side effects. This trial suits those recently diagnosed with this type of brain cancer and already using temozolomide as part of their ongoing treatment. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroid therapy, you must not exceed 8 mg of dexamethasone daily at the time of enrollment.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that combining acetazolamide (ACZ) with temozolomide (TMZ) is safe and manageable for people with brain cancer. Studies on patients with glioblastoma, a type of brain tumor, have found that adding acetazolamide to the usual temozolomide treatment does not cause major safety issues. Temozolomide is generally well tolerated, though some people might experience fatigue, nausea, or low blood cell counts. In rare cases, serious blood-related side effects can occur. Overall, this drug combination has demonstrated a promising safety record in previous studies with similar patient groups. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about combining Acetazolamide with Temozolomide for brain cancer because this approach introduces a new mechanism to enhance the effectiveness of Temozolomide, a standard treatment. Acetazolamide, typically used to treat glaucoma and high-altitude sickness, may help Temozolomide penetrate the brain more effectively by reducing fluid pressure and altering the tumor's environment. This combination has the potential to improve treatment outcomes for patients by targeting the cancer more directly and efficiently, addressing a major challenge with current therapies.

What evidence suggests that this treatment might be an effective treatment for brain cancer?

Research has shown that using acetazolamide with temozolomide, the combination tested in this trial, may help treat brain cancer. Studies have found that acetazolamide is safe and might be effective for challenging brain tumors like glioblastoma. In one study, patients with severe tumors lived for an average of 30.1 months, surpassing typical outcomes. This combination is generally well-tolerated, with safety being a key finding in early research. While temozolomide alone hasn't consistently improved survival rates, adding acetazolamide could offer new hope. ^{1 2 3 4 5}

Who Is on the Research Team?

Bakhtiar Yamini, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

My glioblastoma is IDH wildtype with a methylated MGMT promoter.

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

Exclusion Criteria

Pregnancy confirmed by positive serum beta-hCG laboratory test, Breast-feeding

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

Hypersensitivity to acetazolamide or sulfonamides

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily oral acetazolamide with temozolomide in 28-day cycles for up to 6 cycles

6 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may continue treatment if they do not experience disease worsening or unacceptable side effects

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Acetazolamide
• Temozolomide

Trial Overview 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.

How Is the Trial Designed?

Group I: Acetazolamide with Temozolomide Experimental Treatment 2 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.

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

Approved in European Union as Temodal for:

• Newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and subsequently as monotherapy treatment
• Children from the age of three years, adolescents and adults with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy

Approved in United States as Temodar for:

• Newly diagnosed glioblastoma concomitantly with radiotherapy and subsequently as monotherapy treatment
• Newly diagnosed or refractory anaplastic astrocytoma

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

In a randomized trial involving 447 patients with recurrent high-grade glioma, temozolomide (TMZ) did not show a clear survival advantage over procarbazine, lomustine, and vincristine (PCV), with a hazard ratio of 0.91, indicating similar effectiveness.

However, within the TMZ treatment groups, the 5-day regimen demonstrated better overall progression-free survival and quality of life compared to the 21-day regimen, suggesting that shorter treatment schedules may be more effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide versus procarbazine, lomustine, and vincristine in recurrent high-grade glioma. Brada, M., Stenning, S., Gabe, R., et al.[2022]

In a phase II trial involving 46 patients with progressive low-grade glioma, Temozolomide (Temodar) demonstrated a 61% objective response rate, with 24% achieving complete response and 37% achieving partial response.

The treatment showed promising safety, with limited toxicity observed; however, one patient experienced severe complications, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of temozolomide in patients with progressive low-grade glioma. Quinn, JA., Reardon, DA., Friedman, AH., et al.[2022]

The study confirmed that the generic temozolomide capsules (TOZ039) are bioequivalent to the brand Temodal® capsules, with pharmacokinetic parameters falling within the acceptable range for both 20-mg and 100-mg doses in 29 patients with brain tumors.

The treatment was found to be safe, with no treatment-related severe adverse events or mortality reported, although 82.8% of patients experienced some adverse effects, highlighting the importance of monitoring patient responses during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence study of 20-mg and 100-mg temozolomide capsules (TOZ309 and Temodal®) in glioma patients in China. Hu, C., Lin, Q., Liu, C., et al.[2021]

Temozolomide (TMZ) is shown to be more cost-effective than the traditional PCV treatment for glioblastoma multiforme (GBM), with costs of €2367 per extra life-month and €32,471 per quality-adjusted life-year (QALY).

The analysis indicates that TMZ has a high probability (over 60%) of being the most cost-effective treatment option at various willingness-to-pay thresholds, especially when considering quality of life improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic evaluation of temozolomide in the treatment of recurrent glioblastoma multiforme. Martikainen, JA., Kivioja, A., Hallinen, T., et al.[2018]

Temozolomide (TMZ) is an effective oral treatment for malignant gliomas, providing significant survival benefits while being generally well tolerated by patients.

While most side effects of TMZ are mild to moderate, there is a risk of severe hematologic adverse events, such as myelodysplastic syndrome and aplastic anemia, which have been documented in the literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-related hematologic toxicity. Scaringi, C., De Sanctis, V., Minniti, G., et al.[2018]

Temozolomide (TMZ) is generally safe with mild to moderate side effects, but this case report highlights a rare instance of severe aplastic anemia (AA) in a 68-year-old female patient following treatment for glioblastoma, indicating a potential serious risk associated with the drug.

The patient's AA was managed successfully with supportive care, including platelet transfusions and growth factor treatment, and her blood counts returned to normal within 38 days, emphasizing the importance of monitoring blood parameters during and after TMZ treatment to detect such rare toxicities early.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-induced aplastic anaemia: Case report and review of the literature. Gilbar, PJ., Pokharel, K., Mangos, HM.[2022]

Temozolomide is primarily used for treating refractory central nervous system cancers like anaplastic astrocytoma and glioblastoma, but ongoing clinical trials are exploring its efficacy and safety in newly diagnosed gliomas and other types of tumors.

Research is also investigating different dosing schedules and combinations with other treatments, suggesting that temozolomide could be a versatile option in cancer therapy beyond its current approved uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions for temozolomide therapy. Yung, WK.[2019]

In a study involving 831 patients across 21 French hospitals, temozolomide (TMZ) prescriptions were found to conform to the French summary of product characteristics (SPC) in 51.9% of cases, indicating a moderate level of adherence to official guidelines.

The study revealed high conformity (91.5%) to the prescription guidebook, with specific adherence rates of 62% for newly diagnosed glioblastoma patients receiving combined treatment with radiotherapy, 72% for maintenance therapy, and 66% for patients with progressive disease, highlighting the overall compliance in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter prospective observational study of the conformity of temozolomide prescriptions in France. Tilleul, P., Brignone, M., Hassani, Y., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10901541/

A multi-institutional phase I study of acetazolamide with ... Conclusions. The addition of acetazolamide is safe and tolerable in GBM patients receiving standard TMZ. Survival results compare favorably to historical data ...

2. ajmc.com ajmc.com/view/study-finds-acetazolamide-may-be-effective-in-treating-glioblastoma

Study Finds Acetazolamide May Be Effective in Treating ... According to a new study, acetazolamide may also be effective in treating the fast-growing brain tumor glioblastoma.

3. withpower.com withpower.com/trial/phase-1-glioma-9-2018-f215f

Acetazolamide + Temozolomide for Brain Cancer In a randomized trial involving 447 patients with recurrent high-grade glioma, temozolomide (TMZ) did not show a clear survival advantage over procarbazine, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03011671

Study of Acetazolamide With Temozolomide in Adults ... To determine the safety, tolerability and adverse event profile of adding acetazolamide to temozolomide in patients with newly diagnosed malignant astrocytoma.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38420615/

A multi-institutional phase I study of acetazolamide with ... In the 23 WHO Grade 4 patients, the median overall survival (OS) was 30.1 months and the median progression-free survival was 16.0 months. The ...