Study of Acetazolamide With Temozolomide in Adults With Newly Diagnosed or Recurrent Malignant Glioma

NCT03011671 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IRB16-0767
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I study that examines the rate of dose limiting side effects in patients with malignant astrocytoma treated with combination acetazolamide (ACZ) and temozolomide (TMZ). Eligible patients must have histologically proven newly diagnosed, O6-methylguanine-DNA methyltransferase (MGMT) methylated WHO grade III or IV astrocytoma and be planning to undergo treatment with standard adjuvant TMZ (after completing treatment with TMZ and ionizing radiation (IR)). During this study, patients will receive daily oral ACZ with TMZ. During each cycle, ACZ will be started on the day of TMZ initiation and continued for a total of 21 days.

Conditions

Malignant Glioma of Brain

Keywords

Malignant Glioma of Brain; Acetazolamide; Temozolomide

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events

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

  28 Days

Secondary Outcomes (5)

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

  6 months

• Time until progression free survival (PFS)

  6 months

• Time until overall survival (OS)

  From start date of therapy to the date of death from any cause, whichever may come first, assessed up to 100 months

• Analysis of formalin fixed paraffin embedded surgical specimens.

  Through study completion an average of one year

• To determine feasibility of cooperative interaction between multiple sites

  End of study enrollment period (approximately 6 years)

Study Arms (1)

Acetazolamide with Temozolomide

EXPERIMENTAL

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.

Drug: Acetazolamide; Drug: Temozolomide

Interventions

Acetazolamide DRUG

ACZ will be given at an initial dose of 250 mg twice a day (BID) and then escalated to 500 mg BID after 1 week. ACZ will be given on days 1-21 of each cycle.

Also known as: Diamox, Diamox Sequels

Acetazolamide with Temozolomide

Temozolomide DRUG

For cycle 1 of the maintenance phase, TMZ will administered at 150 mg/m2 on days 1- 5 followed by 23 days with no drug. For cycles 2- 6, TMZ can be increased to 200 mg/m2 at the discretion of the treating investigator.

Also known as: Temodar

Acetazolamide with Temozolomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven, newly diagnosed IDH wildtype glioblastoma (GBM) that has a methylated MGMT promoter as assessed by the standardized institutional analysis.
• Patients are eligible if they had a prior low grade astrocytoma and there is subsequent histological evidence of a diagnosis of grade III or IV tumor.
• Patients must be receiving TMZ as part of their standard adjuvant treatment regimen following treatment with TMZ and Radiation.
• Patients must have a Karnofsky performance ≥ 60%.
• Normal organ function as follows:
• Absolute Neutrophil Count (ANC) ≥ 1.0 x 10\^9/ L
• Platelets ≥ 100 x 10\^9 / L
• Hemoglobin ≥ 8.0 g / dL
• Age 18 years or older.
• Kidney function (creatinine level within normal institutional limit, or creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine level above institutional normal).
• Liver function (AST/ALT \<2.5 X institutional upper limit of normal (ULN), Total bilirubin ≤ 1.5 times ULN, INR within 1.5 times ULN (or if receiving anticoagulant therapy an INR of ≤ 3.0 is allowed with concomitant increase in PT or an aPTT ≤ 2.5 × control).
• Women able to become pregnant must have a negative pregnancy test within 30 days of registration.
• Patients must have the ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Prior invasive malignancy that is not low-grade glioma (except non-melanomatous skin cancer or carcinoma in situ of the cervix) unless the patient has been disease free and off therapy for that disease for a minimum of 3 years.
• Active systemic infection requiring treatment, including any HIV infection or toxoplasmosis.
• Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration.
• Systemic corticosteroid therapy, \>8 mg of dexamethasone daily (or equivalent) at study enrollment.
• Pregnant women are excluded from this study, where pregnancy is confirmed by a positive serum beta-hCG laboratory test. Breast-feeding should be discontinued.
• Hypersensitivity to acetazolamide or sulfonamides.

Sponsors & Collaborators

• University of Chicago: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Interventions

Acetazolamide; Temozolomide

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dacarbazine; Triazenes; Imidazoles

Study Officials

• Bakhtiar Yamini, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2017
• First Posted: January 5, 2017
• Study Start: October 3, 2018
• Primary Completion: June 26, 2025
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

US (1)