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

Primary Purpose

Malignant Glioma of Brain

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Acetazolamide

Temozolomide

About this trial

This is an interventional treatment trial for Malignant Glioma of Brain focused on measuring Malignant Glioma of Brain, Acetazolamide, Temozolomide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Sites / Locations

University of Chicago Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Acetazolamide with Temozolomide

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

ORR will be determined at 6 months and is based on the change in tumor size (as determined by Response Assessment in Neuro-Oncology Criteria (RANO) criteria) at the indicated time relative to the pre-treatment scan. RANO criteria will also be used to define disease status (CR, PR, etc.).

Time until progression free survival (PFS)

Time until overall survival (OS)

Analysis of formalin fixed paraffin embedded surgical specimens.

Bcl-3 expression will be determined by an independent neuro-pathologist by immunohistochemical analysis of formalin fixed paraffin embedded (FFPE) surgical specimens. This is to evaluate Bcl-3 expression level within each tumor and preliminarily examine the ability of Bcl-3 to predict response to TMZ and the efficacy of adding ACZ.

To determine feasibility of cooperative interaction between multiple sites

Feasibility to be determined based on ability to complete accrual to the study

Full Information

NCT ID

NCT03011671

First Posted

January 4, 2017

Last Updated

March 2, 2023

Sponsor

University of Chicago

1. Study Identification

Unique Protocol Identification Number

NCT03011671

Brief Title

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

Official Title

A Phase I Study of Safety and Tolerability of Acetazolamide With Temozolomide in Adults With Newly Diagnosed MGMT Promoter-Methylated IDH Wildtype Glioblastoma

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 3, 2018 (Actual)

Primary Completion Date

October 1, 2026 (Anticipated)

Study Completion Date

October 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Chicago

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Malignant Glioma of Brain

Keywords

Malignant Glioma of Brain, Acetazolamide, Temozolomide

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Acetazolamide with Temozolomide

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Acetazolamide

Other Intervention Name(s)

Diamox, Diamox Sequels

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Temozolomide

Other Intervention Name(s)

Temodar

Intervention Description

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.

Primary Outcome Measure Information:

Title

Number of participants with adverse events

Description

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

Time Frame

28 Days

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

6 months

Title

Time until progression free survival (PFS)

Time Frame

6 months

Title

Time until overall survival (OS)

Time Frame

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

Title

Analysis of formalin fixed paraffin embedded surgical specimens.

Description

Time Frame

Through study completion an average of one year

Title

To determine feasibility of cooperative interaction between multiple sites

Description

Feasibility to be determined based on ability to complete accrual to the study

Time Frame

End of study enrollment period (approximately 6 years)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Bakhtiar Yamini, M.D.

Phone

773-702-2123

byamini@surgery.bsd.uchicago.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bakhtiar Yamini, MD

Organizational Affiliation

University of Chicago

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Chicago Medical Center

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Bakhtiar Yamini, MD

byamini@surgery.bsd.uchicago.edu

12. IPD Sharing Statement

Learn more about this trial

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

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