Phase I Study of Safety and Tolerability of Acetazolamide With Temozolomide
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|ClinicalTrials.gov Identifier: NCT03011671|
Recruitment Status : Not yet recruiting
First Posted : January 5, 2017
Last Update Posted : April 25, 2018
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 temazolomide (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.
|Condition or disease||Intervention/treatment||Phase|
|Malignant Glioma of Brain||Drug: Acetazolamide Drug: Temozolomide||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Safety and Tolerability of Acetazolamide With Temozolomide in Adults With Newly Diagnosed MGMT Promoter-Methylated Malignant Glioma|
|Estimated Study Start Date :||December 2018|
|Estimated Primary Completion Date :||February 2020|
|Estimated Study Completion Date :||March 2020|
Experimental: Acetazolamide with Temozolomide
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.
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.
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.
Other Name: Temodar
- Number of participants with adverse events [ Time Frame: 28 Days ]To determine the safety, tolerability and adverse event profile of adding acetazolamide to temozolomide in patients with newly diagnosed malignant glioma.
- Measure objective response rate (ORR); change in tumor size [ Time Frame: 6 months ]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 Frame: 6 months ]
- 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 ]
- Analysis of formalin fixed paraffin embedded surgical specimens. [ Time Frame: Through study completion an average of one year ]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 learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03011671
|Contact: Bakhtiar Yamini, M.D.||firstname.lastname@example.org|
|United States, Illinois|
|University of Chicago Medical Center||Not yet recruiting|
|Chicago, Illinois, United States, 60637|
|Contact: Bakhtiar Yamini, MD email@example.com|
|Principal Investigator:||Bakhtiar Yamini, MD||University of Chicago|