Acetazolamide Sodium and Temozolomide in Treating Adult Patients with Newly Diagnosed MGMT Promoter-Methylated Malignant Glioma

Status: Active

Description

This phase I trial studies the side effects and best dose of acetazolamide sodium when given together with temozolomide in treating adult patients with newly diagnosed MGMT promoter-methylated malignant glioma. Acetazolamide sodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving acetazolamide sodium and temozolomide may work better in treating adult patients with newly diagnosed malignant glioma.

Eligibility Criteria

Inclusion Criteria

  • Histologically proven, newly diagnosed World Health Organization (WHO) grade III or IV astrocytoma that has a methylated MGMT promoter as assessed by the standardized institutional analysis
  • Patients are eligible if they had a prior low grade astrocytoma that was not previously treated, and there is subsequent histological evidence of a diagnosis of grade III or IV astrocytoma
  • Patients are eligible if they are going to receive TMZ as part of the standard adjuvant treatment regimen following concomitant TMZ/radiation therapy (RT)
  • Patients must have a Karnofsky performance >= 60%
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/ L
  • Platelets >= 100 x 10^9 / L
  • Hemoglobin >= 8.0 g / dL
  • Creatinine level within normal institutional limit, or creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine level above institutional normal
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 X institutional upper limit of normal
  • Total bilirubin =< 1.5 times upper limit of normal (ULN)
  • International normalized ratio (INR) within 1.5 times ULN (or if receiving anticoagulant therapy an INR of =< 3.0 is allowed with concomitant increase in prothrombin time (PT) or an activated partial thromboplastin time (aPTT) =< 2.5 x control)
  • Women of childbearing potential 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 human immunodeficiency virus (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 (e.g. acidosis, adrenocortical insufficiency, cirrhosis)
  • 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-human chorionic gonadotropin (hCG) laboratory test; breast-feeding should be discontinued
  • Hypersensitivity to acetazolamide or sulfonamides

Locations & Contacts

Illinois

Chicago
Northwestern University
Status: Active
Contact: Rimas Vincas Lukas
Phone: 312-695-1301
Email: rimas.lukas@nm.org
University of Chicago Comprehensive Cancer Center
Status: Active
Contact: Bakhtiar Yamini
Phone: 773-834-3288
Email: byamini@surgery.bsd.uchicago.edu
University of Illinois
Status: Active
Contact: Tony Cornelious
Phone: 312-996-9749
Email: tcornel@uic.edu
Decatur
Decatur Memorial Hospital
Status: Active
Contact: James Lloyd Wade
Phone: 217-876-6600
Email: jlwade3@sbcglobal.net
Evanston
NorthShore University HealthSystem-Evanston Hospital
Status: Active
Contact: Ryan Thomas Merrell
Phone: 847-570-2570
Email: rmerrell@northshore.org
Peoria
Illinois CancerCare-Peoria
Status: Active
Contact: Francois J. Geoffroy
Phone: 309-243-3000
Email: fgeoffroy@illinoiscancercare.com
Warrenville
Northwestern Medicine Cancer Center Warrenville
Status: Active
Contact: Vinai Gondi
Phone: 630-532-5450
Email: vinai.gondi@nm.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

I. To describe the objective response rate (ORR), progression free survival (PFS) and overall survival (OS).

II. To determine the feasibility of the cooperative interaction between BrainUp, the University of Chicago Medical Center, NorthShore University HealthSystem, Northwestern Memorial Hospital, Central Dupage Hospital and University of Illinois Chicago Medical Center.

III. To evaluate Bcl-3 expression level within each tumor and to preliminarily examine the ability of Bcl-3 to predict response to temozolomide (TMZ) and the efficacy of adding acetazolamide sodium (ACZ).

OUTLINE: This is a dose-escalation study of acetazolamide sodium.

CONCOMITANT PHASE: Patients receive temozolomide orally (PO) daily on days 1-42 while undergoing focal radiotherapy.

MAINTENANCE PHASE: Patients receive temozolomide PO daily on days 1-5 and acetazolamide sodium PO twice daily (BID) on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
University of Chicago Comprehensive Cancer Center

Principal Investigator
Bakhtiar Yamini

Trial IDs

Primary ID IRB16-0767
Secondary IDs NCI-2017-00753
Clinicaltrials.gov ID NCT03011671