NCT03796273

Ketoconazole Before Surgery in Treating Patients With Recurrent Glioma or Breast Cancer Brain Metastases

tGLI1 as a Therapeutic Target in Brain Metastases: A Window of Opportunity Study in Breast Cancer Brain Metastases and Primary Gliomas

• Status: Terminated
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: Wake Forest University Health Sciences · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This trial studies the side effects and how well ketoconazole works before surgery in treating patients with glioma that has come back or breast cancer that has spread to the brain. Ketoconazole is an antifungal drug that may be able to block a protein, tGLI1 and may help to treat brain tumors.

Detailed description

PRIMARY OBJECTIVES: I. To determine if ketoconazole alters the tGLI1 activation signature (tGAS) which is consisted of eight validated tGLI1 regulated genes (CD24, CD44, VEGF-A, VEGF-C, VEGFR2, TEM7, OCT-4. and heparanase) in tGLI1 expressing brain biospecimens. SECONDARY OBJECTIVES: I. To determine if pre-treatment with ketoconazole, an inhibitor of the tGLI1 pathway in tissue culture and animal models, reduces circulating tGLI1 associated exosomal miRNA expression (miR1290 and miR1246) in brain tumor patients. II. To describe the safety of ketoconazole when administered peri-operatively to patients with primary and secondary brain tumors. III. To measure the blood brain penetrance of ketoconazole in serum relative to enhancing brain tissue. EXPLORATORY OBJECTIVES: I. To measure blood brain penetration of ketoconazole in serum relative to cerebrospinal fluid (CSF) and serum relative to non-enhancing brain tissue (exploratory recurrent glioma patients only). II. To compare tGLI1 expression and pathway modulation with ketoconazole pre-treatment in patients with recurrent gliomas relative to breast cancer brain metastases (BCBM). III. To determine the overall survival and toxicity outcomes for patients that continue ketoconazole after surgery, at the discretion of the treating physician. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive ketoconazole orally (PO) once daily (QD) on days 1-4 before standard surgery in the absence of disease progression or unacceptable toxicity. ARM II: Patients undergo standard surgery. After completion of study treatment, patients are followed up at 30 days.

Conditions

• Anatomic Stage IV Breast Cancer AJCC v8
• Astrocytoma
• Breast Carcinoma Metastatic in the Brain
• Glioma
• Invasive Breast Carcinoma
• Oligodendroglioma
• Prognostic Stage IV Breast Cancer AJCC v8
• Recurrent Glioma

Interventions

Type	Name	Description
OTHER	Best Practice	Undergo standard surgery
DRUG	Ketoconazole	Given PO

Timeline

• Start date: 2019-03-13
• Primary completion: 2022-10-23
• Completion: 2022-10-23
• First posted: 2019-01-08
• Last updated: 2026-03-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study