An Early Phase 1 interventional study of Best Practice and Ketoconazole in Anatomic Stage IV Breast Cancer AJCC v8, Astrocytoma and Breast Carcinoma Metastatic in the Brain, sponsored by Wake Forest University Health Sciences. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-31.
Sponsored by Wake Forest University Health Sciences · Early Phase 1, Interventional, and Treatment
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.
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.
420 studies on the registry are indexed under Astrocytoma; 76 are open to participants now.
This study's enrollment of 15 is below the median of 30 across 346 interventional studies indexed under Astrocytoma.
Browse Astrocytoma studies →Wake Forest University Health Sciences is the lead sponsor of 1,320 studies on the registry; 199 are open to participants now.
Of its 323 completed or terminated interventional studies of FDA-regulated products, 243 (75%) have results posted.
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Subjects must have a history of:
OR
Histologically confirmed primary glioma including astrocytoma or oligodendroglioma of any World Health Organization grade with imaging findings consistent with recurrent or progressive disease (exploratory cohort). Patients with ependymoma will not be included.
Exclusion Criteria:
Subjects with contraindication to ketoconazole including:
Patients receive ketoconazole PO QD on days 1-4 before standard surgery in the absence of disease progression or unacceptable toxicity.
Other: Best Practice · Drug: Ketoconazole
Patients undergo standard surgery.
Other: Best Practice
Undergo standard surgery
Also known as: standard of care, standard therapy
Given PO
Also known as: Fungarest, Fungoral, Ketoderm, Ketoisdin, Nizoral, Orifungal M, Panfungol, R-41400, Xolegel
tGLI1 activation signature 8 (t-GAS 8)
The primary outcome of this study is modulation of the tGLI1 pathway as assessed by the tGLI1 activation signature 8 (t-GAS 8) \[29, 40\]. t-GAS 8 consists of eight validated tGLI1 regulated genes (CD24, CD44, VEGF-A, VEGF-C, VEGFR2, TEM7, OCT-4. and heparanase) and is measured using qPCR in patients whose brain tissue expresses tGLI1 (by IHC). The distribution of the tGAS will be examined and transformed to approximate the conditional normality assumption if necessary. Analysis of variance (ANOVA) methods will be used to determine the effects of different factors of interest (e.g., treatment or tumor type) on the outcomes measured.
Time frame: Up to 30 days after surgery
tGLI1 pathway activation
tGLI1 pathway activation will be compared between treatment groups using ANOVA as described for the analysis of primary objective.
Time frame: Up to 30 days after surgery
Incidence of adverse events (AEs)
The safety of ketoconazole will be defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0 criteria and determined by adverse event proportions. The adverse event proportions will be compared between treatment groups using chi-squared tests. If feasible, a logistic regression model will be used to detect whether the adverse event proportion is higher in the treatment group after adjusting for the tumor type.
Time frame: Up to 30 days after surgery
Blood brain penetrance of ketoconazole in serum relative to enhancing brain tissue
The analysis will be the same as that for the analysis of primary objective.
Time frame: Up to 30 days after surgery
Serum ketoconazole concentrations in Cerebrospinal Fluid (CSF)
Measured using mass spectroscopy. The analysis will be the same as that for the analysis of primary objective. If the sample size is too small, the nonparametric approach will be considered as the primary analysis.
Time frame: Up to 30 days after surgery
Serum ketoconazole concentrations in enhancing brain tissue
Measured using mass spectroscopy. The analysis will be the same as that for the analysis of primary objective. If the sample size is too small, the nonparametric approach will be considered as the primary analysis.
Time frame: Up to 30 days after surgery
Serum ketoconzcole concentrations in unenhancing brain tissue
Measured using mass spectroscopy. The analysis will be the same as that for the analysis of primary objective. If the sample size is too small, the nonparametric approach will be considered as the primary analysis.
Time frame: Up to 30 days after surgery
Changes in tGLI1 signaling pathway
Will be calculated and compared between treatment groups. Ideally analysis of covariance should be done. However, due to the small sample size, ANOVA as described for the primary analysis approach or the 2-sample t test will be used. If needed, non-parametric approaches will be used instead.
Time frame: Baseline up to 30 days after surgery
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Wake Forest University Health Sciences