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

NCT03796273 | Terminated Early Phase 1 FDA Drug

• 4 other identifiers: IRB00054587NCI-2018-03087CCCWFU 91118P30CA012197
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 30 days after surgery

Secondary Outcomes (3)

• tGLI1 pathway activation

  Up to 30 days after surgery

• Incidence of adverse events (AEs)

  Up to 30 days after surgery

• Blood brain penetrance of ketoconazole in serum relative to enhancing brain tissue

  Up to 30 days after surgery

Other Outcomes (4)

• Serum ketoconazole concentrations in Cerebrospinal Fluid (CSF)

  Up to 30 days after surgery

• Serum ketoconazole concentrations in enhancing brain tissue

  Up to 30 days after surgery

• Serum ketoconzcole concentrations in unenhancing brain tissue

  Up to 30 days after surgery

Study Arms (2)

Arm I (ketoconazole)

EXPERIMENTAL

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

Arm II (standard surgery)

ACTIVE COMPARATOR

Patients undergo standard surgery.

Other: Best Practice

Interventions

Best Practice OTHER

Undergo standard surgery

Also known as: standard of care, standard therapy

Arm I (ketoconazole); Arm II (standard surgery)

Ketoconazole DRUG

Given PO

Also known as: Fungarest, Fungoral, Ketoderm, Ketoisdin, Nizoral, Orifungal M, Panfungol, R-41400, Xolegel

Arm I (ketoconazole)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 18 years old
• Subjects must have a history of:
• Histologically confirmed primary breast cancer including primary invasive and metastatic breast cancers with imaging findings consistent with brain metastasis. In the event that a patient presents with an initial diagnosis of metastatic breast cancer with imaging findings of a new brain metastases and unequivocal imaging findings of a primary breast cancer, consideration for study enrollment requires approval from the study chair (primary cohort)
• 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.
• Subjects must be undergoing surgical resection for clinical purposes with anticipated resection of at least 300 mg of tissue.
• Patients with any prior number of radiation (including brain radiation), chemotherapy, or surgical interventions will be eligible for this protocol.
• The effects of ketoconazole on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document (either directly or via a legally authorized representative).

You may not qualify if:

• Subjects with contraindication to ketoconazole including:
• Prior allergic reaction or intolerance of ketoconazole
• Known active hepatitis
• QTc prolongation (based on electrocardiography \[EKG\] obtained within 21 days of enrollment, with a threshold of \>450 ms in males and \>470 ms in female)
• Known liver cirrhosis will be excluded from enrollment
• Positive serum pregnancy test within 21 days of enrollment
• Subjects currently taking medications that are included in the contraindicated concurrent medications section of the Food and Drug Administration (FDA) approved indications for ketoconazole will be required to complete a seven day wash out period prior to consideration for enrollment.
• Subjects for whom collection of blood, or tissue samples is unsafe or clinically inadvisable.
• Pregnant women are excluded from this study because ketoconazole is a Class B agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ketoconazole, breastfeeding should be discontinued if the mother is treated with ketoconazole.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Astrocytoma; Glioma; Oligodendroglioma

Interventions

Practice Guidelines as Topic; Standard of Care; Ketoconazole

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Guidelines as Topic; Quality Assurance, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality Indicators, Health Care; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Roy Strowd, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2018
• First Posted: January 8, 2019
• Study Start: March 13, 2019
• Primary Completion: October 23, 2022
• Study Completion: October 23, 2022
• Last Updated: March 20, 2026

Record last verified: 2026-03

Locations

US (1)