Anatomic Stage IV Breast Cancer AJCC v8Early Phase 1NCT03796273
Ketoconazole Before Surgery in Treating Patients With Recurrent Glioma or Breast Cancer Brain Metastases
A Early Phase 1 study testing Best Practice and Ketoconazole in people with Anatomic Stage IV Breast Cancer AJCC v8 and Astrocytoma, run by Wake Forest University Health Sciences at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anatomic Stage IV Breast Cancer AJCC v8, Astrocytoma, Breast Carcinoma Metastatic in the Brain
- What is being tested?
- Best Practice and Ketoconazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Mar 2019to 23 Oct 2022
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
- 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.
- Subjects must be undergoing surgical resection for clinical purposes with anticipated resection of at least 300 mg of tissue.
Show all 9Show fewer
- 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).
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
Official title: tGLI1 as a Therapeutic Target in Brain Metastases: A Window of Opportunity Study in Breast Cancer Brain Metastases and Primary Gliomas
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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
- Being tested
- Best Practice, Ketoconazole
- Medical subject headings
- Astrocytoma, Glioma, Oligodendroglioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Best PracticeOther
Also called standard of care, standard therapy
Undergo standard surgery
KetoconazoleDrug
Also called Fungarest, Fungoral, Ketoderm, Ketoisdin
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Best Practice; Drug: Ketoconazole |
| Arm II (standard surgery) | Active comparator | Patients undergo standard surgery. Receives: Other: Best Practice |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 30 days after surgery
Secondary outcomes (3)
tGLI1 pathway activation
tGLI1 pathway activation will be compared between treatment groups using ANOVA as described for the analysis of primary objective.
Measured: 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.
Measured: 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.
Measured: Up to 30 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2019
- Study start13 Mar 2019
- Primary completion23 Oct 2022
- Study completion23 Oct 2022
Why it stopped: Low accruals
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anatomic Stage IV Breast Cancer AJCC v8Studies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Roy Strowd, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03796273
- Sponsor's protocol ID
- IRB00054587
- Other IDs
- NCI-2018-03087, CCCWFU 91118, P30CA012197
- Status last verified
- Jul 2026
- First submitted
- 26 Dec 2018
- Last updated
- 31 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- tGLI1 as a Therapeutic Target in Brain Metastases: A Window of Opportunity Study in Breast Cancer Brain Metastases and Primary Gliomas
- ClinicalTrials.gov ID
- NCT03796273
- Acronym / sponsor ID
- IRB00054587
- Conditions
- Anatomic Stage IV Breast Cancer AJCC v8, Astrocytoma, Breast Carcinoma Metastatic in the Brain, Glioma, Invasive Breast Carcinoma, Oligodendroglioma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accruals
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 13 Mar 2019 (actual)
- Primary completion
- 23 Oct 2022 (actual)
- Study completion
- 23 Oct 2022 (actual)
- First posted
- 8 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (ketoconazole) | Experimental | Other: Best Practice, Drug: KetoconazolePatients receive ketoconazole PO QD on days 1-4 before standard surgery in the absence of disease progression or unacceptable toxicity. |
| Arm II (standard surgery) | Active comparator | Other: Best PracticePatients undergo standard surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age greater than or equal to 18 years old
- 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)
- 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.
Key exclusion criteria (9 listed)
- Subjects with contraindication to ketoconazole including:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Best PracticeAlso: standard of care, standard therapyUndergo standard surgery | Other | Arm I (ketoconazole), Arm II (standard surgery) |
| KetoconazoleAlso: Fungarest, Fungoral, Ketoderm, KetoisdinGiven PO | Drug | Arm I (ketoconazole) |
Primary outcome
tGLI1 activation signature 8 (t-GAS 8)
Time frame: Up to 30 days after surgery
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.
3 secondary outcomes
tGLI1 pathway activation
Time frame: Up to 30 days after surgery
Incidence of adverse events (AEs)
Time frame: Up to 30 days after surgery
Blood brain penetrance of ketoconazole in serum relative to enhancing brain tissue
Time frame: Up to 30 days after surgery
Results and safety
The study was stopped early (reason given: Low accruals). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2026.
Related trials for Anatomic Stage IV Breast Cancer AJCC v8
RecruitingPhase 2
Testing the Addition of an Individualized Vaccine to Durvalumab and Tremelimumab and Chemotherapy in Patients With Metastatic Triple Negative Breast Cancer
Anatomic Stage IV Breast Cancer AJCC v8, Invasive Breast Carcinoma
Active, not recruitingPhase 2
Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations
Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8
RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
Active, not recruiting
Positron Emission Tomography in Women With Advanced HER2-Positive Breast Cancer
Breast Cancer, Stage IV Breast Cancer
Active, not recruitingPhase 2
Nab-Paclitaxel in Treating Older Patients With Locally Advanced or Metastatic Breast Cancer
Locally Advanced Breast Carcinoma, Metastatic Breast Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roy Strowd, MD principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Best Practice and Ketoconazole in people with Anatomic Stage IV Breast Cancer AJCC v8 and Astrocytoma, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low accruals). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
tGLI1 activation signature 8 (t-GAS 8) (time frame: Up to 30 days after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.