Brain TumorEarly Phase 1NCT03122197
Study of Letrozole in Recurrent Gliomas
A Early Phase 1 study testing Letrozole Oral Tablet and Temozolomide in people with Brain Tumor, run by University of Cincinnati at 1 site in United States.
Trial summary
The purpose of this study is to determine the ability of letrozole to penetrate the blood brain barrier and concentrate in gliomas. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Tumor
- What is being tested?
- Letrozole Oral Tablet and Temozolomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- 16 May 2017to Dec 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
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
- Radiographically, histologically or cytologically confirmed recurrent brain high grade glioma with plan for resection or biopsy.
- Inclusion #1 for Sub-study Only: Radiographically, histologically or cytologically confirmed recurrent brain high grade glioma.
- Age >18 years.
- ECOG performance status 0 -2 (Karnofsky >60%, see Appendix A).
- CBC/differential obtained within 28 days prior to registration on study, with adequate bone marrow function defined as follows:
- Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3;
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- Platelets ≥ 100,000 cells/mm3;
- Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable).
- Adequate hepatic function, defined as follows:
- Total bilirubin < 2 x institutional ULN within 14 days prior to registration;
- AST or ALT < 3 x institutional ULN within 14 days prior to registration.
- Adequate renal function, defined as GFR > 30 ml/min or Cr < 1.5.
- Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential.
- Imaging prior to treatment including MRI of brain (with contrast preferred but not required).
- Ability to understand and the willingness to sign a written informed consent document.
- Inclusion #10 for Sub-study Only: Measurable disease per RANO criteria within 28 days of starting treatment on this study.
Who cannot join
- Patients may not be receiving any other investigational agents.
- History of allergic reactions attributed to letrozole or other agents used in study.
- Exclusion #2 for Sub-study Only: History of allergic reactions attributed to letrozole or TMZ.
- Uncontrolled intercurrent illness including, but not limited to, ongoing significant or serious active cardiovascular disease (CHF exacerbation, unstable angina or MI in last 6 months), or infection including the diagnosis of AIDS or active hepatitis B or C infection, or psychiatric illness or medical or personal conditions that in the opinion of the investigator would limit the patient's ability to participate.
- Patients attempting to conceive, and pregnant or nursing women are excluded from this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Cincinnati
Cincinnati, Ohio, 45267
Lalanthica Yogendran, MD, PhD
About this study
Official title: A Phase 0/1 Pharmacokinetic and Pharmacodynamics and Safety and Tolerability Study of Letrozole in Combination With Standard Therapy in Recurrent High Grade Gliomas
The purpose of this study is to determine the ability of letrozole to penetrate the blood brain barrier and concentrate in gliomas.
Read the detailed description
Nine to forty-two (42 patients only if every cohort required expansion) total patients were planned for the main BN-16-01 phase 0/1 study to explore the ability of letrozole to penetrate the blood brain barrier and gliomas. As of November 2023 The BN-16-01 main study has completed active recruitment (20 subjects were accrued) and all safety and pharmacokinetics data have been analyzed with subsequent publications pending. Characterization of the safety and pharmacokinetics of letrozole in combination with standard of care treatments, such as TMZ has been completed for the main study and provides the rationale for initiation of a sub-study.
A new sub-study "Letrozole and Temozolomide" expansion cohort has been opened to accrual. This Phase 1 expansion cohort of letrozole 15mg administered in combination with 50 mg/m2 metronomic temozolomide (TMZ) in patients with high grade gliomas. 19 subjects total (2 historical subjects from the main study and 17 new accruals) will be enrolled into this expansion cohort.
- Conditions
- Brain Tumor
- Being tested
- Letrozole Oral Tablet, Temozolomide
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Letrozole Oral TabletDrug
Also called Femara
Administration: Letrozole will be given orally once daily.
TemozolomideDrug
Also called Temodar
50 mg/m2 TMZ administered orally once daily
| Study group | Role | What they receive |
|---|---|---|
| Letrozole | Experimental | The BN-16-01 main study treatment starting dose will be 2.5mg administered orally once daily. Daily doses up to 10mg and single doses of 30mg have been shown to be safe in prior studies and therefore we expect that letrozole doses up to 20mg in this study will be safe.
The recommended phase II dose (RP2D) will be considered the dose that results in ≥ 2uM letrozole concentration in the tumor or the highest dose achieved (20mg daily for cohort level 7) with < 2/6 patients with DLTs. This dose will be planned for future phase II studies to determine potential efficacy. Receives: Drug: Letrozole Oral Tablet |
| Letrozole and temozolomide | Experimental | Phase 1 expansion cohort of letrozole 15mg administered in combination with 50 mg/m2 metronomic temozolomide (TMZ) in patients with high grade gliomas. Letrozole 15mg will be administered orally once daily for a 7-day lead-in period. After 7 days subjects will continue letrozole in combination 50 mg/m2 TMZ administered orally once daily. Receives: Drug: Letrozole Oral Tablet; Drug: Temozolomide |
| Previously Received letrozole and temozolomide | Experimental | Phase 1 expansion cohort of two identified subjects with gliomas who previously participated in the main study UCCI-BN-16-01 who received as physician's choice of treatment 50 mg/m2 TMZ in combination with dosing of 15 mg letrozole. Receives: Drug: Letrozole Oral Tablet; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Letrozole AUC in tumor tissue.
Pharmacokinetic modeling will be used to determine the overall AUC in the tumor tissue to assess for letrozole penetration through blood brain barrier.
Measured: 5 days
Progression free survival in letrozole and temozolomide combination
Sub-study expansion cohort only: Progression free survival using RANO criteria at 6 months from the start of the combination of 15 mg letrozole and 50 mg/m2 temozolomide.
Measured: 6 months
Secondary outcomes (3)
Adverse Events
The number of patients with treatment related toxicity will be assessed using CTCAE v4.0
Measured: The time patients remain on treatment until 30 days after treatment completed
Progression free Survival
Patients will be followed for response using RANO criteria to determine time from start of treatment to progression.
Measured: From start of treatment until time of progression assessed up to 1 year
Overall Survival
Patients will be followed from start of treatment until time of death
Measured: From start of treatment until time of death assessed up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2017
- Study start16 May 2017
- Primary completion1 Sep 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain TumorStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lalanthica Yogendran, University of Cincinnati
- Investigators
- Lalanthica Yogendran, MD, Principal investigator, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03122197
- Sponsor's protocol ID
- UCCI-BN-16-01
- Status last verified
- Apr 2026
- First submitted
- 10 Apr 2017
- Last updated
- 18 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 0/1 Pharmacokinetic and Pharmacodynamics and Safety and Tolerability Study of Letrozole in Combination With Standard Therapy in Recurrent High Grade Gliomas
- ClinicalTrials.gov ID
- NCT03122197
- Acronym / sponsor ID
- UCCI-BN-16-01
- Conditions
- Brain Tumor
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 39 participants (estimated)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Study start
- 16 May 2017 (actual)
- Primary completion
- 1 Sep 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 20 Apr 2017 (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.
The purpose of this study is to determine the ability of letrozole to penetrate the blood brain barrier and concentrate in gliomas.
Detailed description
Nine to forty-two (42 patients only if every cohort required expansion) total patients were planned for the main BN-16-01 phase 0/1 study to explore the ability of letrozole to penetrate the blood brain barrier and gliomas. As of November 2023 The BN-16-01 main study has completed active recruitment (20 subjects were accrued) and all safety and pharmacokinetics data have been analyzed with subsequent publications pending. Characterization of the safety and pharmacokinetics of letrozole in combination with standard of care treatments, such as TMZ has been completed for the main study and provides the rationale for initiation of a sub-study.
A new sub-study "Letrozole and Temozolomide" expansion cohort has been opened to accrual. This Phase 1 expansion cohort of letrozole 15mg administered in combination with 50 mg/m2 metronomic temozolomide (TMZ) in patients with high grade gliomas. 19 subjects total (2 historical subjects from the main study and 17 new accruals) will be enrolled into this expansion cohort.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Letrozole | Experimental | Drug: Letrozole Oral TabletThe BN-16-01 main study treatment starting dose will be 2.5mg administered orally once daily. Daily doses up to 10mg and single doses of 30mg have been shown to be safe in prior studies and therefore we expect that letrozole doses up to 20mg in this study will be safe. The recommended phase II dose (RP2D) will be considered the dose that results in ≥ 2uM letrozole concentration in the tumor or the highest dose achieved (20mg daily for cohort level 7) with < 2/6 patients with DLTs. This dose will be planned for future phase II studies to determine potential efficacy. |
| Letrozole and temozolomide | Experimental | Drug: Letrozole Oral Tablet, Drug: TemozolomidePhase 1 expansion cohort of letrozole 15mg administered in combination with 50 mg/m2 metronomic temozolomide (TMZ) in patients with high grade gliomas. Letrozole 15mg will be administered orally once daily for a 7-day lead-in period. After 7 days subjects will continue letrozole in combination 50 mg/m2 TMZ administered orally once daily. |
| Previously Received letrozole and temozolomide | Experimental | Drug: Letrozole Oral Tablet, Drug: TemozolomidePhase 1 expansion cohort of two identified subjects with gliomas who previously participated in the main study UCCI-BN-16-01 who received as physician's choice of treatment 50 mg/m2 TMZ in combination with dosing of 15 mg letrozole. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Radiographically, histologically or cytologically confirmed recurrent brain high grade glioma with plan for resection or biopsy.
- Age >18 years.
- ECOG performance status 0 -2 (Karnofsky >60%, see Appendix A).
- CBC/differential obtained within 28 days prior to registration on study, with adequate bone marrow function defined as follows:
- Adequate hepatic function, defined as follows:
Key exclusion criteria (5 listed)
- Patients may not be receiving any other investigational agents.
- History of allergic reactions attributed to letrozole or other agents used in study.
- Exclusion #2 for Sub-study Only: History of allergic reactions attributed to letrozole or TMZ.
- Uncontrolled intercurrent illness including, but not limited to, ongoing significant or serious active cardiovascular disease (CHF exacerbation, unstable angina or MI in last 6 months), or infection including the diagnosis of AIDS or active hepatitis B or C infection, or psychiatric illness or medical or personal conditions that in the opinion of the investigator would limit the patient's ability to participate.
- Patients attempting to conceive, and pregnant or nursing women are excluded from this study.
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 |
|---|---|---|
| Letrozole Oral TabletAlso: FemaraAdministration: Letrozole will be given orally once daily. | Drug | Letrozole, Letrozole and temozolomide, Previously Received letrozole and temozolomide |
| TemozolomideAlso: Temodar50 mg/m2 TMZ administered orally once daily | Drug | Letrozole and temozolomide, Previously Received letrozole and temozolomide |
Primary outcome
Overall Letrozole AUC in tumor tissue.
Time frame: 5 days
Pharmacokinetic modeling will be used to determine the overall AUC in the tumor tissue to assess for letrozole penetration through blood brain barrier.
Progression free survival in letrozole and temozolomide combination
Time frame: 6 months
Sub-study expansion cohort only: Progression free survival using RANO criteria at 6 months from the start of the combination of 15 mg letrozole and 50 mg/m2 temozolomide.
3 secondary outcomes
Adverse Events
Time frame: The time patients remain on treatment until 30 days after treatment completed
Progression free Survival
Time frame: From start of treatment until time of progression assessed up to 1 year
Overall Survival
Time frame: From start of treatment until time of death assessed up to 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2026.
- Individual participant dataSharing planned: No
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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.
Lalanthica Yogendran, MD principal investigator
University of Cincinnati
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 Letrozole Oral Tablet and Temozolomide in people with Brain Tumor, run by University of Cincinnati 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 16 inclusion and 5 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: looking for participants now, as of the sponsor's last update on 18 Aug 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact UC Cancer Center Clinical Trials Office (513-584-7698, cancer@uchealth.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Letrozole AUC in tumor tissue. (time frame: 5 days). The study lists 2 primary outcomes in all. 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 18 Aug 2026.