Study of Letrozole in Recurrent Gliomas

NCT03122197 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: UCCI-BN-16-01
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the ability of letrozole to penetrate the blood brain barrier and concentrate in gliomas.

Conditions

Brain Tumor

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  6 months

Secondary Outcomes (3)

• Adverse Events

  The time patients remain on treatment until 30 days after treatment completed

• Progression free Survival

  From start of treatment until time of progression assessed up to 1 year

• Overall Survival

  From start of treatment until time of death assessed up to 1 year

Study Arms (3)

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.

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.

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.

Drug: Letrozole Oral Tablet; Drug: Temozolomide

Interventions

Letrozole Oral Tablet DRUG

Administration: Letrozole will be given orally once daily.

Also known as: Femara

Letrozole; Letrozole and temozolomide; Previously Received letrozole and temozolomide

Temozolomide DRUG

50 mg/m2 TMZ administered orally once daily

Also known as: Temodar

Letrozole and temozolomide; Previously Received letrozole and temozolomide

Eligibility Criteria

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

You may qualify if:

• 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:
• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3;
• 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.

You may not qualify if:

• Patients may not be receiving any other investigational agents.
• History of allergic reactions attributed to letrozole or other agents used in study.
• 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.

Sponsors & Collaborators

• University of Cincinnati: lead

Study Sites (1)

University of Cincinnati

Cincinnati, Ohio, 45267, United States

RECRUITING

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Letrozole; Temozolomide

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dacarbazine; Triazenes; Imidazoles

Study Officials

• Trisha Wise-Draper, MD, PhD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Central Study Contacts

UC Cancer Center Clinical Trials Office

CONTACT

513-584-7698; cancer@uchealth.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 10, 2017
• First Posted: April 20, 2017
• Study Start: May 16, 2017
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)