Study of Letrozole in Recurrent Gliomas
- Conditions
- Brain Tumor
- Interventions
- Registration Number
- NCT03122197
- Lead Sponsor
- University of Cincinnati
- Brief Summary
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 39
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Letrozole Letrozole Oral Tablet 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 â„ 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 Letrozole Oral Tablet 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. Previously Received letrozole and temozolomide Letrozole Oral Tablet 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. Letrozole and temozolomide Temozolomide 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. Previously Received letrozole and temozolomide Temozolomide 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.
- Primary Outcome Measures
Name Time Method Overall Letrozole AUC in tumor tissue. 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 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.
- Secondary Outcome Measures
Name Time Method Adverse Events The time patients remain on treatment until 30 days after treatment completed The number of patients with treatment related toxicity will be assessed using CTCAE v4.0
Progression free Survival From start of treatment until time of progression assessed up to 1 year Patients will be followed for response using RANO criteria to determine time from start of treatment to progression.
Overall Survival From start of treatment until time of death assessed up to 1 year Patients will be followed from start of treatment until time of death
Trial Locations
- Locations (1)
University of Cincinnati
đșđžCincinnati, Ohio, United States