Study of Letrozole in Recurrent Gliomas

Conditions

Letrozole Oral Tablet — DRUG
Administration: Letrozole will be given orally once daily.
Temozolomide — DRUG
50 mg/m2 TMZ administered orally once daily

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

Experimental: Letrozole
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.
Experimental: Letrozole and 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.
Experimental: Previously Received letrozole and 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.

Overall Letrozole AUC in tumor tissue. [ Time Frame: 5 days ]

Facility	City	State	ZIP	Site coordinators
University of Cincinnati	Cincinnati	Ohio	45267	Trisha Wise-Draper, MD, PhD

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