Letrozole treatment for recurrent brain tumors

A Phase 0/1 Pharmacokinetic and Pharmacodynamics and Safety and Tolerability Study of Letrozole in Combination With Standard Therapy in Recurrent High Grade Gliomas

This study is testing if letrozole, when used with another drug, can safely help people with recurrent high-grade brain tumors.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 39 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Cincinnati (Academic / other)
• Locations: 1 site (Cincinnati, Ohio)
• Trial ID: NCT03122197 on ClinicalTrials.gov

What this trial studies

This study investigates the ability of letrozole to penetrate the blood-brain barrier and concentrate in gliomas, specifically in patients with recurrent high-grade gliomas. It includes a sub-study where letrozole is administered alongside metronomic temozolomide to assess safety and pharmacokinetics. A total of 19 patients will be enrolled in this expansion cohort, building on previous findings from the main study. The goal is to evaluate the effectiveness of this combination therapy in treating recurrent brain tumors.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with confirmed recurrent high-grade gliomas and a plan for resection or biopsy.

Not a fit: Patients with low-grade gliomas or those not meeting the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with recurrent high-grade gliomas.

How similar studies have performed: While this approach is novel in the context of gliomas, previous studies have shown promise in using letrozole for other conditions, indicating potential for success.

Eligibility criteria

Inclusion Criteria

1. 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.
2. Age \>18 years.
3. ECOG performance status 0 -2 (Karnofsky \>60%, see Appendix A).
4. 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).
5. 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.
6. Adequate renal function, defined as GFR \> 30 ml/min or Cr \< 1.5.
7. Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential.
8. Imaging prior to treatment including MRI of brain (with contrast preferred but not required).
9. Ability to understand and the willingness to sign a written informed consent document.
10. Inclusion #10 for Sub-study Only: Measurable disease per RANO criteria within 28 days of starting treatment on this study.

Exclusion Criteria

1. Patients may not be receiving any other investigational agents.
2. 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.
3. 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.
4. Patients attempting to conceive, and pregnant or nursing women are excluded from this study.

Where this trial is running

Cincinnati, Ohio

• University of Cincinnati — Cincinnati, Ohio, United States (Recruiting)

Study contacts

• Principal investigator: Trisha Wise-Draper, MD, PhD — University of Cincinnati
• Study coordinator: UC Cancer Center Clinical Trials Office

Conditions Brain Tumor