Clinical trial NCT03122197: Study of Letrozole in Recurrent Gliomas
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Brain Tumor
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
First posted: 2017-04-20
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Overall Letrozole AUC in tumor tissue.
timeFrame: 5 days
measure: Progression free survival in letrozole and temozolomide combination
timeFrame: 6 months
Secondary outcomes:
measure: Adverse Events
timeFrame: The time patients remain on treatment until 30 days after treatment completed
measure: Progression free Survival
timeFrame: From start of treatment until time of progression assessed up to 1 year
measure: Overall Survival
timeFrame: From start of treatment until time of death assessed up to 1 year
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: Trisha Wise-Draper, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: