What side effects are associated with this type of intervention?

Common treatments for brain tumors include chemotherapy, radiation therapy, and targeted therapies. Chemotherapy can lead to peripheral neuropathy, cognitive deficits, and endocrine dysfunctions. Radiation therapy is associated with neurocognitive issues, endocrine problems, and impaired growth in children. Targeted therapies, such as bevacizumab, can cause hypertension, bleeding, and thromboembolic events. Aromatase inhibitors, like Letrozole, primarily used in breast cancer, can result in loss of bone density, fractures, and cardiovascular risks.

What prior FDA approvals exist?

There is limited information on FDA approvals for aromatase inhibitors like Letrozole specifically for brain tumors. However, various other treatments have been approved for brain tumors, including temozolomide for glioblastoma and bevacizumab for recurrent glioblastoma. Investigational therapies such as ONC201 for H3 K27M-mutant gliomas and lutetium Lu 177 vipivotide tetraxetan for PSMA-positive metastatic castration-resistant prostate cancer with brain metastases are also being explored. These treatments highlight the ongoing efforts to find effective therapies for brain tumors.

What other types of research exist?

Promising novel alternatives to Letrozole for brain tumor patients include: 1) Bevacizumab, which has shown efficacy in recurrent glioblastoma; 2) Temozolomide, particularly in dose-intense regimens for recurrent malignant gliomas; 3) Tucatinib combined with Trastuzumab and Capecitabine, which has demonstrated intracranial efficacy in HER2-positive breast cancer with brain metastases; 4) Abemaciclib, which has shown activity in hormone receptor-positive breast cancer with brain metastases; 5) Palbociclib, which has demonstrated intracranial activity in brain metastases with cyclin-dependent kinase pathway alterations.

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Aromatase Inhibitor

Letrozole for Brain Tumor

Phase < 1

Recruiting

Led By Trisha Wise-Draper, MD

Research Sponsored by University of Cincinnati

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age >18 years

ECOG performance status 0 -2 (Karnofsky >60%)

Must not have

History of allergic reactions attributed to letrozole or other agents used in study

Uncontrolled intercurrent illness including ongoing significant or serious active cardiovascular disease, infection including AIDS or active hepatitis B or C infection, psychiatric illness, or medical or personal conditions that would limit participation

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from start of treatment until time of death assessed up to 1 year

Awards & highlights

All Individual Drugs Already Approved

Approved for 10 Other Conditions

No Placebo-Only Group

Summary

This trial is testing if letrozole can reach brain tumors and work with TMZ to treat patients with aggressive brain tumors. Letrozole helps by lowering hormone levels, and TMZ attacks the cancer cells' DNA.

Who is the study for?

This trial is for individuals with recurrent brain gliomas who are scheduled for surgical removal or biopsy. Participants should be relatively active and self-caring (ECOG 0-2) and have satisfactory lab test results. Those currently on other experimental drugs cannot join.

What is being tested?

The study is testing the effectiveness of letrozole, an oral tablet, in reaching and concentrating within brain tumors when combined with temozolomide, a standard chemotherapy drug used to treat brain tumors.

What are the potential side effects?

Potential side effects may include fatigue, nausea, hair loss from temozolomide; and hot flashes, joint pain, and bone thinning from letrozole. Each person's reaction to these medications can vary.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am older than 18 years.

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I can take care of myself but might not be able to do heavy physical work.

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My liver is functioning well according to recent tests.

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My brain tumor is confirmed to be high grade and plans are in place for surgery or biopsy.

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My kidney function is within the normal range.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am allergic to letrozole or similar medications used in this study.

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I do not have any serious ongoing illnesses that would prevent me from participating.

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I am allergic to letrozole or TMZ.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from start of treatment until time of death assessed up to 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from start of treatment until time of death assessed up to 1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and from start of treatment until time of death assessed up to 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall Letrozole AUC in tumor tissue.

Progression free survival in letrozole and temozolomide combination

Secondary study objectives

Adverse Events

Overall Survival

Progression free Survival

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 10 Other Conditions

This treatment demonstrated efficacy for 10 other conditions.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Previously Received letrozole and temozolomideExperimental Treatment2 Interventions

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.

Group II: Letrozole and temozolomideExperimental Treatment2 Interventions

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.

Group III: LetrozoleExperimental Treatment1 Intervention

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Letrozole

FDA approved

Temozolomide

2010

Completed Phase 3

~1880

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for brain tumors include chemotherapy, radiation therapy, and targeted molecular therapies. Chemotherapy agents like temozolomide work by damaging the DNA of cancer cells, leading to cell death. Radiation therapy uses high-energy particles to destroy cancer cells and shrink tumors. Targeted molecular therapies, such as bevacizumab, inhibit specific pathways involved in tumor growth and angiogenesis. Letrozole, an aromatase inhibitor, reduces estrogen levels, which may be beneficial in hormone-sensitive tumors. Understanding these mechanisms is crucial for brain tumor patients as it helps in selecting the most effective treatment based on the tumor's specific characteristics and molecular profile.

Extent of Resection Versus Molecular Classification: What Matters When?Bioinformatics analysis reveals potential candidate drugs for different subtypes of glioma.The combination of novel targeted molecular agents and radiation in the treatment of pediatric gliomas.