Exemestane for Endometrial Cancer

Recruiting at 4 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Hormone therapy, CYP3A4 inducers

Disqualifiers: Recent malignancies, Malabsorption, Hormone use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 3-6 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This pilot phase IIa trial studies how well exemestane works in treating patients with complex atypical hyperplasia of the endometrium/endometrial intraepithelial neoplasia or low grade endometrial cancer. Exemestane may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as hormone replacement therapy and strong CYP3A4 inducers like rifampicin and St. John's wort, at least 3 months before starting. If you're on any of these, you may need to stop them to participate.

What data supports the effectiveness of the drug exemestane for endometrial cancer?

Research shows that exemestane, a drug that lowers estrogen levels, has been effective in reducing symptoms and tumor markers in endometrial cancer patients. It has also been successful in treating breast cancer by improving disease-free survival, suggesting its potential benefit in other estrogen-sensitive cancers like endometrial cancer. ^{1 2 3 4 5}

Is exemestane safe for use in humans?

Exemestane, also known as Aromasin, has been shown to be generally safe and well-tolerated in humans, particularly in postmenopausal women with advanced breast cancer. Common mild side effects include hot flushes, nausea, and fatigue, and serious side effects are rare. ^{2 6 7 8 9}

How does the drug exemestane differ from other treatments for endometrial cancer?

Exemestane is unique because it is a steroidal aromatase inactivator, which means it permanently blocks the enzyme responsible for estrogen production, potentially reducing estrogen levels more effectively than non-steroidal inhibitors. This approach is novel for endometrial cancer, as it has primarily been used in breast cancer treatment. ^{1 2 3 6 9}

Research Team

Britt K Erickson

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

This trial is for postmenopausal women with complex atypical hyperplasia or low grade endometrial cancer who haven't had prior treatments. Participants must have adequate organ function, no recent invasive malignancies except certain skin cancers, not be on hormone therapy or strong CYP3A4 inducers, and able to take oral medications.

Inclusion Criteria

Your white blood cell count is at least 3000 per microliter.

Your hemoglobin level is at least 9 grams per deciliter.

I am fully active and can carry on all pre-disease activities without restriction.

Exclusion Criteria

I had cancer treated with the intent to cure, and all treatments ended less than a year ago, except for skin cancer.

I am not scheduled for surgery within 43 days of starting the study drug.

You have a medical, psychiatric, or social condition that may make it difficult for you to follow the study requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive exemestane orally once daily over 21-42 days

3-6 weeks

Daily oral administration

Surgery

Participants undergo standard of care surgery between days 22-43

1 day

1 visit (in-person)

Follow-up

Participants with unresolved adverse events on day of surgery are followed up periodically

Up to 7 months

Treatment Details

Interventions

• Exemestane

Trial Overview The trial tests exemestane's effectiveness in treating specific endometrial conditions by blocking enzymes that promote cell growth. It includes a pharmacokinetic study to see how the body processes the drug, biomarker analysis, and questionnaires.

Participant Groups

Group I: Treatment (exemestane) Experimental Treatment 4 Interventions

Patients receive exemestane PO QD over 21-42 days in the absence of disease progression or unaccepted toxicity. Patients undergo standard of care surgery between days 22-43.

Exemestane is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Aromasin for:

• Early breast cancer
• Advanced breast cancer

Approved in United States as Aromasin for:

• Early breast cancer
• Advanced breast cancer

Approved in Canada as Aromasin for:

• Early breast cancer
• Advanced breast cancer

Approved in Japan as Aromasin for:

• Early breast cancer
• Advanced breast cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Exemestane effectively suppresses aromatase and plasma estrogen levels in postmenopausal women with recurrent breast cancer, showing significant efficacy even in patients who have failed other treatments like tamoxifen and other aromatase inhibitors.

The drug has a favorable safety profile with mild toxicity primarily consisting of menopausal symptoms, and it has demonstrated an early survival advantage over megestrol acetate in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exemestane: a novel aromatase inactivator for breast cancer. Jones, SA., Jones, SE.[2016]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Exemestane: a review of its use in postmenopausal women with breast cancer. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Examestane in advanced or recurrent endometrial carcinoma: a prospective phase II study by the Nordic Society of Gynecologic Oncology (NSGO). [2021]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Comparison of letrozole and exemestane used in non-adjuvant therapy of endometrial carcinoma]. [2018]

4. Singapore pubmed.ncbi.nlm.nih.gov

Effect of exemestane on the invasive growth of endometrial carcinoma HHUA cells. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Exemestane in the adjuvant treatment of breast cancer in postmenopausal women. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Exemestane: a novel aromatase inactivator for breast cancer. [2016]

7. England pubmed.ncbi.nlm.nih.gov

Exemestane in advanced breast cancer. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Safety, activity and estrogen inhibition by exemestane in postmenopausal women with advanced breast cancer: a phase I study. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Multicenter, phase II trial of exemestane as third-line hormonal therapy of postmenopausal women with metastatic breast cancer. Aromasin Study Group. [2017]