Abemaciclib + Letrozole for Endometrial Cancer

Recruiting at 31 trial locations

Overseen By Jennifer Klein, MEd

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Gynecologic Oncology Group

Must not be taking: CDK4/6 inhibitors, Hormonal therapy, Steroids, Immunosuppressants

Disqualifiers: Other malignancies, Cardiac disease, Active infections, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

53 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase II single arm trial to determine the percentage of patients without evidence of disease progression on abemaciclib and letrozole in advanced stage, persistent or recurrent endometrioid endometrial cancer at 6 months. Treatment will continue until either unacceptable toxicity, progression of disease, or investigator/patient request for withdrawal.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of at least 21 days after the last dose of any previous systemic therapy before starting the trial treatment. If you are on systemic steroids or immunosuppressive agents, you may need to stop them, as they are not allowed during the trial.

What data supports the effectiveness of the drug combination Abemaciclib and Letrozole for endometrial cancer?

Research suggests that the combination of Abemaciclib and Letrozole may be effective for endometrial cancer because Abemaciclib has shown benefits in breast cancer by reducing cancer recurrence when combined with endocrine therapy, and Letrozole has been studied for its hormonal effects in endometrial cancer. ^{1 2 3 4 5}

Is the combination of Abemaciclib and Letrozole safe for humans?

Abemaciclib, when combined with endocrine therapy like Letrozole, has been found to have an acceptable and manageable safety profile in breast cancer patients, with common side effects including diarrhea, infections, and neutropenia (low white blood cell count). ^{1 2 3 4 5}

How is the drug combination of Abemaciclib and Letrozole unique for treating endometrial cancer?

The combination of Abemaciclib and Letrozole is unique for treating endometrial cancer because it targets both the estrogen receptor and cell cycle pathways, which are often altered in these cancers. This dual approach may help overcome resistance to hormonal therapy and improve treatment effectiveness. ^{1 2 3 4 6}

Research Team

Marilyn Huang, MD

Principal Investigator

University of Virginia

Eligibility Criteria

This trial is for adults with advanced, persistent, or recurrent endometrioid endometrial cancer that can't be cured by surgery or radiotherapy. Participants must have measurable disease, no more than two prior systemic therapies (only one may include chemo), and good organ function. They cannot join if they've had CDK4/6 inhibitors before, other cancer types like clear cell or serous cancers, known allergies to the drugs being tested, active infections, CNS metastases, HIV infection, certain medical conditions affecting drug absorption or bleeding risk.

Inclusion Criteria

I've had chemotherapy for early-stage cancer or for a pelvic recurrence.

My cancer's MMR, MSI, and hormone receptor status have been tested and reported if available.

My cancer is endometrioid type, confirmed by surgery or biopsy.

Exclusion Criteria

I have taken medication that targets CDK4/6 for my cancer.

My cancer has spread to my brain.

I do not have any ongoing serious infections.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abemaciclib and letrozole until unacceptable toxicity, disease progression, or withdrawal

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 5 years

Treatment Details

Interventions

• Abemaciclib
• Letrozole

Trial Overview The trial tests how well patients with specific endometrial cancer respond to a combination of Abemaciclib and Letrozole after six months without their disease getting worse. It's a phase II study where all participants receive the same treatment until it's not tolerated anymore or until the disease progresses.

Participant Groups

Group I: Abemaciclib and Letrozole Experimental Treatment 2 Interventions

Study treatment will consist of abemaciclib 150mg orally twice a day and letrozole 2.5mg orally once a day.

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Who Is Running the Clinical Trial?

Gynecologic Oncology Group

Lead Sponsor

Trials

251

Recruited

65,400+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

In a study of 10 post-menopausal patients with endometrial cancer, short-term treatment with letrozole was well-tolerated and led to a significant 37.8% reduction in blood estradiol levels, indicating its effectiveness in lowering estrogen levels.

The treatment also resulted in notable clinical improvements, such as pain relief and a 31.1% decrease in endometrial ultrasound signal, suggesting potential benefits in managing endometrial cancer before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant therapy of endometrial cancer with the aromatase inhibitor letrozole: endocrine and clinical effects. Berstein, L., Maximov, S., Gershfeld, E., et al.[2019]

In a phase II study involving 30 patients with recurrent ER-positive endometrial cancer, the combination of letrozole and abemaciclib showed a 30% objective response rate, indicating promising efficacy in treating this type of cancer.

The treatment resulted in a median progression-free survival of 9.1 months, with 55.6% of patients remaining progression-free at 6 months, while the most common serious side effects were neutropenia and anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II, Two-Stage Study of Letrozole and Abemaciclib in Estrogen Receptor-Positive Recurrent Endometrial Cancer. Konstantinopoulos, PA., Lee, EK., Xiong, N., et al.[2023]

In a phase III trial, abemaciclib combined with endocrine therapy significantly reduced the risk of breast cancer recurrence in patients with hormone receptor positive (HR+), HER2-negative, node-positive early breast cancer, regardless of prior chemotherapy or tumor characteristics.

The combination treatment was generally well-tolerated, with manageable side effects such as diarrhea, infections, and neutropenia, making it a valuable option for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. Fung, S., Blair, HA.[2023]

In a pooled analysis of 1152 patients from the MONARCH 2 and MONARCH 3 studies, abemaciclib combined with endocrine therapy showed a consistent improvement in progression-free survival (PFS) across all age groups, indicating its efficacy in treating HR+, HER2- advanced breast cancer regardless of age.

Older patients experienced higher rates of clinically relevant side effects, such as diarrhea and nausea, but these were manageable with dose adjustments, suggesting that while safety concerns exist, the treatment remains effective for older populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of abemaciclib plus endocrine therapy in older patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: an age-specific subgroup analysis of MONARCH 2 and 3 trials. Goetz, MP., Okera, M., Wildiers, H., et al.[2022]

Interim results from the MONARCH3 study show that abemaciclib, a CDK4/6 inhibitor, is an effective first-line treatment for advanced ER-positive, HER2-negative breast cancer.

Patients receiving abemaciclib in combination with letrozole experienced significantly improved progression-free survival compared to those receiving a placebo with endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant therapy of endometrial cancer with the aromatase inhibitor letrozole: endocrine and clinical effects. [2019]

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

A Phase II, Two-Stage Study of Letrozole and Abemaciclib in Estrogen Receptor-Positive Recurrent Endometrial Cancer. [2023]

3. France pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and efficacy of abemaciclib plus endocrine therapy in older patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: an age-specific subgroup analysis of MONARCH 2 and 3 trials. [2022]

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

First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Use of estrogen antagonists and aromatase inhibitors in breast cancer and hormonally sensitive tumors of the uterine body. [2007]