Abemaciclib for Recurrent Ovarian or Endometrial Cancer

Overseen By Kimberly Kelly

Age: Any Age

Sex: Female

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Second malignancy, Heart conditions, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 16

Duration: 16 weeks

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of abemaciclib, a cancer treatment drug, for ovarian or endometrial cancer that has recurred and involves a specific cell growth pathway. Abemaciclib blocks certain enzymes that cancer cells need to grow. Participants must have recurrent ovarian or endometrial cancer with specific genetic features and must have already undergone chemotherapy. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use certain drugs that strongly affect liver enzymes (like grapefruit juice or some antibiotics). There is a required break of at least 21 days after chemotherapy and 14 days after radiotherapy before starting the trial.

Is there any evidence suggesting that abemaciclib is likely to be safe for humans?

Research has shown that abemaciclib, a drug tested for recurring ovarian or endometrial cancer, is generally well-tolerated. In earlier studies, patients taking abemaciclib, sometimes with hormone therapy, reported common side effects such as diarrhea, tiredness, and nausea. However, these side effects were usually manageable and did not prevent most patients from continuing treatment.

The FDA has already approved abemaciclib for treating breast cancer, which supports its safety profile. Patients in studies demonstrated that it can be taken safely, though monitoring for side effects remains important. While abemaciclib has shown safety in other cases, each person's experience with the treatment may vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ovarian or endometrial cancer?

Abemaciclib is unique because it specifically targets cyclin-dependent kinases 4 and 6 (CDK4/6), which are crucial for cancer cell growth. Unlike standard chemotherapy for recurrent ovarian or endometrial cancer, which often attacks both healthy and cancerous cells, abemaciclib focuses on disrupting the cancer cells' cycle, potentially leading to fewer side effects. Additionally, for patients with hormone receptor-positive tumors, combining abemaciclib with hormone therapies like anastrozole or letrozole could enhance its effectiveness, offering a tailored approach to treatment. Researchers are excited about abemaciclib because it represents a more targeted and potentially less toxic option compared to traditional treatments.

What evidence suggests that abemaciclib might be an effective treatment for recurrent ovarian or endometrial cancer?

Research has shown that abemaciclib can help treat certain types of recurring ovarian and endometrial cancers. Abemaciclib blocks specific enzymes that cancer cells need to grow, targeting the CDK4/6 pathway, which is often active in these cancers. In this trial, participants will receive abemaciclib, and those with hormone receptor-positive tumors will also receive hormonal therapy with anastrozole or letrozole per standard care. Studies have found that combining abemaciclib with hormonal therapy yields promising results, especially in patients with low-grade serous ovarian cancer and endometrioid endometrial cancer. One study showed this combination treatment had a response rate of over 25%. Additionally, after 24 weeks, 12.5% of patients with high-grade serous ovarian cancer and 50% of those with endometrioid endometrial cancer had not seen their cancer progress. This suggests that abemaciclib, particularly when combined with hormonal treatments, could help slow the progression of these cancers. ^{1 2 5 6 7}

Who Is on the Research Team?

Gottfried Konecny, MD

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with recurrent ovarian or endometrial cancer that has shown CDK4/6 pathway activation. Participants must have had at least one prior chemotherapy regimen, be able to swallow pills, and meet specific blood count criteria. They should not have other recent cancers or major health issues like unstable heart disease, infections requiring IV antibiotics, or certain mental conditions.

Inclusion Criteria

My ovarian cancer has been tested and shows CDK4/6 activation.

Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN

Exclusion Criteria

I am not willing to use effective birth control methods.

I do not have unstable brain tumors or cancer in the lining of my brain.

I do not expect to need major surgery or radiation therapy during the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abemaciclib orally twice daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

16 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib

Trial Overview The effectiveness of abemaciclib in treating recurrent ovarian and endometrial cancer is being tested. This drug aims to halt tumor growth by inhibiting enzymes necessary for cell proliferation. The study will determine if abemaciclib improves treatment outcomes for these cancers.

How Is the Trial Designed?

Group I: Treatment (abemaciclib) Experimental Treatment 3 Interventions

Patients receive abemaciclib PO BID on days 1-28. Patients with tumors that are hormone receptor positive also receive and anastrozole or letrozole per standard of care. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

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

Published Research Related to This Trial

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]

Abemaciclib is an oral medication that inhibits cyclin-dependent kinases 4 and 6, specifically approved in the USA for treating advanced or metastatic breast cancer that is hormone receptor-positive and HER2-negative.

It is effective both as a combination therapy with fulvestrant for patients who have progressed after endocrine therapy and as a standalone treatment for those who have also undergone chemotherapy, highlighting its role in advanced cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: First Global Approval. Kim, ES.[2019]

Recent advancements in treating epithelial ovarian cancer (EOC) include the use of antiangiogenic drugs like Bevacizumab and PARP inhibitors (olaparib, niraparib, rucaparib), which have shown to improve progression-free survival (PFS) and initial overall survival (OS) in patients.

To enhance treatment outcomes, implementing biobanking and analyzing tumor samples before treatment could help identify predictive markers and optimize the use of experimental drugs, including immunomodulators and targeted therapies, for better management of recurrent ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of new medical treatment for epithelial ovarian cancer recurrence. Mancari, R., Cutillo, G., Bruno, V., et al.[2020]

Poly(ADP-ribose) polymerase inhibitors (PARPi) have been rapidly developed and approved for treating BRCA-associated ovarian cancer, with three different PARPi (niraparib, olaparib, and rucaparib) receiving multiple approvals since 2014 for various treatment settings, including maintenance therapy after platinum-based chemotherapy.

PARPi can be used as monotherapy or in combination with other treatments like bevacizumab, showing efficacy in both frontline and recurrent settings, and ongoing trials are exploring ways to enhance their effectiveness, especially in tumors that do not have specific biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poly(ADP-Ribose) Polymerase Inhibitor Inhibition in Ovarian Cancer: A Comprehensive Review. Moore, KN., Pothuri, B.[2022]

A 50-year-old woman with stage IVB poorly differentiated endometrial cancer experienced a significant clinical complete response after receiving the PARP inhibitor Olaparib, following the identification of a BRIP1 mutation.

This case represents the first documented instance of a pathologic complete response in high-grade endometrioid endometrial cancer treated with a PARP inhibitor, highlighting the potential for targeted therapies in cases with specific genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete Pathologic Response to PARP Inhibitor Olaparib in a Patient with Stage IVB Recurrent Endometrioid Endometrial Adenocarcinoma. Senguttuvan, RN., Wei, C., Raoof, M., et al.[2023]

Olaparib, a PARP inhibitor, showed a 36% objective response rate in women with relapsed ovarian cancer and a germline BRCA1/2 mutation, even after they had undergone multiple lines of chemotherapy, indicating its efficacy in this challenging patient population.

The median duration of response to olaparib was 7.4 months, and the safety profile was consistent across patients who had received three or more lines of prior chemotherapy, with similar rates of serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Matulonis, UA., Penson, RT., Domchek, SM., et al.[2022]

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]

A 32-year-old woman with recurrent ovarian clear cell carcinoma (OCCC) showed a partial response to a novel treatment combining olaparib (a PARP inhibitor), pembrolizumab (a PD-1 inhibitor), and bevacizumab (an antiangiogenic agent), which was sustained for 12 months.

This case highlights the potential effectiveness of this triplet therapy for patients with platinum-resistant, recurrent OCCC, especially in the context of identified genomic mutations like ARID1A and homologous recombination deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remarkable Response to the Triplet Combination of Olaparib with Pembrolizumab and Bevacizumab in the Third-Line Treatment of an Ovarian Clear Cell Carcinoma Patient with an ARID1A Mutation: A Case Report. Zhao, Y., Jiang, Y.[2022]

Adjuvant chemotherapy with platinum-based combinations, specifically carboplatin plus paclitaxel, is the standard treatment for early-stage high-grade serous and endometrioid carcinomas, while neoadjuvant chemotherapy is considered on a case-by-case basis.

Recent studies have shown that PARP inhibitors (PARPi) significantly improve progression-free survival in patients with high-grade ovarian carcinoma, particularly those with BRCA mutations or homologous recombination DNA repair deficiencies, making them important options for maintenance therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Traitement médical de première ligne du cancer épithélial de l'ovaire de haut grade: First-line medical treatment of high-grade epithelial ovarian cancer. Selle, F., Alexandre, J., Prulhière, K., et al.[2022]

In the nextMONARCH study involving women with endocrine-refractory HR+, HER2- metastatic breast cancer, abemaciclib showed a median progression-free survival (PFS) of 9.1 months when combined with tamoxifen, but this was not significantly better than the 7.4 months PFS with abemaciclib alone plus prophylactic loperamide.

The study found that the incidence and severity of diarrhea, a common side effect of abemaciclib, were manageable with dose adjustments and antidiarrheal medication, indicating that the treatment can be tolerated while maintaining its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nextMONARCH: Abemaciclib Monotherapy or Combined With Tamoxifen for Metastatic Breast Cancer. Hamilton, E., Cortes, J., Ozyilkan, O., et al.[2021]

Olaparib, approved by the FDA for patients with advanced ovarian cancer carrying BRCA mutations, showed a 34% objective response rate in a trial of 137 patients who had undergone three or more prior chemotherapy treatments, with a median response duration of 7.9 months.

Common side effects included anemia, nausea, and fatigue, with a small risk (2%) of developing myelodysplastic syndrome or acute myeloid leukemia, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with Three or More Lines of Chemotherapy. Kim, G., Ison, G., McKee, AE., et al.[2022]

Recent advancements in ovarian cancer treatment have introduced several new options that show improved survival rates compared to historical data, marking a significant progress after decades of stagnation.

Three new PARP inhibitors (olaparib, rucaparib, niraparib) have been approved for ovarian cancer, providing new maintenance and recurrence treatment options, alongside expanded uses for bevacizumab in combination chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Therapies for Ovarian Cancer. O'Malley, DM.[2020]

A 42-year-old woman with a BRCA2 mutation and recurrent low-grade endometrial cancer showed positive clinical and radiographic responses to the PARP inhibitor olaparib, indicating its potential efficacy in this specific patient population.

This case highlights the importance of genetic factors, such as BRCA2 mutations, in determining the effectiveness of targeted therapies like olaparib for treating certain types of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durable response in a woman with recurrent low-grade endometrioid endometrial cancer and a germline BRCA2 mutation treated with a PARP inhibitor. Gockley, AA., Kolin, DL., Awtrey, CS., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04469764

Study Details | NCT04469764 | Abemaciclib for the ... This phase II trial studies how well abemaciclib works in treating patients with ovarian or endometrial cancer that has an activation of the CDK4/6 pathway ...

2. cancernetwork.com cancernetwork.com/view/abemaciclib-plus-hormonal-therapy-shows-promising-efficacy-in-lgsoc-eec

Abemaciclib Plus Hormonal Therapy Shows Promising ... Abemaciclib (Verzenio) plus hormonal therapy demonstrated clinical activity in patients with recurrent low-grade serous ovarian cancer (LGSOC) and endometrioid ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10982620/

A phase II, multicenter, open-label study of abemaciclib and ... The combination therapy of abemaciclib and letrozole will provide a clinically meaningful therapeutic benefit, with an overall response rate of >25%.

4. onclive.com onclive.com/view/dr-silverstein-on-the-efficacy-of-abemaciclib-plus-hormonal-therapy-in-recurrent-low--or-high-grade-serous-ovarian-cancer

or High-Grade Serous Ovarian Cancer In those with high-grade serous ovarian cancer and endometrioid endometrial cancer, the 24-week PFS rates were 12.5% and 50.0%. Despite ...

5. withpower.com withpower.com/trial/phase-3-endometrial-neoplasms-9-2020-12c64

Abemaciclib for Recurrent Ovarian or Endometrial Cancer A study on endometrial cancer showed that Abemaciclib, when combined with another drug called letrozole, may be effective due to its ability to interfere with ...

6. gynecologiconcology-online.net gynecologiconcology-online.net/article/S0090-8258(25)00314-2/abstract

Efficacy and safety of abemaciclib, a CDK4/6 inhibitor ... Efficacy and safety of abemaciclib, a CDK4/6 inhibitor, combined with hormone therapy in selected patients with recurrent ovarian or endometrial cancer: An open ...

7. trialx.com trialx.com/clinical-trials/listings/247136/abemaciclib-for-the-treatment-of-recurrent-ovarian-or-endometrial-cancer/

Abemaciclib for the Treatment of Recurrent Ovarian or ... Overview. This phase II trial studies how well abemaciclib works in treating patients with ovarian or endometrial cancer that has an ...