Abemaciclib for Recurrent Ovarian or Endometrial Cancer

Overseen by Gottfried Konecny, MD

Age: Any Age

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Second malignancy, Heart conditions, Infections, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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 and that has come back (recurrent). Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving abemaciclib may work better for the treatment of recurrent ovarian and endometrial cancer.

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.

What data supports the effectiveness of the drug 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 cancer cell growth by targeting specific pathways involved in cell cycle progression. ^{1 2 3 4 5}

Is Abemaciclib safe for humans?

Abemaciclib has been used in treating breast cancer and is generally considered safe, with common side effects including diarrhea, infections, and low white blood cell counts. It has been studied in combination with other therapies and has a manageable safety profile. ^{3 6 7 8 9}

How is the drug Abemaciclib unique for treating recurrent ovarian or endometrial cancer?

Abemaciclib is unique because it is a CDK4/6 inhibitor, which works by blocking proteins that promote cancer cell growth, offering a different mechanism of action compared to other treatments like PARP inhibitors or chemotherapy, which are commonly used for these cancers. ^{1 10 11 12 13}

Research Team

Gottfried Konecny, MD

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Abemaciclib (CDK4/6 Inhibitor)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Dr. Aparna Bhaduri

Jonsson Comprehensive Cancer Center

Chief Medical Officer since 2024

MD

Dr. Michael A. Teitell

Jonsson Comprehensive Cancer Center

Chief Executive Officer since 2024

MD, PhD

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

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 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]

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]

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]

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 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]

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]

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]

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]

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]

References

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

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

2. New Zealand 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. [2022]

3. 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]

4. England 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. [2022]

5. France 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. [2022]

6. France pubmed.ncbi.nlm.nih.gov

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

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

Abemaciclib: First Global Approval. [2019]

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

nextMONARCH: Abemaciclib Monotherapy or Combined With Tamoxifen for Metastatic Breast Cancer. [2021]

9. United States 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. [2022]

10. United States 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. [2018]

11. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Development of new medical treatment for epithelial ovarian cancer recurrence. [2020]

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

New Therapies for Ovarian Cancer. [2020]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Complete Pathologic Response to PARP Inhibitor Olaparib in a Patient with Stage IVB Recurrent Endometrioid Endometrial Adenocarcinoma. [2023]