Fulvestrant + Abemaciclib for Ovarian Cancer

Overseen By Ljiljiana Milojevic

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Goserelin

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Pregnancy, HIV, Hepatitis, 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: 32

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether two drugs, fulvestrant and abemaciclib, can help control low-grade serous ovarian cancer. Both drugs are already used for other cancers, but their effectiveness for this specific type remains under study. The trial also examines the safety of using these drugs together. Women with advanced stages of this cancer who are not expected to benefit from surgery might be suitable candidates. Conducted at MD Anderson, the study includes up to 15 participants. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will 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 drugs that are potent CYP3A4 inhibitors or inducers, or drugs that prolong the QT interval. It's best to discuss your current medications with the study doctor.

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

Past studies have shown that the combination of fulvestrant and abemaciclib is well-tolerated. Research indicates that this combination has been used safely in people with breast cancer. The treatment helped many patients without causing major side effects. Some patients experienced mild to moderate reactions like tiredness or diarrhea, but these were manageable. Both fulvestrant and abemaciclib have FDA approval for other types of cancer, indicating thorough safety testing. While their use for low-grade serous ovarian cancer is new, their past safety record is reassuring. ^{1 2 3 4 5}

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

Fulvestrant + Abemaciclib is unique because it combines two powerful treatments that work together to fight ovarian cancer. Unlike traditional chemotherapy, which attacks all fast-growing cells, this combination targets specific proteins involved in cancer cell growth. Fulvestrant blocks estrogen receptors, while Abemaciclib inhibits CDK4/6 proteins, which are crucial for cell division. Researchers are excited about this approach because it offers a more targeted attack on cancer cells, potentially leading to fewer side effects and improved outcomes for patients.

What evidence suggests that fulvestrant and abemaciclib might be an effective treatment for low-grade serous ovarian cancer?

Research has shown that using fulvestrant and abemaciclib together may help treat certain cancers. One study found that patients taking both drugs had their cancer remain controlled for an average of 16.4 months, compared to 9.3 months for those taking only fulvestrant. This indicates that patients experienced a longer period without cancer progression. Another study reported similar results, with the combination extending the time to 16.9 months. These findings suggest that using both drugs together might be more effective than using just one for certain cancers. This trial will specifically evaluate the combination of fulvestrant and abemaciclib for ovarian cancer, building on the positive results seen in other cancers. ^{1 2 3 4 5}

Who Is on the Research Team?

Amir A. Jazaeri

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for women over 18 with advanced low-grade serous ovarian, primary peritoneal, or fallopian tube carcinomas who have measurable disease and are recommended to receive neoadjuvant therapy. Participants must be in good physical condition (ECOG PS 0-1), not pregnant, willing to use birth control, and able to undergo a biopsy. They should not have received prior treatment for ovarian cancer.

Inclusion Criteria

I agree to give tissue samples before and after treatment for research.

My cancer diagnosis was confirmed with a biopsy, not just a needle aspiration.

Women of child-bearing potential must have a negative serum or urine human chorionic gonadotropin (HCG) test within 72 hours prior to receiving the first dose of study medication

Exclusion Criteria

I have had chemotherapy or hormonal therapy for ovarian cancer.

I have been diagnosed with Hepatitis B, C, or HIV.

I am pre or perimenopausal and allergic to certain hormone treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive fulvestrant and abemaciclib before surgery for 4 cycles

16 weeks

Visits on Days 1 and 15 of Cycle 1, and Day 1 of Cycles 2-4

Surgery

Participants undergo scheduled surgery as part of standard care

1 day

Adjuvant Treatment

Participants receive fulvestrant and abemaciclib after surgery for cycles 5 and beyond

Ongoing

Visits on Day 1 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

30-day follow-up phone call

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Fulvestrant

Trial Overview The study tests the effectiveness of fulvestrant combined with abemaciclib in controlling low-grade serous ovarian cancer. Both drugs are FDA approved for other cancers but their combination is investigational here. All participants at MD Anderson will receive this drug combo and provide tissue samples for research.

How Is the Trial Designed?

Group I: Fulvestrant + Abemaciclib Experimental Treatment 2 Interventions

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In the MONARCH 2 study involving 669 women with advanced breast cancer, the combination of abemaciclib and fulvestrant significantly improved progression-free survival (PFS) to a median of 16.4 months compared to 9.3 months with fulvestrant alone.

The combination therapy also achieved a higher objective response rate (ORR) of 48.1% versus 21.3% in the control group, while maintaining a tolerable safety profile, with common side effects including diarrhea and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. Sledge, GW., Toi, M., Neven, P., et al.[2022]

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]

In the MONARCH 2 study, abemaciclib combined with fulvestrant significantly improved progression-free survival (PFS) and overall survival (OS) in patients with hormone receptor positive, HER2-negative advanced breast cancer, showing consistent benefits across both first-line and second-line treatment groups.

The most substantial benefits were seen in patients with primary resistance to endocrine therapy and those with visceral disease, indicating that abemaciclib may be particularly effective for these subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 2: Subgroup Analysis of Patients Receiving Abemaciclib Plus Fulvestrant as First-Line and Second-Line Therapy for HR+, HER2--Advanced Breast Cancer. Neven, P., Johnston, SRD., Toi, M., 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]

In a phase III study involving 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer, abemaciclib significantly improved progression-free survival compared to placebo, with a hazard ratio of 0.54, indicating a strong efficacy as initial therapy.

The most common side effect of abemaciclib was diarrhea, occurring in 81.3% of patients, but most cases were mild (grade 1), suggesting that while there are some adverse effects, the treatment has a tolerable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. Goetz, MP., Toi, M., Campone, M., 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]

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]

In a phase I trial involving 35 patients with recurrent platinum-sensitive ovarian cancer, the combination of ribociclib with carboplatin and paclitaxel chemotherapy was found to be safe, with a maximum tolerated dose of 400 mg.

The treatment showed a high overall response rate of 79.3% and a clinical benefit rate of 96.6%, with a median progression-free survival of 11.4 months, indicating promising initial efficacy for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of ribociclib with platinum chemotherapy in ovarian cancer. Coffman, LG., Orellana, TJ., Liu, T., et al.[2022]

Citations

1. 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 ...

2. lbbc.org lbbc.org/news/abemaciclib-shows-small-benefit-after-a-prior-cdk-4-6-inhibitor-stops-working-asco-2024

Abemaciclib shows small benefit after a prior CDK 4/6 ... The phase III clinical trial showed that abemaciclib (Verzenio) plus fulvestrant (Faslodex) was more effective than fulvestrant alone after a prior anti-CDK 4/ ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6296414/

Combination Therapies in Advanced, Hormone Receptor– ... Patients treated with the fulvestrant and abemaciclib combination achieved a median PFS of 16.4 months compared with 9.3 months in the fulvestrant monotherapy ...

4. onclive.com onclive.com/view/avutometinib-abemaciclib-fulvestrant-combo-is-active-safe-in-cdk4-6-inhibitor-resistant-hr-her2-metastatic-breast-cancer

Avutometinib/Abemaciclib/Fulvestrant Combo Is Active ... Preliminary efficacy results included a 13.3% overall response rate and a 46.7% stable disease rate, with a median progression-free survival of ...

5. oncpracticemanagement.com oncpracticemanagement.com/special-issues/the-evolution-of-abemaciclib-clinical-trial-data-for-the-treatment-of-hr-positive-her2-negative-metastatic-breast-cancer

The Evolution of Abemaciclib Clinical Trial Data for ... Efficacy. PFS was significantly improved with the combination of abemaciclib plus fulvestrant of 16.9 months compared with 9.3 months with fulvestrant ...