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

18 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination Fulvestrant and Abemaciclib for ovarian cancer?

Research shows that anti-estrogen therapy, like Fulvestrant, can be effective in some ovarian cancers, and identifying patients who might respond well could lead to better outcomes. Additionally, combining different therapies, as seen in other studies, often shows promise in treating ovarian cancer. ^{1 2 3 4 5}

Is the combination of Fulvestrant and Abemaciclib safe for humans?

The combination of Abemaciclib and Fulvestrant has been studied in breast cancer patients and is generally considered safe, with common side effects including diarrhea, infections, and low white blood cell counts. These side effects were mostly manageable. ^{6 7 8 9 10}

How is the drug combination of Fulvestrant and Abemaciclib unique for treating ovarian cancer?

The combination of Fulvestrant and Abemaciclib is unique because it involves a selective cyclin-dependent kinase 4 and 6 inhibitor (Abemaciclib) and an estrogen receptor degrader (Fulvestrant), which have shown effectiveness in hormone receptor-positive breast cancer. This approach may offer a novel mechanism for targeting ovarian cancer, especially if it shares similar hormone receptor characteristics. ^{7 8 9 11 12}

What is the purpose of this trial?

The goal of this clinical research study is to learn if fulvestrant and abemaciclib can help to control low-grade serous ovarian cancer. The safety of this drug combination will also be studied. This is an investigational study. Fulvestrant and abemaciclib are both FDA approved and commercially available for the treatment of several types of cancer. Their use in patients with low-grade serous ovarian cancer is investigational. The study doctor can explain how the study drugs are designed to work. Up to 15 participants will be enrolled in this study. All will take part at MD Anderson.

Research Team

Amir A. Jazaeri

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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.

I have advanced low-grade ovarian, peritoneal, or fallopian tube cancer and was advised to get therapy before surgery.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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 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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial. [2023]

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

Predicting response to the anti-estrogen fulvestrant in recurrent ovarian cancer. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Dual Fulvestrant-Trametinib Therapy in Recurrent Low-Grade Serous Ovarian Cancer. [2021]

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

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

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

Phase I trial of ribociclib with platinum chemotherapy in ovarian cancer. [2022]

6. United States 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. [2022]

7. France pubmed.ncbi.nlm.nih.gov

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

8. 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]

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

MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. [2022]

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

Abemaciclib: First Global Approval. [2019]

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

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

12. United States 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. [2022]