Endocrine Therapy + CDK4/6 Inhibitor for Breast Cancer

Recruiting at 1 trial location

Overseen By Hopkins Breast Trials

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must be taking: Endocrine therapy, Palbociclib

Disqualifiers: Pregnancy, Nursing, Recent malignancy, 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

Compensation: Varies

Number of Visits: 4

Duration: 3 years

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, premenopausal women and men must take a luteinizing hormone-releasing hormone (LHRH) agonist alongside the trial treatment.

What data supports the effectiveness of the drug combination of endocrine therapy and CDK4/6 inhibitors for breast cancer?

Research shows that adding CDK4/6 inhibitors like abemaciclib, palbociclib, or ribociclib to hormone therapy significantly improves outcomes for patients with certain types of advanced breast cancer, helping them live longer without the disease getting worse. These drugs are now a standard treatment option for hormone receptor-positive, HER2-negative breast cancer. ^{1 2 3 4 5}

Is the combination of endocrine therapy and CDK4/6 inhibitors safe for breast cancer treatment?

The combination of endocrine therapy and CDK4/6 inhibitors like abemaciclib, palbociclib, and ribociclib is generally considered safe, but it can cause side effects such as diarrhea and other adverse events. These treatments have been shown to have a manageable safety profile in clinical trials for breast cancer. ^{2 6 7 8 9}

How is the drug combination of CDK4/6 inhibitors and endocrine therapy unique for breast cancer treatment?

The combination of CDK4/6 inhibitors (like abemaciclib, palbociclib, and ribociclib) with endocrine therapy is unique because it significantly improves progression-free survival and response rates in hormone receptor-positive, HER2-negative metastatic breast cancer compared to endocrine therapy alone, and has become a new standard of care. ^{2 4 8 10 11}

What is the purpose of this trial?

The goal of this research study is to determine if the investigators can predict which participants will respond to endocrine therapy and a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor for metastatic breast cancer and which participants will not. Investigators will use information from the tumor tissue and serial blood samples. Investigators hope that a deeper understanding of which participants will respond to this combination and how resistance emerges will allow the investigators to better tailor therapies for metastatic breast cancer. Subjects will have archived tissue or new biopsy collected at study enrollment. This tissue will undergo special molecular testing. Subjects will also have blood collected at study enrollment and periodically thereafter. This blood will also undergo special molecular testing. Information from this testing will not be available to subjects or their treating physicians as the investigators do not know how this information should impact treatment. The investigators will collect information about which treatment the subjects receive and how their cancer responds. Any man or woman being seen at Johns Hopkins for treatment of newly diagnosed estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+) metastatic breast cancer may be eligible.

Research Team

Jessica Tao

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for men and women over 18 with newly diagnosed ER+/PR+ metastatic or advanced breast cancer, who are treatment-naive or on their first-line therapy with endocrine therapy and palbociclib. Participants must not be pregnant, nursing, or have had another primary cancer in the last 5 years (except certain skin cancers).

Inclusion Criteria

Ability to give voluntary informed consent

I have tissue from a metastatic site collected in the last 6 months.

I am about to start or am currently on my first treatment with ET and palbociclib for advanced cancer.

Exclusion Criteria

I haven't had any other cancers in the last 5 years, except for skin cancer or in situ cancer.

Any pregnant or nursing woman

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive endocrine therapy and a CDK4/6 inhibitor, with blood collections at initiation, 4 weeks, and every 3-4 months

3 years

Initial visit, 4-week visit, then every 3-4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with focus on genetic mutations at progression

4 weeks

Treatment Details

Interventions

• CDK4/6 Inhibitor
• Endocrine Therapy

Trial Overview Researchers are testing if they can predict who will respond to endocrine therapy combined with a CDK4/6 inhibitor for treating metastatic breast cancer by analyzing tumor tissue and blood samples. The study aims to personalize future therapies based on these predictions.

Participant Groups

Group I: Cohort B: Participants initiating a CDK 4/6 i after progression on ET. Experimental Treatment 1 Intervention

Participants will undergo blood collection (intervention) at time of initiating treatment with endocrine therapy and palbociclib, at 4 weeks after initiating this treatment, and every 3-4 months while on treatment. If a participant progresses on this treatment, they will have a blood collection at that time.

Group II: Cohort A: Participants with untreated metastatic disease receiving ET and a CDK 4/6 Experimental Treatment 1 Intervention

Participants will undergo blood collection (intervention) at time of initiating treatment with endocrine therapy and palbociclib, at 4 weeks after initiating this treatment, and every 3-4 months while on treatment. If a participant progresses on this treatment, they will have a blood collection at that time.

CDK4/6 Inhibitor is already approved in United States, European Union for the following indications:

Approved in United States as Abemaciclib (Verzenio) for:

• Hormone receptor-positive, HER2-negative metastatic breast cancer
• Early breast cancer

Approved in United States as Ribociclib (Kisqali) for:

• Hormone receptor-positive, HER2-negative metastatic breast cancer
• Early breast cancer

Approved in United States as Palbociclib (Ibrance) for:

• Hormone receptor-positive, HER2-negative metastatic breast cancer

Approved in European Union as Abemaciclib (Verzenio) for:

• Hormone receptor-positive, HER2-negative metastatic breast cancer
• Early breast cancer

Approved in European Union as Ribociclib (Kisqali) for:

• Hormone receptor-positive, HER2-negative metastatic breast cancer
• Early breast cancer

Approved in European Union as Palbociclib (Ibrance) for:

• Hormone receptor-positive, HER2-negative metastatic breast cancer

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Safeway Foundation

Collaborator

Trials

2

Recruited

100,000+

Biovica International AB

Collaborator

Trials

1

Recruited

100+

Findings from Research

Palbociclib has been approved for treating hormone receptor-positive advanced breast cancer due to its ability to improve progression-free survival when used with endocrine agents, highlighting its efficacy in this patient population.

Abemaciclib and ribociclib, two other CDK4/6 inhibitors, are in late-stage clinical development and may offer different benefits, such as single-agent activity and central nervous system penetration, which could influence treatment choices and patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Development of the CDK4/6 Inhibitors Ribociclib and Abemaciclib in Breast Cancer. Barroso-Sousa, R., Shapiro, GI., Tolaney, SM.[2020]

The addition of CDK4 and 6 inhibitors (like abemaciclib, palbociclib, or ribociclib) to endocrine therapy significantly improves progression-free survival and response rates in patients with HR+ and HER2- metastatic breast cancer, establishing these inhibitors as a new standard of care.

Exploratory analyses suggest that abemaciclib may be particularly beneficial for women with poor prognosis indicators, although further confirmation is needed for these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib, a CDK4 and CDK6 inhibitor for the treatment of metastatic breast cancer. Martin, M., Garcia-Saenz, JA., Manso, L., et al.[2021]

The study reviews the efficacy of three FDA-approved CDK4/6 inhibitors (Palbociclib, Ribociclib, and Abemaciclib) in treating advanced and metastatic hormone receptor-positive breast cancer, highlighting their potential to overcome endocrine resistance.

While these inhibitors show promise in HR+/HER2- breast cancer, the research aims to identify biomarkers that could predict their effectiveness in other breast cancer types, suggesting a need for tailored treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Latest Overview of the Cyclin-Dependent Kinases 4/6 Inhibitors in Breast Cancer: The Past, the Present and the Future. Chen, X., Xu, D., Li, X., et al.[2020]

Combination therapy using CDK4/6 inhibitors with endocrine therapy significantly reduces the risk of disease progression in hormone receptor-positive, ERBB2-negative advanced breast cancer, with randomized phase 3 studies showing about a 50% reduction in hazard risk compared to hormonal therapy alone.

While CDK4/6 inhibitors have shown clear benefits in overall survival in metastatic settings, there are emerging differences in efficacy and adverse effects among the inhibitors, highlighting the need for further research to optimize treatment sequencing and identify predictive biomarkers for patient response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclin-Dependent Kinase 4/6 Inhibitors for Treatment of Hormone Receptor-Positive, ERBB2-Negative Breast Cancer: A Review. O'Sullivan, CC., Clarke, R., Goetz, MP., et al.[2023]

CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) significantly improve progression-free survival in patients with hormone receptor-positive HER2-negative metastatic breast cancer when used alongside endocrine therapy, with a consistent hazard ratio of around 0.5 across phase III trials.

These treatments are generally well tolerated, with manageable side effects; however, abemaciclib is associated with a higher incidence of diarrhea, while palbociclib and ribociclib are more likely to cause hematological toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDK4/6 Inhibitors Expand the Therapeutic Options in Breast Cancer: Palbociclib, Ribociclib and Abemaciclib. Eggersmann, TK., Degenhardt, T., Gluz, O., et al.[2019]

CDK4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, have significantly improved treatment outcomes for hormone receptor-positive and HER2-negative breast cancer, establishing themselves as key options in both first- and second-line therapies.

While these inhibitors effectively prolong overall survival and progression-free survival in patients, they are also associated with notable adverse events, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Overview of the Safety Profile and Clinical Impact of CDK4/6 Inhibitors in Breast Cancer-A Systematic Review of Randomized Phase II and III Clinical Trials. Stanciu, IM., Parosanu, AI., Nitipir, C.[2023]

Abemaciclib, a recently approved CDK4/6 inhibitor, is effective for treating hormone-receptor-positive breast cancer, which is the most common subtype of breast cancer.

The oral administration and manageable side effects of abemaciclib make it a favorable option for patients, highlighting its potential role in both current and future breast cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of abemaciclib and its potential in the treatment of breast cancer. Martin, JM., Goldstein, LJ.[2020]

Abemaciclib, a CDK4/6 inhibitor, has been shown to significantly improve progression-free survival in patients with endocrine-receptor positive metastatic breast cancer, establishing it as a new standard of care alongside endocrine therapy.

The drug has a safe and manageable toxicity profile, but ongoing research is focused on identifying biomarkers to better select patients who will benefit from CDK4/6 inhibitors and exploring combination therapies to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic drug evaluation of abemaciclib for advanced breast cancer. Robert, M., Frenel, JS., Bourbouloux, E., et al.[2019]

In a study of 80 women with advanced breast cancer, factors such as being 70 years or older, taking multiple medications, and having gastrointestinal diseases were significantly associated with a higher risk of experiencing grade 2/3 diarrhea when treated with abemaciclib plus endocrine therapy.

The study's model demonstrated 82% sensitivity and 75% specificity in predicting diarrhea risk, suggesting that identifying these risk factors can help in implementing preventive strategies to manage abemaciclib's gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib-associated Diarrhea: An Exploratory Analysis of Real-life Data. Gebbia, V., Martorana, F., Sanò, MV., et al.[2023]

CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) have shown positive results in clinical trials for treating estrogen receptor positive (ER+)/HER2-negative metastatic breast cancer, indicating a shift in treatment strategies.

These inhibitors work by targeting key kinases that promote cancer cell proliferation, leading to improved outcomes and potentially better quality of life for patients compared to traditional sequential endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical development of CDK4/6 inhibitor for breast cancer. Iwata, H.[2019]

CDK4/6 inhibitors, when used with aromatase inhibitors or fulvestrant, provide an effective treatment option for hormone receptor-positive, HER2-negative breast cancer patients, leading to longer progression-free survival.

In a two-year clinical experience study, the side effects and tumor responses to palbociclib and ribociclib were consistent with existing data, indicating their promising role in breast cancer therapy, although the choice of aromatase inhibitor may influence outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First clinical experience with CDK4/6 inhibitors in breast cancer therapy. Cobec, IM., Moleriu, L., Moatar, AE., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Development of the CDK4/6 Inhibitors Ribociclib and Abemaciclib in Breast Cancer. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Abemaciclib, a CDK4 and CDK6 inhibitor for the treatment of metastatic breast cancer. [2021]

3. Australia pubmed.ncbi.nlm.nih.gov

Latest Overview of the Cyclin-Dependent Kinases 4/6 Inhibitors in Breast Cancer: The Past, the Present and the Future. [2020]

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

Cyclin-Dependent Kinase 4/6 Inhibitors for Treatment of Hormone Receptor-Positive, ERBB2-Negative Breast Cancer: A Review. [2023]

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

CDK4/6 Inhibitors Expand the Therapeutic Options in Breast Cancer: Palbociclib, Ribociclib and Abemaciclib. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

An Overview of the Safety Profile and Clinical Impact of CDK4/6 Inhibitors in Breast Cancer-A Systematic Review of Randomized Phase II and III Clinical Trials. [2023]

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

Profile of abemaciclib and its potential in the treatment of breast cancer. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetic drug evaluation of abemaciclib for advanced breast cancer. [2019]

9. Greece pubmed.ncbi.nlm.nih.gov

Abemaciclib-associated Diarrhea: An Exploratory Analysis of Real-life Data. [2023]

10. Japan pubmed.ncbi.nlm.nih.gov

Clinical development of CDK4/6 inhibitor for breast cancer. [2019]

11. Greece pubmed.ncbi.nlm.nih.gov

First clinical experience with CDK4/6 inhibitors in breast cancer therapy. [2021]