Endocrine Therapy + CDK4/6 Inhibitor for Breast Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to identify which patients with metastatic breast cancer respond to a combination of endocrine therapy and a CDK4/6 inhibitor, a type of cancer treatment. Researchers will analyze tumor tissues and blood samples to understand how and why these treatments succeed or fail. The ultimate goal is to tailor breast cancer treatments more effectively. Suitable candidates include men and women with newly diagnosed metastatic breast cancer that is estrogen or progesterone receptor positive and are receiving treatment at Johns Hopkins. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that CDK4/6 inhibitors, like palbociclib, are usually well-tolerated by patients. These drugs can sometimes cause side effects, such as a decrease in white blood cells, which may increase the risk of infection. However, regular check-ups and dose adjustments often manage these side effects.

Almost everyone undergoing hormone therapy experiences some side effects, with hot flashes and joint pain being the most common. Despite these side effects, many patients continue treatment because it can significantly improve survival rates in breast cancer.

Overall, various studies have tested both treatments and shown them to be safe with manageable side effects. Those considering joining a trial should discuss the possible risks and benefits with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of endocrine therapy and CDK4/6 inhibitors for breast cancer because of its unique dual-action approach. Unlike standard treatments that often target hormones alone, this combination not only interferes with hormone-driven cancer growth but also targets the CDK4/6 pathway, which is crucial for cancer cell division. This dual mechanism could potentially improve the effectiveness of treatment, especially in patients with metastatic breast cancer, offering hope for better disease control and longer progression-free survival.

What evidence suggests that this trial's treatments could be effective for metastatic breast cancer?

This trial will evaluate the combination of a CDK4/6 inhibitor with hormone therapy for treating advanced breast cancer. Studies have shown that this combination extends patient survival compared to hormone therapy alone. Research indicates that this treatment is effective for individuals of all ages, regardless of menopausal status, and even if the cancer has metastasized. It appears to improve outcomes for patients who have not yet received treatment for advanced breast cancer. Overall, combining CDK4/6 inhibitors with hormone therapy offers a promising option for managing hormone receptor-positive breast cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Jessica Tao

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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

My breast cancer is advanced or has spread to other parts of my body.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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