Abemaciclib + Bicalutamide for Breast Cancer

Recruiting at 2 trial locations

Overseen By Laura A Fiedler, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must be taking: GnRH agonists

Must not be taking: Anti-androgens, Endocrine therapy

Disqualifiers: Brain metastases, Cardiac issues, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the effectiveness and safety of a new combination of two drugs, Abemaciclib and Bicalutamide, for treating a specific type of breast cancer. It focuses on patients with metastatic breast cancer that is HER2-negative and androgen receptor-positive. The trial seeks women with confirmed cases of this breast cancer type who have already received some treatments. Participants should have breast cancer that is recurrent, locally advanced, or metastatic, and they must be able to undergo certain medical assessments, such as scans. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as endocrine therapies like tamoxifen and certain drugs that interact with the study drugs. There is also a required 'washout period' (time without taking certain medications) of at least 21 days for chemotherapy and 14 days for radiotherapy before starting the trial. Please discuss your current medications with the study team to see if any need to be stopped.

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

Research is exploring how the combination of Abemaciclib and Bicalutamide can treat a specific type of breast cancer. The FDA has already approved Abemaciclib for some cancers, indicating a certain level of safety. Studies have shown that most people tolerate it well, though some may experience side effects like diarrhea and tiredness.

Bicalutamide, commonly used for prostate cancer, is generally well-tolerated but can cause hot flashes or fatigue in some patients.

Researchers are testing these two drugs together to assess their effects on androgen receptor-positive, HER2-negative metastatic breast cancer. Early research suggests that most people can manage the combination, but side effects may occur. Those considering joining a trial should discuss potential risks with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Abemaciclib and Bicalutamide for treating androgen receptor-positive, HER2-negative metastatic breast cancer because it offers a fresh angle on targeting cancer cells. Unlike many traditional treatments that primarily focus on hormone receptors like estrogen, this combination includes Bicalutamide, which specifically targets androgen receptors, and Abemaciclib, a CDK4/6 inhibitor that disrupts cancer cell division. This dual approach could potentially enhance effectiveness by attacking the cancer from multiple fronts, offering hope for better outcomes in a treatment-resistant form of breast cancer.

What evidence suggests that this treatment might be an effective treatment for metastatic breast cancer?

This trial will evaluate the combination of two drugs, abemaciclib and bicalutamide, for treating androgen receptor-positive, HER2-negative metastatic breast cancer. Early studies suggest that abemaciclib slows the growth of cancer cells. Bicalutamide, typically used for prostate cancer, blocks certain receptors that some breast cancers require for growth. By combining these drugs, the trial aims to attack the cancer in two different ways, potentially leading to better outcomes. Although researchers are still studying this combination, initial findings are promising for individuals with this type of breast cancer. ^{1 2 4 5 6}

Who Is on the Research Team?

Amy D. Tiersten

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for adults with AR-positive, HER2-negative metastatic breast cancer who've recovered from prior chemotherapy and/or radiotherapy. Participants must have measurable disease, an ECOG status of 0-2, and a life expectancy over 12 weeks. Women must be postmenopausal or on ovarian ablation; men/women must agree to contraception. Exclusions include severe lung impairment, recent major surgery, brain metastases requiring steroids, uncontrolled diabetes or other serious medical conditions.

Inclusion Criteria

My breast cancer is AR+ with at least 1% staining.

My breast cancer is HER2 negative, cannot be surgically removed, and has spread.

I agree to use a condom and not father a child or donate sperm during and for 90 days after the study.

Exclusion Criteria

I haven't taken any cancer treatments in the last 21 days.

I am not pregnant, breastfeeding, and if capable of having children, I am using effective non-hormonal birth control.

I have severe nausea, vomiting, or gut issues that prevent me from taking pills properly.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Abemaciclib in combination with Bicalutamide until disease progression

12 weeks

Continuous daily dosing

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Bicalutamide

Trial Overview The study tests Abemaciclib in combination with Bicalutamide for treating certain metastatic breast cancers. It's an open-label Phase IB/II trial where all participants receive the drugs without placebo control to assess effectiveness and safety.

How Is the Trial Designed?

Group I: Participants with Androgen Receptor-positive, HER2-negative Metastatic Breast Cancer Experimental Treatment 2 Interventions

Abemaciclib in Combination with Bicalutamide

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?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Published Research Related to This Trial

In the MONARCH 3 study involving 493 postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, abemaciclib combined with a nonsteroidal aromatase inhibitor significantly improved progression-free survival (PFS) to 28.18 months compared to 14.76 months for the placebo group.

The objective response rate (ORR) was also higher in the abemaciclib group at 61.0% versus 45.5% in the placebo group, with a tolerable safety profile, although some patients experienced grade ≥3 adverse events like neutropenia and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. Johnston, S., Martin, M., Di Leo, A., et al.[2023]

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, used for treating advanced breast cancer, was generally well tolerated, with the most common adverse event being diarrhea, affecting 42.8% of patients, which was manageable with medications and dose adjustments.

Importantly, dose reductions or early onset of adverse events like diarrhea and neutropenia did not negatively impact progression-free survival, indicating that patients can continue treatment effectively despite these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Abemaciclib-Associated Adverse Events in Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Safety Analysis of MONARCH 2 and MONARCH 3. Rugo, HS., Huober, J., García-Sáenz, JA., et al.[2023]

In a study of 79 Japanese patients with bone metastatic castration-resistant prostate cancer, the combination of radium-223 (Ra-223) and second-generation androgen-receptor targeting agents (ARTAs) showed a trend towards improved overall survival (OS) compared to Ra-223 alone, with median OS of 26.5 months versus 23.5 months, although this difference was not statistically significant.

The combination therapy was well tolerated, with only one patient (4.2%) experiencing a bone fracture, indicating a favorable safety profile, while the extent of disease on bone scans and baseline pain levels were significant predictors of survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognosis and safety of radium-223 with concurrent abiraterone acetate or enzalutamide use for metastatic castration-resistant prostate cancer: Real-world data of Japanese patients. Miyoshi, Y., Yasui, M., Ttsutsumi, S., 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]

RNA sequencing of circulating tumor cells (CTCs) from patients treated with abiraterone or enzalutamide revealed mutations in the androgen receptor and identified the TGFβ and cyclin D1 signaling pathways as key players in resistance to these therapies.

Targeting the downstream effects of SMAD3 and CCND1 may offer new treatment strategies for patients with metastatic castration-resistant prostate cancer who develop resistance to current androgen receptor-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of mechanisms of resistance to treatment with abiraterone acetate or enzalutamide in patients with castration-resistant prostate cancer (CRPC). Pal, SK., Patel, J., He, M., et al.[2021]

New treatments for castration-resistant prostate cancer (CRPC), including enzalutamide, abiraterone, and cabazitaxel, have been approved in Japan, potentially improving patient outcomes.

These approvals, although delayed by 2-3 years compared to Western countries, represent significant advancements in the management of CRPC, with insights provided by experts from both urology and medical oncology fields.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New era of the treatment of CRPC in Japan]. Akaza, H.[2014]

The ERA 223 trial found that combining abiraterone with radium-223 did not improve survival free from symptomatic skeletal events in men with chemotherapy-naïve castration-resistant prostate cancer and bone metastases.

The lack of improvement in outcomes may be linked to bone loss caused by the use of prednisone, which was administered alongside the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher Risk of Fragility Fractures in Prostate Cancer Patients Treated with Combined Radium-223 and Abiraterone: Prednisone May Be the Culprit. Dalla Volta, A., Formenti, AM., Berruti, A.[2022]

Interim results from the MONARCH3 study show that abemaciclib, a CDK4/6 inhibitor, is an effective first-line treatment for advanced ER-positive, HER2-negative breast cancer.

Patients receiving abemaciclib in combination with letrozole experienced significantly improved progression-free survival compared to those receiving a placebo with endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]

The monarchE study focused on patients with high-risk HR+, HER2- early breast cancer, showing that adjuvant treatment with abemaciclib plus endocrine therapy (ET) significantly benefits these patients.

This evidence supports the use of abemaciclib in routine clinical practice for patients identified with high-risk features, potentially improving outcomes for those at risk of cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant Abemaciclib Combined with Endocrine Therapy: Efficacy Results in monarchE Cohort 1. Toi, M., Boyle, F., Im, YH., et al.[2023]

Sipuleucel-T, the first immunotherapy for advanced castration-resistant prostate cancer (CRPC), improved median overall survival by 4.1 months and reduced the risk of death by 22% in asymptomatic patients, showing its efficacy as a treatment option.

Cabazitaxel and abiraterone acetate also demonstrated significant survival benefits, with cabazitaxel improving survival by 2.4 months and reducing death risk by 30%, while abiraterone acetate improved survival by 3.9 months and reduced death risk by 35%, providing new therapeutic options for patients who have progressed after docetaxel therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New agents for the management of castration-resistant prostate cancer. Cersosimo, RJ.[2016]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05095207

Study Details | NCT05095207 | Abemaciclib in ... This is an open label multicenter, Phase IB/II Study of Abemaciclib in Combination with Bicalutamide for Androgen Receptor-positive, HER2-negative ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06365788

Bicalutamide and Abemaciclib in Inoperable or Metastatic ... This study has as goal to evaluate the use of abemaciclib and bicalutamide in androgen receptor positive metastatic triple negative breast cancer. Detailed ...

3. researchgate.net researchgate.net/publication/380313388_Abstract_PO4-19-11_A_Multicenter_Phase_IbII_Study_of_Abemaciclib_in_Combination_with_Bicalutamide_for_Androgen_Receptor-positive_HER2-negative_Metastatic_Breast_Cancer

Abstract PO4-19-11: A Multicenter, Phase Ib/II Study of ... A Multicenter, Phase Ib/II Study of Abemaciclib in Combination with Bicalutamide for Androgen Receptor-positive, HER2-negative Metastatic Breast Cancer [ ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10705204/

Breast Cancer Treatment: To tARget or Not? That Is the Question Clinical trials are currently working on determining the safety and efficacy of combination therapy, including CDK4/6 inhibitors (abemaciclib, ribociclib, and ...

5. clinicaltrials.eu clinicaltrials.eu/trial/study-of-bicalutamide-and-abemaciclib-for-patients-with-advanced-androgen-receptor-positive-triple-negative-breast-cancer/

Study of Bicalutamide and Abemaciclib for Patients with ... This clinical trial investigates the effects of Bicalutamide and Abemaciclib on patients with advanced Androgen Receptor Positive Triple-Negative Breast ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11744844/

Looking beyond the ER, PR, and HER2 Abemaciclib in Combination with Bicalutamide for Androgen Receptor-positive, HER2-negative Metastatic Breast Cancer ... data on androgen receptor ...