What side effects are associated with this type of intervention?

CDK4/6 inhibitors like Abemaciclib, used in treating breast cancer, commonly cause side effects such as diarrhea, neutropenia, fatigue, nausea, and abdominal pain. Chemotherapy, another common treatment, often leads to hair loss, nausea, vomiting, fatigue, and increased risk of infections. Endocrine therapies, such as tamoxifen and aromatase inhibitors, can cause hot flashes, joint pain, and an increased risk of blood clots and bone density loss. Targeted therapies, like HER2 inhibitors, may result in cardiac issues, diarrhea, and skin rashes. Each treatment has a unique side effect profile that should be discussed with a healthcare provider.

What prior FDA approvals exist?

CDK4/6 inhibitors, such as Abemaciclib, Palbociclib, and Ribociclib, have been approved by the FDA for the treatment of hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. These drugs work by inhibiting cyclin-dependent kinases 4 and 6, which are crucial for cell cycle progression. Abemaciclib, in particular, has been approved for use in combination with endocrine therapy or as a monotherapy for patients who have progressed on prior therapies. These treatments have shown efficacy in improving progression-free survival in patients with advanced breast cancer.

What other types of research exist?

Promising novel alternatives to Abemaciclib for breast cancer patients include: 1) Ribociclib and Palbociclib, which are other CDK4/6 inhibitors with proven efficacy. 2) Alpelisib, a PI3K inhibitor, particularly for patients with PIK3CA mutations. 3) Sacituzumab govitecan, an antibody-drug conjugate targeting Trop-2. 4) Pembrolizumab, an immune checkpoint inhibitor, especially for triple-negative breast cancer. 5) Trastuzumab deruxtecan, an antibody-drug conjugate for HER2-positive breast cancer.

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CDK4/6 Inhibitor

Abemaciclib for Triple Negative Breast Cancer

Phase 2

Recruiting

Led By Matthew P Goetz

Research Sponsored by Mayo Clinic

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Residual lesion/enhancement seen in the breast on breast imaging performed after completion of neoadjuvant chemotherapy

Clinical T1-4, N0-3, M0 breast cancer at diagnosis by American Joint Committee on Cancer (AJCC) staging version 8

Must not have

History of deep venous thrombosis (DVT) or pulmonary embolisms (PE) =< 12 months prior to preregistration; OR Active DVT and/or PE requiring anti-coagulant therapy

Receiving any investigational agent which would be considered as a treatment for the primary neoplasm

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 60 days

Awards & highlights

No Placebo-Only Group

Summary

This trial studies how well abemaciclib works in patients with triple negative breast cancer that can be surgically removed but does not respond to chemotherapy. Abemaciclib is a pill that may help stop cancer cell growth by blocking certain enzymes. The trial includes patients who receive different treatments before surgery.

Who is the study for?

This trial is for women aged 18 or older with triple negative breast cancer that remains after chemotherapy and can be surgically removed. Participants must not be pregnant, should have completed chemo within the last 56 days, and cannot use certain drugs affecting liver enzymes. They must also provide tissue samples, swallow pills, and have no other active cancers or serious medical conditions.

What is being tested?

The study tests abemaciclib's effectiveness on patients with resectable triple negative breast cancer resistant to chemotherapy. It examines if this drug can halt cancer cell growth by inhibiting specific enzymes needed for their proliferation. The trial includes surgery as part of the treatment process.

What are the potential side effects?

Abemaciclib may cause side effects such as diarrhea, fatigue, low white blood cell counts (increasing infection risk), nausea, abdominal pain, decreased appetite, vomiting and potential liver enzyme changes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I still have signs of cancer in my breast after chemotherapy.

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My breast cancer is in stages 1-4, may have spread to nearby lymph nodes, but not to distant parts of the body.

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My breast cancer is confirmed to be triple negative.

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I registered for the trial within 56 days after my last chemotherapy before surgery.

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I am willing to have a biopsy for research purposes.

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I am receiving specific chemotherapy before surgery.

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I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had a blood clot in my veins or lungs within the last year or I am currently on blood thinners for a clot.

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I am not currently on any experimental drugs for my cancer.

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I have no medical reasons preventing me from getting a biopsy before joining.

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I have had a breast biopsy for this cancer.

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I have been treated with CDK 4/6 inhibitors before.

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I do not have any known infections.

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I am currently not on chemotherapy, radiotherapy, immunotherapy, or similar treatments.

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My breast cancer is confirmed to be at stage IV.

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I haven't taken strong medication affecting liver enzymes in the last week.

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I still have side effects from earlier chemotherapy that are not mild.

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I have had radiation treatment for my breast cancer.

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I have a history of fainting due to heart issues, irregular heartbeats, or sudden cardiac arrest.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 60 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 60 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 60 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Proportion of patients who have a CD8/FOXP3 ratio < 1.6 in their residual tumors after neoadjuvant chemotherapy (NAC) that convert to CD8/FOXP3 ratio >= 1.6

Secondary study objectives

Changes in vimentin expression

Impact of length of treatment

Incidence of adverse events

Other study objectives

Change in in frequency of JAK-2 amplifications

Change in microbiome with exposure to abemaciclib

Changes in E-Cadherin

+11 more

Side effects data

From 2018 Phase 2 trial • 132 Patients • NCT02102490

91%

Diarrhoea

67%

Nausea

48%

Fatigue

45%

Decreased appetite

35%

Vomiting

27%

Anaemia

26%

Abdominal pain

23%

Asthenia

23%

Neutrophil count decreased

21%

Cough

20%

Constipation

20%

Headache

19%

Arthralgia

18%

White blood cell count decreased

18%

Neutropenia

15%

Alopecia

14%

Dry mouth

14%

Platelet count decreased

14%

Weight decreased

14%

Dysgeusia

13%

Dyspnoea

12%

Abdominal pain upper

12%

Back pain

12%

Dizziness

11%

Oedema peripheral

11%

Dyspepsia

11%

Pyrexia

11%

Blood creatinine increased

10%

Pain

Stomatitis

Aspartate aminotransferase increased

Thrombocytopenia

Lacrimation increased

Dehydration

Dry skin

Pruritus

Alanine aminotransferase increased

Flatulence

Upper respiratory tract infection

Urinary tract infection

Hypokalaemia

Chills

Musculoskeletal chest pain

Musculoskeletal pain

Anxiety

Gastrooesophageal reflux disease

Rash

Myalgia

Cellulitis

Pleural effusion

Atypical pneumonia

Gastroenteritis viral

Lung infection

Sepsis

Fall

Hip fracture

Pneumonitis

Pneumothorax

Febrile neutropenia

Respiratory tract infection

Haematotoxicity

Sinus bradycardia

Tachycardia

Large intestinal obstruction

Pancreatic enzyme abnormality

Pancreatitis

Varices oesophageal

Electrocardiogram abnormal

Liver function test abnormal

Renal function test abnormal

Bone pain

Muscular weakness

Acute kidney injury

Pulmonary embolism

Arterial thrombosis

Epilepsy

100%

80%

60%

40%

20%

Study treatment Arm

Abemaciclib

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Cohort A Group 2; Cohort B Group 4 (abemaciclib, surgery)Experimental Treatment2 Interventions

Patients receive abemaciclib PO BID on days 1-14 or days 1-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgical resection no later than 12 weeks after the last dose of neoadjuvant chemotherapy.

Group II: Cohort A Group 1; Cohort B Group 3 (surgery)Experimental Treatment1 Intervention

Patients undergo standard of care surgical resection.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Abemaciclib

2019

Completed Phase 2

~1890

Therapeutic Conventional Surgery

2005

Completed Phase 3

~9630

0 / 19Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Breast cancer treatments often target specific pathways involved in cancer cell growth and proliferation. CDK4/6 inhibitors, such as Abemaciclib, work by blocking cyclin-dependent kinases 4 and 6, which are crucial for cell cycle progression from the G1 to the S phase, thereby inhibiting cancer cell division. Endocrine therapies, like aromatase inhibitors and selective estrogen receptor modulators, reduce the effects of estrogen on hormone receptor-positive breast cancer cells, slowing their growth. HER2-targeted therapies, such as trastuzumab, bind to the HER2 receptor on cancer cells, preventing them from receiving growth signals. These mechanisms are vital as they offer targeted approaches to halt cancer progression, improve survival rates, and reduce the likelihood of resistance compared to traditional chemotherapy.

The role of abemaciclib in treatment of advanced breast cancer.