What side effects are associated with this type of intervention?

Common side effects of Cyclin-Dependent Kinase (CDK) inhibitors like Abemaciclib include neutropenia, diarrhea, fatigue, nausea, and infections. For PARP inhibitors such as Niraparib, typical side effects include anemia, thrombocytopenia, neutropenia, nausea, fatigue, and gastrointestinal symptoms. Both drug classes can cause hematologic toxicities, which are generally manageable with dose adjustments and supportive care.

What prior FDA approvals exist?

Abemaciclib, a Cyclin-Dependent Kinase (CDK) inhibitor, has been approved by the FDA for the treatment of hormone receptor-positive, HER2-negative breast cancer. Other CDK inhibitors approved for similar indications include palbociclib and ribociclib. Niraparib, a PARP inhibitor, is being studied for its efficacy in breast cancer, although other PARP inhibitors like olaparib and talazoparib have already received FDA approval for the treatment of BRCA-mutated, HER2-negative breast cancer. These drugs work by targeting specific pathways involved in cancer cell growth and DNA repair, offering new avenues for treatment.

What other types of research exist?

Promising alternatives to Abemaciclib and Niraparib for breast cancer patients include: 1) Trastuzumab Deruxtecan, an antibody-drug conjugate for HER2-low advanced breast cancer, showing efficacy in previously treated patients. 2) Pembrolizumab, an immune checkpoint inhibitor, particularly for patients with high tumor mutational burden. 3) Olaparib, another PARP inhibitor, which has shown effectiveness in germline BRCA-mutated, HER2-negative metastatic breast cancer. These alternatives offer different mechanisms of action and have shown promising results in recent clinical trials.

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Cyclin-Dependent Kinase Inhibitor

Abemaciclib + Niraparib for Breast Cancer

Phase 1

Waitlist Available

Led By Evie Hobbs, M.D.

Research Sponsored by OHSU Knight Cancer Institute

Eligibility Criteria Checklist

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

Must have

Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

Participants must be planned for neoadjuvant chemotherapy

Must not have

Clinical or radiographic evidence of metastatic disease

Prior history of malignancy within 5 years except for specific cases

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at time of surgical resection (up to 4 months)

Awards & highlights

No Placebo-Only Group

Summary

This trial tests the safety and best dose of two drugs, abemaciclib and niraparib, in patients with a specific type of breast cancer. Abemaciclib blocks proteins needed for cancer cell growth, and niraparib prevents cancer cells from fixing themselves. The goal is to shrink the tumor. Abemaciclib is an orally administered drug approved for treating advanced or metastatic breast cancer.

Who is the study for?

This trial is for individuals with hormone receptor positive, HER2 negative breast cancer who haven't had prior cancer treatment (except endocrine therapy) and are planning surgery. They must have satisfactory lab results, agree to use contraception if applicable, not be pregnant or breastfeeding, and can't have certain heart conditions or a history of other cancers within the last 5 years.

What is being tested?

The trial tests the combination of two drugs before surgery: Abemaciclib which blocks proteins needed for cell growth, and Niraparib which prevents tumor cells from repairing DNA damage. The goal is to see how well these work together to shrink tumors in patients with specific types of breast cancer.

What are the potential side effects?

Potential side effects include issues related to blocking cell growth and DNA repair such as fatigue, nausea, low blood counts leading to increased infection risk or bleeding problems. There may also be liver function changes and risks associated with taking oral medications.

Eligibility Criteria

Inclusion Criteria

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

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I am fully active or can carry out light work.

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I am scheduled for chemotherapy before surgery.

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My cancer is positive for estrogen or progesterone receptors.

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I agree to have a biopsy for research.

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My breast cancer is in an early stage and surgery aims to cure it.

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I have breast cancer in one breast with multiple tumors.

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I haven't had cancer treatment for my breast cancer, except for hormone therapy.

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I can take pills by mouth.

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My cancer is not HER2 amplified according to recent guidelines.

Exclusion Criteria

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

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My cancer has spread to other parts of my body.

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I haven't had any cancer except for certain types in the last 5 years.

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I have received treatments like surgery or chemotherapy for my cancer before joining this study.

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I have been diagnosed with inflammatory breast cancer.

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I have been diagnosed with MDS/AML or show signs of these conditions.

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I cannot have a biopsy or surgery on my breast or lymph nodes due to health risks.

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I have been treated with a PARP or CDK 4/6 inhibitor before.

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I have a history of lung or blood clot issues.

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I have had a surgery to check lymph nodes in my armpit before joining this study.

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I do not have any ongoing serious infections.

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I am not pregnant or breastfeeding.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at time of surgical resection (up to 4 months)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at time of surgical resection (up to 4 months)

This trial's timeline: 3 weeks for screening, Varies for treatment, and at time of surgical resection (up to 4 months) for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Incidence of adverse events (AEs) and serious AEs for the proposed combination

Incidence of dose limiting toxicities (DLTs) for the proposed combination

Secondary study objectives

Clinical benefit rate (CBR)

Heart rate

Rate of delay to breast surgery

+2 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

1Treatment groups

Experimental Treatment

Group I: Treatment (abemaciclib, niraparib)Experimental Treatment2 Interventions

Patients receive abemaciclib PO BID and niraparib PO QD. Treatment repeats every 28 days for up to 2-4 cycles in the absence of disease progression or unacceptable toxicity. Patients who complete 4 cycles undergo standard of care mastectomy or lumpectomy. Patients demonstrating progressive disease after only 2 cycles are switched to receive standard of care chemotherapy prior to undergoing mastectomy or lumpectomy.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Abemaciclib

2019

Completed Phase 2

~1890

0 / 20Eligibility 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

Abemaciclib, a cyclin-dependent kinase (CDK) inhibitor, works by blocking proteins necessary for cell growth, thereby inhibiting the proliferation of tumor cells. Niraparib, a PARP inhibitor, prevents tumor cells from repairing DNA mutations, leading to cell death. These mechanisms are crucial for breast cancer patients, especially those with hormone receptor-positive, HER2-negative breast cancer, as they target specific pathways that drive cancer growth and survival. By disrupting these pathways, these treatments can potentially reduce tumor size and improve patient outcomes.

Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.Hormone Receptor-Positive/Human Epidermal Growth Receptor 2-Negative Metastatic Breast Cancer in Young Women: Emerging Data in the Era of Molecularly Targeted Agents.CDK4/6 inhibitors in breast cancer - from in vitro models to clinical trials.