A Study to Evaluate Abemaciclib for Surgically Resectable, Chemotherapy-Resistant, Triple Negative Breast Cancer

Overview

About this study

The primary purpose of this study is to examine the effects of abemaciclib on the CD8/FOXP3 ratio in chemotherapy-resistant triple negative breast cancer (TNBC) patients following neoadjuvant chemotherapy.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Pre-Registration Inclusion Criteria\:

  • Women of age  ≥ 18 years old.
  • Clinical T1-3, N0-3 breast cancer at diagnosis (prior to the start of 4.1.2neoadjuvant chemotherapy) by AJCC staging version 8.
    Note: Benign breast disease, lobular carcinoma in situ (LCIS) or ductal carcinoma in situ (DCIS) in the contralateral breast is allowed.
    Note: Contralateral invasive breast cancer is allowed if disease is of clinically lower stage and the higher stage lesion will be the study lesion for all biopsies and tissue samples.
  • Histological confirmation of triple negative invasive breast cancer 4.1.3(defined as ER≤10%, PR≤10% and HER2 not amplified by ISH or IHC 0/1) at diagnosis.
  • Neoadjuvant chemotherapy (NAC) with one of the following regimens 4.1.4that was not discontinued early due to intolerability with less than 50% of planned treatment given due to disease progression or patient request:
    • Paclitaxel or docetaxel followed by one of the following: the combination of doxorubicin and cyclophosphamide (AC); the combination of epirubicin and cyclophosphamide (EC) or the combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) Note: Carboplatin may be added to these regimens
    • AC or EC or FEC followed by docetaxel or paclitaxel
      • Note: Carboplatin may be added to these regimens
    • Docetaxel in combination with doxorubicin and cyclophosphamide (TAC)
  • Residual lesion/enhancement seen in the breast on breast imaging performed after completion of NAC.
  • Able to swallow oral medication.
  • Willing to undergo biopsy for research.
  • Willing to provide tissue and blood samples for correlative research purposes.
  • Willing to stop use of strong and moderate inducers and/or strong inhibitors of cytochrome P450 3A ≤ 7 days prior to registration.
  • Provide written informed consent.

Pre-Registration Exclusion Criteria:

  • 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.
    • NOTE: Patients who are on anti-coagulant therapy for maintenance are eligible as long as the DVT and/or PE was > 12 months prior to enrollment and there is no evidence for active thrombosis (either DVT or PE).
      • NOTE: Patients on anticoagulation are eligible; however peri-biopsy and peri-surgical management of anticoagulation is per the institutional standard of care.
  • Prior treatment with CDK 4/6 inhibitors (e.g., palbociclib, ribociclib, abemaciclib, etc.)
  • Prior treatment with immunotherapy or radiation for this breast cancer.
  • Prior incisional or excisional breast biopsy for this cancer.
  • Any contraindications to pre-registration biopsy (such as bleeding diatheses, etc.).
  • Receiving any investigational agent which would be considered as a treatment for the primary neoplasm.
  • Other active malignancy ≤ 5 years prior to registration.
    • EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix.
    • NOTE: If there is a history of prior malignancy, they must not be receiving another specific treatment for prior malignancy.
  • Biopsy proven Stage IV breast cancer.
  • Serious pre-existing medical conditions that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g., estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn’s disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
  • History of any of the following conditions:
    • Syncope of cardiovascular etiology
    • Ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation)
    • Sudden cardiac arrest
      • NOTE: Patients on anticoagulation are eligible; however peri-biopsy and peri-surgical management of anticoagulation is per the institutional standard of care.

Registration Inclusion Criteria:

  • Registration must occur ≤ 56 days after last dose of NAC.
  • ECOG Performance Status (PS) 0, 1, or 2.
  • The following laboratory values obtained after completion of NAC but ≤ 14 days prior to registration:
    • Absolute neutrophil count (ANC) ≥1500/mm3;
    • Platelets (PLT) ≥100,000/mm3;
    • Hemoglobin (HgB) ≥8.0g/dL;
    • Total bilirubin ≤ 1.5 x ULN;
    • Aspartate transaminase (AST)(SGOT) ≤ 3 x ULN;
    • Alanine aminotransferase (ALT)(SGPT) ≤ 3 x ULN;
    • Serum creatinine ≤1.5 x ULN.
  • Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only.

Registration Exclusion Criteria:

  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
    • Pregnant persons;
    • Nursing persons;
    • Persons of childbearing potential who are unwilling to employ adequate contraception.
  • Failure to recover to Grade 1 or lower from effects of neoadjuvant chemotherapy.
    • Exceptions: Residual alopecia and Grade 2 peripheral neuropathy are allowed.
  • Concurrent use of strong and moderate inducers and/or strong inhibitors of cytochrome P450 3A ≤ 7 days prior to registration.
  • Known infections as follows (NOTE: Screening is not required for enrollment):
    • Active systemic  bacterial infection requiring intravenous antibiotics;
    • Active fungal infection (requiring intravenous or oral antifungal treatment);
    • Detectable viral infections (e.g. known HIV, known active hepatitis B or C).

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Alvaro Moreno Aspitia, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Brenda Ernst, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Matthew Goetz, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20462810

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