Abemaciclib in Treating Patients With Surgically Resectable, Chemotherapy Resistant, Triple Negative Breast Cancer
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage IB Breast Cancer AJCC v8
About this trial
This is an interventional treatment trial for Anatomic Stage I Breast Cancer AJCC v8
Eligibility Criteria
Inclusion Criteria:
- Women of age >=18 years
PRE-REGISTRATION: Clinical T1-4, N0-3, M0 breast cancer at diagnosis (prior to the start of neoadjuvant chemotherapy) by American Joint Committee on Cancer (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.
- PRE-REGISTRATION: Histological confirmation of triple negative invasive breast cancer (defined as estrogen receptor [ER] =< 10%, progesterone receptor [PR] =< 10% and HER2 not amplified by in situ hybridization [ISH] or immunohistochemistry [IHC] 0/1) at diagnosis.
PRE-REGISTRATION: Cohort A: Neoadjuvant chemotherapy (NAC) with one of the following regimens that 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)
- Docetaxel in combination with cyclophosphamide (TC) (for patients who are not candidates for anthracyclines)
- Carboplatin or cisplatin in combination with a taxane (paclitaxel, docetaxel, or nab-paclitaxel) (for patients who are not candidates for anthracyclines)
PRE-REGISTRATION: Cohort B: Neoadjuvant chemotherapy (NAC) with one of the following regimens in combination with pembrolizumab that 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)
- Docetaxel in combination with cyclophosphamide (TC)
- Carboplatin or cisplatin in combination with a taxane (paclitaxel, docetaxel, or nab-paclitaxel)
- PRE-REGISTRATION: Residual lesion/enhancement seen in the breast on breast imaging performed after completion of NAC.
- PRE-REGISTRATION: Able to swallow oral medication.
- PRE-REGISTRATION: Willing to undergo biopsy for research.
- PRE-REGISTRATION: Willing to provide tissue and blood samples for correlative research purposes.
- PRE-REGISTRATION: Willing to stop use of strong and moderate inducers and/or strong inhibitors of cytochrome P450 3A =< 7 days prior to registration.
- PRE-REGISTRATION: Provide written informed consent.
- REGISTRATION: Registration must occur =< 56 days after last dose of NAC.
- REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2.
- REGISTRATION: COHORT A GROUP 2 AND COHORT B GROUP 4 ONLY: Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained after completion of NAC but =< 14 days prior to registration).
- REGISTRATION: COHORT A GROUP 2 AND COHORT B GROUP 4 ONLY: Platelets (PLT) >= 100,000/mm^3 (obtained after completion of NAC but =< 14 days prior to registration).
- REGISTRATION: COHORT A GROUP 2 AND COHORT B GROUP 4 ONLY: Hemoglobin (HgB) >= 8.0 g/dL (obtained after completion of NAC but =< 14 days prior to registration).
- REGISTRATION: COHORT A GROUP 2 AND COHORT B GROUP 4 ONLY: Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained after completion of NAC but =< 14 days prior to registration).
- REGISTRATION: COHORT A GROUP 2 AND COHORT B GROUP 4 ONLY: Aspartate transaminase (AST) serum glutamic oxaloacetic transaminase (SGOT) =< 3 x ULN (obtained after completion of NAC but =< 14 days prior to registration).
- REGISTRATION: COHORT A GROUP 2 AND COHORT B GROUP 4 ONLY: Alanine transaminase (ALT) serum glutamate pyruvate transaminase (SGPT) =< 3 x ULN (obtained after completion of NAC but =< 14 days prior to registration).
- REGISTRATION: COHORT A GROUP 2 AND COHORT B GROUP 4 ONLY: Serum creatinine =< 1.5 x ULN (obtained after completion of NAC but =< 14 days prior to registration).
- REGISTRATION: GROUP 2 ONLY: Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only.
Exclusion Criteria:
PRE-REGISTRATION: 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.
- PRE-REGISTRATION: Prior treatment with CDK 4/6 inhibitors (e.g. palbociclib, ribociclib, abemaciclib, etc.)
- PRE-REGISTRATION: Prior treatment with immunotherapy or radiation for this breast cancer.
- PRE-REGISTRATION: Prior incisional or excisional breast biopsy for this cancer.
- PRE-REGISTRATION: Any contraindications to pre-registration biopsy (such as bleeding diatheses, etc.).
- PRE-REGISTRATION: Receiving any investigational agent which would be considered as a treatment for the primary neoplasm.
PRE-REGISTRATION: Other active malignancy =< 3 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.
- PRE-REGISTRATION: Biopsy proven stage IV breast cancer.
- PRE-REGISTRATION: 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 < 30 ml/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).
PRE-REGISTRATION: 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: COHORT A GROUP 2 AND COHORT B GROUP 4: 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.
REGISTRATION: COHORT A GROUP 2 AND COHORT B GROUP 4: Failure to recover to grade 1 or lower from effects of neoadjuvant chemotherapy.
- Exceptions: Residual alopecia and grade 2 peripheral neuropathy are allowed.
- REGISTRATION: COHORT A GROUP 2 AND COHORT B GROUP 4: Concurrent use of strong and moderate inducers and/or strong inhibitors of cytochrome P450 3A =< 7 days prior to registration.
REGISTRATION: COHORT A GROUP 2 AND COHORT B GROUP 4: 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 human immunodeficiency virus [HIV], known active hepatitis B or C).
Sites / Locations
- Mayo Clinic in ArizonaRecruiting
- Mayo Clinic in FloridaRecruiting
- Mayo Clinic in RochesterRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Cohort A Group 1; Cohort B Group 3 (surgery)
Cohort A Group 2; Cohort B Group 4 (abemaciclib, surgery)
Patients undergo standard of care surgical resection.
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.