Ensayos clínicos

Inclusion Criteria - Pre-Registration :

• 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.

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.
• 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.

Inclusion Criteria - Registration:

• 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/mm^3;
  • Platelets (PLT) ≥100,000/mm^3;
  • 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.

Exclusion Criteria - Registration:

• 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).