| Eligibility |
Inclusion Criteria:
- Ability to understand and the willingness to sign a written informed consent document.
- Females (regardless of menopausal status), or males
- Biopsy proven estrogen receptor (ER) and/or progesterone receptor (PR) positive as
defined as ER >= 1% and/or PR >= 1% by immunohistochemistry according to American
Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
for hormone receptor testing
- HER2 non-amplified per 2018 ASCO/CAP guidelines, defined as:
- Immunohistochemistry (IHC) score 0/1+, or
- IHC 2+ and in situ hybridization (ISH) non-amplified with a ratio of HER2 to
CEP17 < 2.0, and if reported, average HER2 gene copy number < 4 signals/cells; or
- ISH non-amplified with a ratio of HER2 to CEP17 < 2.0, and if reported, average
HER2 gene copy number < 4 signals/cells
- Clinical T1-T3, any N, M0 invasive breast cancer, by American Joint Committee on
Cancer (AJCC) 8th edition clinical staging with the goal being curative intent surgery
to completely excise involved tumor in the breast and the draining lymph nodes
- Individuals with unilateral, multi-focal breast cancer (defined as more than one
lesion of invasive breast cancer in the same breast separated from the dominant breast
lesion by less than 5 cm of radiologically normal breast tissue) are eligible
- Participants must be planned for neoadjuvant chemotherapy
- Except for allowable endocrine therapy up to 4 weeks prior to study enrollment,
participants must not have received prior anti-cancer therapy for the treatment of
their breast cancer
- Participant must have disease that is amenable to biopsy, and agree to provide the
required research biopsies at baseline, and 2 months after initiating study therapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- The participant is able to swallow oral medications
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelets >= 100 x 10^9/L
- Hemoglobin >= 9 g/dL
- Total bilirubin =< 1.5 x upper limit of normal (ULN). Participants with Gilbert's
syndrome with a total bilirubin =< 2.0 times ULN and direct bilirubin within normal
limits are permitted
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN
- If a participant is a cancer survivor, they have undergone potentially curative
therapy for all prior malignancies, with no evidence of recurrence > 5 years
- Female participants of childbearing potential (FOCBP) must have a negative serum or
high sensitive urine pregnancy test (per institutional standards) within 7 days prior
to the start of study drugs
- FOCBP must agree to use highly-effective method(s) of contraception during the study
and for 6 months after the last dose of study drugs
- FOCBP are those who have not been surgically sterilized or have not been free from
menses for > 1 year without an alternative medical cause
- Male participants must agree to use an adequate method of contraception starting with
the first dose of study therapy through at least 3 months after the last dose of study
drugs
- Participant must agree to not donate blood during the study or for 90 days after the
last dose of study treatment
- Participants receiving corticosteroids may continue as long as their dose is stable
for least 4 weeks prior to initiating protocol therapy
- Participant must agree to not breastfeed during the study or for 30 days after the
last dose of study treatment
- The participant must have normal BP or adequately treated and controlled hypertension
(systolic BP <=140 mmHg and diastolic BP =90 mmHg).
Exclusion Criteria:
- Prior history of malignancy within 5 years except for successfully treated cervical
carcinoma in situ, lobular carcinoma in situ of the breast, or non-melanoma skin
cancer
- Inflammatory breast cancer defined as clinically significant erythema of the breast
and/or documented dermal lymphatic invasion (not direct skin invasion by tumor or peau
d'orange without erythema) is not eligible
- Participants that have undergone surgical axillary staging procedure prior to study
entry
- Fine needle aspiration (FNA) or core needle biopsy of axillary node is permitted
- Bilateral breast cancer, except for those tumors exhibiting similar biomarkers (grade,
ER/PR, HER2)
- Clinical or radiographic evidence of metastatic disease
- Isolated ipsilateral supraclavicular node involvement is permitted
- A prior history of ductal breast carcinoma in situ (DCIS) treated with
contralateral mastectomy and not receiving endocrine therapy is eligible
- Breast implants are contraindicated only if the implant precludes the required
research biopsies or interferes with palpating the breast lesion
- Prior treatment for this cancer including surgery, radiation therapy, chemotherapy,
biotherapy, hormonal therapy or investigational agent prior to study entry
- Participants may have received up to 4 weeks of endocrine therapy prior to
enrollment on trial
- Participants with myelodysplastic syndrome/acute myeloid leukemia or with features
suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
- Contraindication to undergoing breast and/or axillary lymph node biopsy
- Contraindication to undergoing surgical resection
- Prior therapy with a PARP inhibitor
- Prior therapy with a CDK 4/6 inhibitor
- The patient has active systemic bacterial infection (requiring intravenous [IV]
antibiotics at time of initiating study treatment), fungal infection, or detectable
viral infection (such as known human immunodeficiency virus positivity or with known
active hepatitis B or C [e.g., hepatitis B surface antigen positive]. Screening is not
required for enrollment
- The patient has serious and/or uncontrolled preexisting medical condition(s) that, in
the judgment of the investigator, 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)
- Known history of pneumonitis or interstitial lung disease (ILD)
- Known history of deep vein thrombosis (DVT) or pulmonary embolism (PE)
- Participant must not have received a transfusion (platelets or red blood cells) =< 4
weeks prior to initiating protocol therapy. Exceptions may be made at the discretion
of the investigator for the treatment of clinical complications such as bleeding. In
these cases, protocol therapy may start >= 7 days after transfusion
- Participant must not have received colony stimulating factors (e.g., granulocyte
colony-stimulating factor, granulocyte macrophage colony stimulating factor, or
recombinant erythropoietin) within 4 weeks prior to initiating protocol therapy
- The patient has a personal 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), or sudden
cardiac arrest
- Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible
cardiac conditions, as judged by the investigator (e.g., unstable ischemia,
uncontrolled symptomatic arrhythmia, congestive heart failure, Fridericia's Correction
Formula (QTcF) prolongation > 500 ms, electrolyte disturbances, etc.), or participants
with congenital long QT syndrome
- Uncontrolled hypertension, or hypertension that cannot otherwise be clinically managed
before initiating study therapy
- Psychiatric illness/social situations, or any condition that, in the opinion of the
investigator, would: interfere with evaluation of study treatment or interpretation of
participant safety or study results, or substantially increase risk of incurring
adverse events (AEs), or compromise the ability of the patient to give written
informed consent
- Participant must not have had major surgery =< 3 weeks prior to initiating protocol
therapy and participant must have recovered from any surgical effects
- Hypersensitivity to any study agent, or its excipients, when administered alone
- Females who are pregnant or lactating
- Judgment by the investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions and requirements
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