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Pathologically confirmed residual invasive breast cancer, in the breast and/or lymph node(s), following neoadjuvant chemotherapy. In the absence of residual invasive disease in the breast, lymph node must contain at least 2mm of invasive disease |
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HER2 negative by local pathology assessed according to current ASCO/CAP guidelines |
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In situ hybridization non-amplified (ratio of HER2 to CEP17 < 2.0 or single probe average HER2 gene copy number < 4 signals/cell), OR |
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Immunohistochemistry (IHC) 0 or IHC 1+ |
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NOTE: If more than one test result is available and not all results meet the inclusion criterion definition, all results should be discussed with the Principal Investigator to establish eligibility |
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ER and PR negative defined as < 1% of cells expressing hormonal receptors via IHC analysis by local laboratory assessment |
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Patients must have received neoadjuvant chemotherapy prior to breast surgery. Investigational agents as part of the neoadjuvant regimen are allowed, with the exception of PI3K/Akt/mTor inhibitors and/or immune checkpoint inhibitors |
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Patients must be within 12 months of last therapy (definitive breast surgery, radiation and/or all intended adjuvant therapy). Definitive breast surgery includes lumpectomy or mastectomy with pathologically clear margins (i.e. no ink on tumor). For patients undergoing lumpectomy, this must be followed by whole breast irradiation. Definitive surgery also includes axillary surgery, either sentinel lymph node biopsy or axillary lymph node dissection at the discretion of the attending surgeon |
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Evidence of circulating tumor cfDNA in blood sample collected after completion of all local and systemic neoadjuvant and adjuvant therapy (preoperative and postoperative chemotherapy, surgery and radiation), confirmed by central testing. Detection of any tumor specific mutations (TSMs) within the sample will be considered positive for purposes of study eligibility |
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Concurrent receipt of bone modifying agents (bisphosphonates or rank-ligand inhibitors)is allowed |
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ECOG Performance Status of 0 or 1 |
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Men and women, age 18 years |
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Adequate hematologic and organ function defined by the following |
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ANC 1.5 109/L (1500/L) without granulocyte colony-stimulating factor support |
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WBC count 2.5 109/L (2500/L) |
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Absolute Lymphocyte count 0.5 109/L (500/L) |
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Platelet count 100 109/L (100,000/L) |
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Hemoglobin 90 g/L (9.0 g/dL), with or without transfusion |
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AST, ALT, and alkaline phosphatase (ALP) 2.5 institutional upper limit of normal (ULN) |
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Serum bilirubin 1.5 institutional ULN with the following exception |
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Patients with known Gilbert syndrome: serum bilirubin level 3 institutional ULN |
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Serum creatinine < 1.5 x institutional ULN |
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Serum albumin 25 g/L (2.5 g/dL) |
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Fasting glucose < 150 mg/dL and hemoglobin (HBA1c) < 7.5% |
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For patients not receiving therapeutic anticoagulation: INR or aPTT 1.5 institutional ULN |
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For patients receiving therapeutic anticoagulation: stable anticoagulant regimen |
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Women of childbearing potential (pre-menopausal) must have a negative serum or urine pregnancy test within 7 days prior to start of therapy. A woman is defined as premenopausal if she is less than 12 months from last menstrual period with no identified cause other than menopause (medication induced amenorrhea is not acceptable). Pregnancy test is not required in women who are surgically sterile via bilateral salpingooophorectomy or hysterectomy |
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Women of childbearing potential and men must agree to use adequate contraception for the duration of protocol treatment and for 28 days after last dose of ipatasertib and 5 months after stopping atezolizumab. Hormonal contraceptives are not acceptable (see section 5.6) |
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Ability to understand and the willingness to sign a written informed consent document |
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Patients must be willing to provide archival tissue for research purposes |
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Clinical evidence of metastatic disease
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Residual DCIS or LCIS alone without invasive cancer OR pT0N0i and pT0N1mic residual disease
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Prior treatment with an immune checkpoint inhibitor is permitted in the neoadjuvant setting and prohibited in the adjuvant setting
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Concurrent enrollment on another investigational therapy trial
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Prior treatment-related toxicity must be resolved to Grade 1 with the exception of alopecia and peripheral neuropathy, prior to study enrollment
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Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
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Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study
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Intercurrent illness including, but not limited to: ongoing or active infection requiring systemic therapy, active tuberculosis, serious liver disease such as cirrhosis, active bleeding diathesis, uncontrolled Type I or Type II diabetes mellitus, Grade 2 uncontrolled or untreated hypercholesterolemia, Hypertriglyceridemia or hypercalcemia
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Cardiovascular disease including: congestive heart failure of New York Heart Association Class III or IV, myocardial infarction (<6 months prior to enrollment) unstable angina pectoris, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease, in the opinion of the investigator
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History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
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Active (acute or chronic) autoimmune disease of any type except hypothyroidism on a thyroid-replacement hormone,or celiac disease, or well-controlled psoriasis, eczema, lichen simplex chronicus or vitiligo
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Impairment of gastrointestinal function or active gastrointestinal disease that may significantly alter the absorption of the study agents (e.g., ulcerative disease, uncontrolled nausea(> grade 2), vomiting (> grade 2), diarrhea (> grade 2), malabsorption syndrome or small bowel resection)
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Congenital long QT syndrome or screening QT interval corrected through use of Fridericia's formula >480 ms
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Participants known to be positive for the human immunodeficiency virus (HIV), Hepatitis B antigen (HepBsAg), or Hepatitis C virus (HCV) RNA are ineligible
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History of prior invasive breast cancer in either breast
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Participants with history of prior malignancy other than breast cancer are eligible if they have been disease-free for at least 5 years prior to enrollment with the exception of patients with thyroid cancer that has been definitively treated without spread to regional lymph nodes
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Treatment with strong CYP3A4 inducers within 4 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug
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Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine while on protocol treatment
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Known allergy or hypersensitivity to any of the study drugs or any of their excipients, including chimeric or humanized antibodies or fusion proteins and Chinese hamster ovary cell products or recombinant human antibodies
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Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study, with the following exceptions
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Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible. o Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study
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Pregnant women are excluded from this study because the effects of ipatasertib and atezolizumab on a developing fetus are unknown. Breastfeeding should be discontinued prior to entry onto the study
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