Carboplatin With or Without Atezolizumab in Treating Patients With Stage IV Triple Negative Breast Cancer
Condition: Triple Negative Breast Cancer; Stage IV Breast Cancer; HER2 Negative; Invasive Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Intervention: Atezolizumab; Carboplatin; Laboratory Biomarker; Quality-of-Life Assessment
Intervention description: Given by vein; Given by vein; Correlative study; Ancillary studies
Intervention MeSH terms: Carboplatin; Atezolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 106.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well carboplatin with or without atezolizumab
      works in treating patients with stage IV triple negative breast cancer. Drugs used in
      chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells,
      either by killing the cells, by stopping them from dividing, or by stopping them from
      spreading. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of
      tumor cells to grow and spread. Giving carboplatin with atezolizumab may work better in
      treating patients with stage IV triple negative breast cancer
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must provide informed written consent

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Clinical stage IV ER, PR, HER2 negative invasive mammary carcinoma, previously
             documented by histological analysis and that meets the following criteria:

          -  HER2 negativity is defined as any of the following by local laboratory assessment:
             In-situ hybridization (ISH) non-amplified (ratio of HER2 to CEP17 < 2.0 or single
             probe average HER2 gene copy number < 4 signals/cell), or IHC 0 or IHC 1+ (if more
             than one test result is available and not all results meet the inclusion criterion
             definition, all results should be discussed with the protocol chair to establish
             eligibility of the patient)

          -  ER and PR negativity are defined as =< 5% of cells expressing hormonal receptors via
             IHC analysis

          -  Willing to undergo biopsy of a metastatic lesion (in patients with reasonably
             accessible metastatic lesions such as chest wall, skin, subcutaneous tissue, lymph
             nodes, bones, peripheral lung, and liver metastases)

          -  Measurable disease, defined as at least one lesion that can be accurately measured in
             at least one dimension by RECIST criteria version (v)1.1

          -  Zero or one prior chemotherapy regimens for metastatic disease

          -  No prior treatment with carboplatin

          -  Absolute neutrophil count (ANC) >= 1500/mm^3 (without granulocyte colony-stimulating
             factor [G-CSF] support within 2 weeks prior to cycle 1, day 1)

          -  Lymphocyte count >= 500/uL

          -  Platelet count >= 100,000/mm^3 (without transfusion within 2 weeks prior to cycle 1,
             day 1)

          -  Hemoglobin >= 9.0 g/dL

             * Patients may be transfused or receive erythropoietic treatment to meet this
             criterion

          -  Calculated creatinine clearance >= 30 mL/min using the Calvert Formula

          -  Bilirubin =< 2.5 x upper limits of normal if no liver metastases present; serum total
             bilirubin must be =< 3 x upper limits of normal for patients with Gilbert disease;
             total bilirubin =< 5 x upper limits of normal if liver metastases present

          -  Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase
             (SGPT) =< 2.5 x upper limits of normal if no liver metastases present; SGOT, SGPT =< 5
             x upper limits of normal if liver metastases present

          -  Alkaline phosphatase =< 2.5 x upper limits of normal if no liver metastases present;
             alkaline phosphatase =< 5 x upper limits of normal if liver metastases present

          -  For patients who are not postmenopausal (women) or surgically sterile (absence of
             ovaries and/or uterus or vasectomy), agreement to remain abstinent or to use two
             adequate methods of contraception (e.g., condoms, diaphragm, vasectomy/vasectomized
             partner, tubal ligation), during the treatment period and for at least 30 days after
             the last dose of study treatment; hormone based oral contraceptives are not allowed on
             study; postmenopausal is defined as:

          -  Age >= 60 years

          -  Age =< 60 years and amenorrheic for 12 months in the absence of chemotherapy,
             tamoxifen, toremifene, or ovarian suppression; or follicle stimulating hormone and
             estradiol in the postmenopausal range

          -  Subjects must complete all baseline screening assessments

        Exclusion Criteria:

          -  CANCER-SPECIFIC EXCLUSION CRITERIA

          -  Spinal cord compression not definitively treated with surgery and/or radiation, or
             previously diagnosed and treated spinal cord compression without evidence that disease
             has been clinically stable for > 2 weeks prior to randomization

          -  Known central nervous system (CNS) disease, except for treated asymptomatic CNS
             metastases, provided all of the following criteria are met: measurable disease outside
             the CNS, only supratentorial metastases allowed (i.e., no metastases to midbrain,
             pons, medulla, or spinal cord), no evidence of progression or hemorrhage after
             completion of CNS-directed therapy, no ongoing requirement for dexamethasone as
             therapy for CNS disease (anticonvulsants at a stable dose are allowed), no
             stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to
             randomization

          -  Leptomeningeal disease

          -  Uncontrolled tumor-related pain: patients requiring narcotic pain medication must be
             on a stable regimen at registration; symptomatic lesions (e.g., bone metastases or
             metastases causing nerve impingement) amenable to palliative radiotherapy should be
             treated prior to randomization; patients should be recovered from the effects of
             radiation; there is no required minimum recovery period; asymptomatic metastatic
             lesions whose further growth would likely cause functional deficits or intractable
             pain (e.g., epidural metastasis that is not presently associated with spinal cord
             compression) should be considered for loco-regional therapy if appropriate prior to
             randomization

          -  Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or
             corrected serum calcium > upper limit of normal [ULN]) or symptomatic hypercalcemia
             requiring continued use of bisphosphonate therapy; patients who are receiving
             denosumab must discontinue denosumab use and replace it with a bisphosphonate instead
             while on study; patients receiving a bisphosphonate for skeletal metastases are not
             excluded and can continue treatment

          -  Malignancies other than triple negative breast cancer (TNBC) within 5 years prior to
             randomization, with the exception of those with a negligible risk of metastasis or
             death and treated with expected curative outcome (such as adequately treated carcinoma
             in situ of the cervix or basal or squamous cell skin cancer)

          -  Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery,
             immunotherapy, hormonal therapy, biological therapy) other than the ones specified in
             the protocol; any other investigational drugs should be discontinued 2 weeks prior to
             the first dose of study medication

          -  GENERAL MEDICAL EXCLUSION CRITERIA

          -  Women only: pregnancy or lactation

          -  Evidence of significant uncontrolled concomitant disease that in the opinion of the
             investigator could affect compliance with the protocol or interpretation of results,
             including significant liver disease (such as cirrhosis, uncontrolled major seizure
             disorder, or superior vena cava syndrome)

          -  Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac
             disease (class II or greater), myocardial infarction within 3 months prior to
             randomization, unstable arrhythmias, or unstable angina; patients with a known left
             ventricular ejection fraction (LVEF) < 40% will be excluded; patients with known
             coronary artery disease, congestive heart failure not meeting the above criteria, or
             LVEF < 50% must be on a stable medical regimen that is optimized in the opinion of the
             treating physician, in consultation with a cardiologist if appropriate

          -  Severe infection requiring systemic treatment within 4 weeks prior to randomization,
             including but not limited to hospitalization for complications of infection,
             bacteremia, or severe pneumonia

          -  Major surgical procedure within 4 weeks prior to randomization or anticipation of the
             need for a major surgical procedure during the course of the study other than for
             diagnosis; placement of central venous access catheter(s) (e.g., port or similar) is
             not considered a major surgical procedure and is therefore permitted

          -  History of severe reactions (e.g. allergic, anaphylactic, or other hypersensitivity)
             to chimeric or humanized antibodies or fusion proteins

          -  Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster
             ovary cells or any component of the atezolizumab formulation

          -  History of autoimmune disease, including but not limited to myasthenia gravis,
             myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
             inflammatory bowel disease, vascular thrombosis associated with antiphospholipid
             syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome,
             multiple sclerosis, vasculitis, or glomerulonephritis; patients with a history of
             autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are
             eligible for this study; patients with controlled type 1 diabetes mellitus on a stable
             insulin regimen are eligible for this study

          -  Prior allogeneic stem cell or solid organ transplantation

          -  History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
             pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic
             organizing pneumonia), or evidence of active pneumonitis on screening chest computed
             tomography (CT) scan; history of radiation pneumonitis in the radiation field
             (fibrosis) is permitted

          -  Positive test for human immunodeficiency virus (HIV) (testing required prior to
             registration)

          -  Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg]
             test at screening) or hepatitis C

          -  Patients with past hepatitis B virus (HBV) infection or resolved HBV infection
             (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive
             antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible

          -  Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase
             chain reaction (PCR) is negative for HCV RNA

          -  Active tuberculosis

          -  Receipt of a live, attenuated vaccine within 4 weeks prior to initiation of study drug
             (cycle 1, day 1 [C1D1]) or anticipation that such a live, attenuated vaccine will be
             required during the study

          -  Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or
             pathway-targeting agents

          -  Treatment with systemic immunostimulatory agents (including but not limited to
             interferons or IL-2) within 4 weeks or five half-lives of the drug (whichever is
             shorter) prior to randomization

          -  Treatment with systemic corticosteroids or other systemic immunosuppressant
             medications (including but not limited to prednisone, dexamethasone, cyclophosphamide,
             azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents)
             within 2 weeks prior to cycle 1, day 1, or anticipated requirement for systemic
             immunosuppressive medications during the trial; patients who have received acute,
             low-dose, systemic immunosuppressant medications (e.g., a one-time dose of
             dexamethasone for nausea) may be enrolled in the study; patients with a history of
             allergic reaction to IV contrast requiring steroid pre-treatment should have baseline
             and subsequent tumor assessments performed using magnetic resonance imaging (MRI); the
             use of inhaled corticosteroids for chronic obstructive pulmonary disease,
             mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension,
             and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed

          -  Psychiatric illness/social situations that would compromise patient safety or limit
             compliance with study requirements