Clinical Trials /

Nab-Paclitaxel and Atezolizumab Before Surgery in Treating Patients With Triple Negative Breast Cancer

NCT02530489

Description:

This phase II trial studies how well nab-paclitaxel and atezolizumab before surgery work in treating patients with triple negative breast cancer (breast cancer cells that do not have estrogen receptors, progesterone receptors, or large amounts of human epidermal growth factor receptor 2 protein). Drugs used in chemotherapy, such as nab-paclitaxel, 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. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving nab-paclitaxel and atezolizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. This drug combination before surgery may be an effective treatment for triple negative breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Neoadjuvant Trial of <span class="go-doc-concept go-doc-intervention">Nab-Paclitaxel</span> and <span class="go-doc-concept go-doc-intervention">MPDL3280A</span>

Title

  • Brief Title: Neoadjuvant Trial of Nab-Paclitaxel and MPDL3280A
  • Official Title: Triple-Negative First-Line Study: Neoadjuvant Trial of Nab-Paclitaxel and MPDL3280A, a Pdl-1 Inhibitor in Patients With Triple Negative Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02530489

    ORG ID: 2014-1043

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    MPDL3280A MPDL3280A + Nab-paclitaxel
    Nab-paclitaxel Paclitaxel, Abraxane, ABI-007 MPDL3280A + Nab-paclitaxel

    Trial Purpose

    The goal of this clinical research study is to learn if receiving MPDL3280A and abraxane
    (nab-paclitaxel) in combination before surgery and MPDL3280A alone after surgery can help to
    control breast cancer. The safety of this study drug combination will also be studied.

    Detailed Description

    Study Drug Administration:

    Each study cycle is 21 days. You will receive the study drugs in 2 sets of 4 cycles (4
    cycles before surgery and 4 cycles after surgery).

    You will receive MPDL3280A by vein over about 30 minutes on Day 1 of each cycle before and
    after surgery.

    You will receive nab-paclitaxel by vein over about 30 minutes on Day 1 of Cycles 1-4 before
    surgery.

    If you have side effects, the study doctor may decide to lower your dose of study drugs or
    have you stop taking the drugs. You may be able to restart the study drug later at the same
    or a lower dose. The study doctor will discuss this with you.

    Study Visits:

    On Day 1 of all cycles:

    - You will have a physical exam.

    - Blood (about 2 tablespoons) will be drawn for routine tests.

    - During Cycle 3, you will have an ultrasound of your breast(s) before surgery.

    - During Cycle 3, blood (about 1 tablespoon each time) will be drawn before surgery and
    at the time of surgery.

    Within 6 weeks after you have received 4 cycles of study drugs, you will have surgery as
    part of your standard of care and part of the tumor tissue that is removed during surgery
    will be collected for biomarker testing. You will be given a surgery consent form that
    describes the procedure and its risks.

    On Day 21 of Cycle 8, blood (about 1 tablespoon) will be drawn for biomarker testing.

    Length of Treatment:

    You may receive the study drugs for about 4 cycles before your surgery and about 4 cycles
    after your surgery (8 cycles total). You will no longer be able to take the study drug, if
    intolerable side effects occur, or if you are unable to follow study directions. You may be
    able to continue taking the study drugs if the disease gets worse if the doctor thinks it is
    in your best interest.

    Your participation on the study will be over after follow-up.

    Follow-Up:

    Every 6 months for up to 3 years, you will either have a clinic visit or you will be called
    by a member of the study staff and asked how you are doing. If you are called, each call
    should last about 15-20 minutes.

    This is an investigational study. MPDL3280A is not FDA approved or commercially available.
    It is currently being used for research purposes only. Nab-paclitaxel is FDA approved and
    commercially available for the treatment of metastatic (has spread) breast cancer. The
    study doctor can explain how the study drug combination is designed to work.

    Up to 37 participants will be enrolled in this study. All will take part at MD Anderson.

    Trial Arms

    Name Type Description Interventions
    MPDL3280A + Nab-paclitaxel Experimental MPDL3280A administered at 1200 mg by vein every 3 weeks for 12 weeks in the neoadjuvant setting in combination with Nab-paclitaxel 100 mg/m2 by vein weekly for 12 weeks. Within 4 weeks after surgery, participants start another 4 cycles of MPDL3280A in the adjuvant setting to complete a total of 8 cycles of treatment with MPDL3280A. MPDL3280A, Nab-paclitaxel

    Eligibility Criteria

    Inclusion Criteria:

    1. Signed written informed consent

    2. Histologically confirmed primary invasive adenocarcinoma of the breast with the size
    of the primary tumor being at least 1.5 cm on imaging by either mammography,
    ultrasound or breast MRI

    3. ER and PR expression both <10% by immunohistochemistry (IHC) and HER2 0 or 1+ by IHC
    or non-amplified HER2 expression as determined by Fluorescence In Situ Hybridization
    (FISH)

    4. No prior treatment for primary invasive adenocarcinoma of the breast such as
    irradiation, chemotherapy, hormonal therapy, immunotherapy, investigational therapy
    or surgery other than the anthracycline and cyclophosphamide chemotherapy with or
    without 5-fluorouracil given as part of participation in protocol 2014-0185.
    Treatment for ductal carcinoma in situ is allowed, such as surgery, hormonal therapy
    and radiotherapy

    5. ECOG performance status of 0-1

    6. Baseline MUGA or echocardiogram scans with LVEF of > 50%

    7. Patient must have adequate organ function as determined by the following laboratory
    values: ANC >/= 1500 cells/uL, WBC counts > 2500/uL, Lymphocyte count >/= 300/uL,
    Platelet count >/=100,000/uL; Hemoglobin >/= 9.0 g/dL, Total bilirubin </= 1.5 x
    upper limit of normal (ULN) with the following exception: Patients with known Gilbert
    disease who have serum bilirubin level </= 3 x ULN may be enrolled. AST and ALT </=
    3.0 x ULN with the following exception: Patients with liver involvement: AST and/or
    ALT </= 5 x ULN, Alkaline phosphatase </= 2.5 x ULN with the following exception:
    Patients with documented liver involvement or bone metastases: alkaline phosphatase
    </= 5 x ULN

    8. Serum creatinine </= 1.5 x ULN or creatinine clearance >/= 50 mL/min on the basis of
    the Cockcroft-Gault glomerular filtration rate estimation: (140 - age) x (weight in
    kg) x (0.85 if female)/ 72 x (serum creatinine in mg/dL), INR and aPTT </= 1.5 x ULN.
    This applies only to patients who do not receive therapeutic anticoagulation;
    patients receiving therapeutic anticoagulation (such as low-molecular-weight heparin
    or warfarin) should be on a stable dose

    9. Men or women 18 years of age or older

    10. Women of childbearing potential must be using an adequate method of contraception to
    avoid pregnancy throughout the study and for up to 8 weeks after the last dose of
    investigational product in such a manner that the risk of pregnancy is minimized. Men
    on study also must be using contraception. Women of childbearing potential (WOCBP)
    are women who have not been postmenopausal greater than 1 year or undergone a
    hysterectomy or bilateral oophorectomy

    11. Negative serum or urine pregnancy test for women within 72 hours of receiving the
    first dose of the study medication for women of childbearing potential

    12. Participated on protocol 2014-0185 TNBC Neoadjuvant Triaging protocol and classified
    as a "chemotherapy-insensitive" after anthracycline-based chemotherapy either by
    insufficient tumor shrinkage (<80%) by diagnostic imaging or classified as a
    non-responder by the molecular predictor as part of their participation in protocol
    2014-0185

    Exclusion Criteria:

    1. Women who are pregnant or breast-feeding

    2. Known metastatic disease

    3. Disease free of prior malignancy for < 5 years with the exception of curatively
    treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, or
    transitional cell carcinoma.

    4. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
    anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
    ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
    or checkpoint pathways)

    5. Has had major surgery within 21 days before Cycle 1, Day 1

    6. Uncontrolled inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)

    7. Myocardial infarction within 6 months before starting therapy, symptomatic congestive
    heart failure (New York Heart Association > class II), unstable angina, or unstable
    cardiac arrhythmia requiring medication

    8. Serious intercurrent infections or non-malignant medical illness that are
    uncontrolled or the control of which may be jeopardized by this therapy

    9. Psychiatric disorders or other conditions rendering the subject incapable of
    complying with the requirements of the protocols

    10. History or risk of autoimmune disease, including but not limited to systemic lupus
    erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
    associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjgren's
    syndrome, Bell's palsy, Guillain-Barr syndrome, multiple sclerosis, autoimmune
    thyroid disease, vasculitis, or glomerulonephritis. Patients with a history of
    autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be
    eligible. Patients with controlled Type 1 diabetes mellitus on a stable insulin
    regimen may be eligible.

    11. Continued from #9: Patients with eczema, psoriasis, lichen simplex chronicum of
    vitiligo with dermatologic manifestations only (e.g., patients with psoriatic
    arthritis would be excluded) are permitted provided that they meet the following
    conditions: Patients with psoriasis must have a baseline ophthalmologic exam to rule
    out ocular manifestations Rash must cover less than 10% of body surface area (BSA)
    Disease is well controlled at baseline and only requiring low potency topical
    steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone
    0.01%, desonide 0.05%, alclometasone dipropionate 0.05%) No acute exacerbations of
    underlying condition within the last 12 months (not requiring psoralen plus
    ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral
    calcineurin inhibitors; high potency or oral steroids)

    12. Known to be human immunodeficiency virus positive

    13. Patients with prior allogeneic stem cell or solid organ transplantation

    14. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
    pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterates, cryptogenic
    organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan.
    History of radiation pneumonitis in the radiation field (fibrosis) is permitted

    15. Patients with 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 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 is negative for HCV RNA

    16. Active tuberculosis

    17. Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or
    anticipation that such a live, attenuated vaccine will be required during the study.
    Influenza vaccination should be given during influenza season only (approximately
    October to March). Patients must not receive live, attenuated influenza vaccine
    (e.g., FluMist) within 4 weeks prior to Cycle 1, Day 1 or at any time during the
    study

    18. 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

    19. Treatment with systemic corticosteroids or other systemic immunosuppressive
    medications (including but not limited to prednisone, dexamethasone,
    cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis
    factor [TNF] agents), or anticipated requirement for systemic immunosuppressive
    medications during the trial. Patients who have received acute, low dose, systemic
    immunosuppressant medications (e.g., dexamethasone prior to the anthracycline-based
    chemotherapy for nausea) may be enrolled in the study. The use of inhaled
    corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed

    20. Concurrent disease or condition that would interfere with study participation or
    safety, such as any of the following: Active, clinically significant infection either
    grade > 2 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse
    Events (CTCAE) v4.03 or requiring the use of parenteral anti-microbial agents within
    14 days before Day 1 of study drug, Clinically significant bleeding diathesis or
    coagulopathy, including known platelet function disorders, Non-healing wound, ulcer,
    or bone fracture

    21. Known hypersensitivity to any of the components of MPDL3280A or nab-paclitaxel

    22. History of severe allergic, anaphylactic, or other hypersensitivity reactions to
    chimeric or humanized antibodies or fusion proteins

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Pathologic Complete Response (pCR) of MPDL3280A in Combination with Nab-paclitaxel

    Secondary Outcome Measures

    Progression Free Survival (PFS)

    Trial Keywords

    Breast Cancer

    Triple negative breast cancer

    TNBC

    Invasive adenocarcinoma of the breast

    MPDL3280A

    Nab-paclitaxel

    Paclitaxel

    Abraxane

    ABI-007