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Clinical Trials Search at Vanderbilt-Ingram Cancer Center

Trastuzumab, Vinorelbine Tartrate, and Avelumab with or without Utomilumab in Treating Patients with HER2-Positive Metastatic Breast Cancer

This phase II trial studies the how well trastuzumab, vinorelbine tartrate, and avelumab with or without utomilumab work in treating patients with HER2-positive breast cancer that has spread to other parts of the body (metastatic). Trastuzumab is a form of targeted therapy because it attaches itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. Immunotherapy with monoclonal antibodies, such as avelumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as vinorelbine tartrate, 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. Utolimumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Giving trastuzumab, vinorelbine tartrate, and avelumab with or without utomilumab may work better in treating patients with breast cancer.
Phase II
Chemotherapy - cytotoxic, Mol. targeted/Immunotherapy/Biologics
Avelumab, Trastuzumab (Herceptin), Utomilumab, Vinorelbine
Abramson, Vandana
Vanderbilt University


18 Years
Inclusion Criteria:

Histologically confirmed breast cancer that is metastatic or unresectable loco-regionally advanced.

Histologically confirmed HER-2 positive breast cancer by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) 2013 guidelines. NOTE: Central confirmation of HER-2 status is not required: * IHC 3+ based on circumferential membrane staining that is complete, intense -AND/OR- * Fluorescence in situ hybridization (FISH) positive based on one of the three following criteria: ** Single-probe average HER2 copy number >= 6.0 signals/cell; OR ** Dual-probe HER2/CEP17 ratio >= 2.0 OR ** Dual-probe HER2/CEP17 ratio = 6.0 signals/cell.

Measurable disease per RECIST version (v)1.1.

Participants must have previous treatment with ado-trastuzumab emtansine (Kadcyla, T-DM1) in any setting.

Participants must have previously received trastuzumab and pertuzumab in the metastatic setting or recurred =
Participants must have progressed on their most recent line of therapy. Progression must have been demonstrated by radiological or clinical assessment.

Left ventricular ejection fraction (LVEF) >= 50%, as determined by multigated acquisition (MUGA) or echocardiogram.

Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

Absolute neutrophil count >= 1250/uL.

Platelet count >= 100,000/uL.

Hemoglobin >= 9 g/dL.

Serum total bilirubin =
Aspartate aminotransferase (AST) =
Alanine aminotransferase (ALT) =
Creatinine == 60 mL/min/1.73 m^2.

Urinary protein: creatinine (UPC) ratio
International normalized ratio (INR) or prothrombin time (PT) =
Willingness and availability to submit formalin-fixed paraffin-embedded (FFPE) tissue for research purposes. This can be from archival tissue from unresectable loco-regional or metastatic disease obtained =
If female of childbearing potential, must have a negative pregnancy test within 7 days of registration. Childbearing potential is defined as: those who have not been surgically sterilized and/or have had a menstrual period in the past 12 months or who have been on ovarian suppression in the past year.

Participants of childbearing potential (males and females as defined above) must be willing to use effective contraception during treatment and up to 7 months after stop of trial treatment. Acceptable methods of contraception are intrauterine devices, bilateral tubal occlusion, vasectomized, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not allowed.

Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Prior therapy with vinorelbine in any setting

Prior therapy with any anti-PD-1, anti-PD-L1, L2, anti-4-1BB (CD137), or anti-CTLA 4 therapy.

Known human immunodeficiency virus (HIV) positive (testing not required).

Active or chronic hepatitis B or C (testing not required)

History of interstitial lung disease.

Active central nervous system metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth (patients with history of central nervous system [CNS] metastases or spinal cord compression are eligible if they are clinically stable for at least 4 weeks before first dose of investigational product and do not require high-dose steroid treatment).

History of clinically significant or uncontrolled cardiac disease, including congestive heart failure (New York Heart Association functional classification > 3), angina, myocardial infarction or ventricular arrhythmia.

Previous severe hypersensitivity reaction to treatment with another monoclonal antibody.

Active infection requiring systemic therapy.

Chronic systemic therapy with immunosuppressive agents including corticosteroids.

Active autoimmune disease or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the trial. Patients with hypothyroidism stable on hormone replacement or Sjogren’s syndrome will not be excluded from the trial.

Concurrent disease or condition that would make the patient inappropriate for trial participation or any serious medical disorder that would interfere with the patient’s safety in the opinion of the treating investigator.

No current uncontrolled hypertension (>= 180/110), unstable diabetes mellitus, dyspnea at rest, or chronic therapy with oxygen.

Chemotherapy, radiotherapy, and/or biological cancer therapy within 3 weeks prior to the planned treatment start date.

Unresolved or unstable adverse events from prior therapy, except alopecia (has not recovered to CTCAE v.4 =
Pregnant women or women who are lactating/breastfeeding due to the teratogenic potential of the study drugs.

Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A are ineligible. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.

Live vaccines within 30 days prior to the first dose of trial therapy and during trial treatment.

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