Ad/HER2/Neu Dendritic Cell Cancer Vaccine Testing
Condition: Breast Neoplasms; Breast Cancer; Adenocarcinomas; Metastatic Solid Tumors Characterized by HER2/Neu Expression
MeSH terms: Breast Neoplasms
Intervention: Adenoviral Transduced Autologous Human Epidermal Growth Factor Receptor (AdHER)2/neu Dendritic Cell (DC) Vaccine
Intervention description: autologous AdHER2 transduced dendritic cell vaccine manufactured under Good Manufacturing Practices (GMP) conditions from cryopreserved patient monocytes here at the National Institutes of Health (NIH) Clinical Center (CC) Department of Transfusion Medicine (DTM). Vaccine is administered intradermally at assigned dose level at weeks 0, 4, 8, 16 and 24 of the study.
Intervention MeSH terms: Mitogens
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic Solid Tumors; Human Epidermal Growth Factor Receptor 2 Expression (HER2/neu); Trastuzumab Exposure; Dendritic Cell Vaccine; Breast Cancer

Summary:

      Background:

      - Human epidermal growth factor receptor 2 (HER2, also known as c-erbB2 or neu)/neu (HER2) is
      a tumor protein that appears in almost a third of breast cancers and in several other types
      of cancers such as colon, prostate and non-small cell lung. Tumors that overexpress HER2 can
      be associated with a more aggressive cancer, higher recurrence rates, and reduced survival
      rates. Researchers are testing a therapeutic cancer vaccine designed to stimulate the immune
      system to recognize HER2. The vaccine, called adenoviral transduced autologous human
      epidermal growth factor receptor (AdHER)/neu dendritic cell vaccine, is custom-made using an
      individual's own immune cells. These cells will be collected and used to produce the vaccine.

      Objectives:

      - To test the safety and effectiveness of AdHER2 vaccination.

      Eligibility:

      - Individuals at least 18 years of age who have HER2-expressing tumors.

      Design:

        -  Participants will be screened with a physical exam and medical history. Blood and urine
           samples will be collected. Imaging studies will also be performed.

        -  Participants will have an apheresis procedure to collect immune cells to create the
           vaccine.

        -  Participants will receive five doses of the vaccine at study Weeks 0, 4, 8, 16 and 24.

        -  Participants will be monitored with physical exams, frequent blood tests and imaging
           studies.
    

Eligibility criteria:

        -  ELIGIBILITY CRITERIA:

        Common Eligibility for Parts I and II

          -  Adults greater than or equal to 18 with malignant soft tissue and bone tumors and
             recurrent or progressive, metastatic solid tumors who have progressed on standard
             therapies except in adjuvant for high risk bladder cancer in Part I.

          -  Recurrent or progressive disease on prior standard therapies with known clinical
             benefit with the exception of adjuvant bladder cancer population.

          -  Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-1.

          -  Baseline left ventricular ejection fraction (LVEF) by two-dimensional (2D)
             Echocardiogram greater than or equal to 53%.

          -  Greater than or equal to 1 week since standard or investigational treatment for
             metastatic disease.

          -  Stable, concurrent use of hormone therapy for hormone receptor positive breast cancer
             is permitted.

          -  Hematologic parameters: absolute neutrophil count (ANC) greater than or equal to 1000
             cells/mm^3, absolute lymphocyte count (ALC) greater than or equal to 300 cells/mm^3,
             Hemoglobin greater than or equal to 9.0 gm/dL, white blood cell (WBC) greater than or
             equal to 2,500 cells/mm^3, platelet count greater than or equal to 75,000/mm^3,
             prothrombin time (PT)/partial thromboplastin time (PTT) less than or equal to 1.5X the
             upper limits of normal.

          -  Chemistry parameters: Creatinine less than or equal to 1.5 mg/dL, serum
             glutamic-oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase
             (SGPT) less than or equal to 3X the upper limits of normal and total bilirubin less
             than or equal to 1.5 mg/dl, Alkaline phosphatase (Alk PO4) less than or equal to 3X
             the upper limits of normal (except for patients with documented metastatic disease to
             bone and/or liver).

          -  Negative serum beta human chorionic gonadotropin (HCG) if female and of childbearing
             potential.

          -  Negative human immunodeficiency virus (HIV) 1/2 serology and sample drawn for human
             T-cell lymphotropic virus (HTLV). Patients with HIV are excluded from participating on
             this clinical trial because their immunodeficiency would confound the evaluation of
             adverse events which would hinder meeting the primary objective.

          -  Negative serology for hepatitis B and C unless the result is consistent with prior
             vaccination or prior infection with full recovery.

          -  Willingness of female and male subjects to use effective contraception e.g., oral
             contraceptives, barrier device, intrauterine device, or condoms, during the study and
             for three months following the last dose of study vaccine. We suggest that subjects do
             not become pregnant or father a child during the study, and for 3 months following
             receipt of the investigational adenoviral transduced autologous human epidermal growth
             factor receptor (AdHER) dendritic cell (DC) vaccine.

          -  Able to understand and provide Informed Consent.

          -  Patients with 1+ to 3+ human epidermal growth factor receptor 2 (HER2)/neu expression
             by immunohistochemistry (IHC) or an equivocal or positive fluorescence in situ
             hybridization (FISH) result by 2013 American Society of Clinical Oncology
             (ASCO)/Corrective Action Plan (CAP) guideline.

          -  Patients must have measurable disease, per Response Evaluation Criteria in Solid
             Tumors (RECIST) 1.1.

        Part I Eligibility

          -  Naive to trastuzumab (Herceptin), pertuzumab (Perjeta) and lapatinib (Tykerb),
             ado-trastuzumab emtansine (Kadcyla) or other HER2-directed therapies.

          -  Malignancy as follows:

          -  Malignant soft tissue and bone tumors and recurrent or progressive, metastatic solid
             tumors who have progressed on standard therapies; or,

          -  Bladder cancer in the adjuvant setting (adjuvant bladder cancer patients):

               -  Tumor stage T3a, T3b, T4a, T4b and any node positive disease regardless of tumor
                  stage.

               -  Status-post primary cystectomy with curative intent.

               -  May or may not have received neoadjuvant cisplatin-based combination chemotherapy
                  per National Comprehensive Cancer Network (NCCN) guidelines.

               -  May or may not have received adjuvant radiotherapy or chemotherapy based on
                  pathologic risk per NCCN guidelines.

               -  Greater than or equal to 6 weeks s/p primary surgery with curative intent.

          -  NOTE: Patients with breast, ovarian, cervical, colon, gastric/gastroesophageal
             junction, non-small cell lung, renal cell, bladder, malignant soft tissue and bone
             tumor, prostate cancer or other solid tumors.

        Part II Eligibility

          -  Malignant soft tissue and bone tumors and recurrent or progressive, metastatic solid
             tumors who have progressed on standard therapies.

          -  Recurrent or progressive metastatic disease after standard of care HER2-targeted
             therapies, i.e., trastuzumab (Herceptin), pertuzumab (Perjeta), lapatinib (Tykerb),
             ado-trastuzumab emtansine (TDM1) (Kadcyla) or other HER2-directed therapies.

          -  Stable, concurrent use of tamoxifen or aromatase inhibitors for hormone receptor
             positive breast cancer is permitted.

        EXCLUSION CRITERIA:

          -  Pregnant women are excluded from this study because Adenoviral Transduced Autologous
             Human epidermal growth factor receptor (AdHER) dendritic cell (DC) vaccine may have
             the potential for teratogenic or abortifacient effects. Because there is an unknown
             but potential risk for adverse events in nursing infants secondary to treatment of the
             mother with AdHER DC vaccine, breastfeeding should be discontinued if the mother is
             treated with AdHER DC vaccine.

          -  Patients with active central nervous system (CNS) metastases or leptomeningeal
             involvement by tumor (patients with a history of brain metastases who have
             successfully treated for brain metastasis by surgery or radiation and who have not had
             any evidence of the new or progressive CNS disease for more than 12 months are
             eligible).

          -  Patients with rapidly progressing disease in the opinion of the Principal
             Investigator.

          -  Patients with inadequate bilateral peripheral venous or central venous catheter access
             for the required apheresis to allow generation of the autologous AdHER2 DC vaccine
             product.

          -  Clinically significant cardiac dysfunction defined as a history of > New York Heart
             Association (NYHA) Class II symptoms, angina, congestive heart failure, myocardial
             infarction, arrhythmias or cardiac dysfunction requiring treatment or discontinuation
             of chemotherapy.

          -  History of changes in baseline LVEF that occurred during prior treatment with
             anti-HER2 treatment.

          -  Cumulative doxorubicin dose > 400mg/m^2 (>450 mg/m^2 for malignant soft tissue and
             bone tumor patients) or cumulative epirubicin dose > 800mg/m^2.

          -  Use of any standard chemotherapy or other investigational agent(s) within 1 week of
             study enrollment.

          -  Use of systemic corticosteroid therapy within 2 weeks of study enrollment, including
             patients receiving replacement corticosteroid therapy. Note: only topical, inhaled and
             intranasal steroid therapy is permitted.

          -  Active systemic viral, bacterial or fungal infection requiring treatment.

          -  A medical history which the treating physician believes causes the patient to be
             excluded. This includes a remote history of cancer. Please note: Squamous cell
             carcinoma, basal cell carcinoma and remote history of cancer with no evidence of
             recurrence for the past 5 years are eligible.