Clinical Trials /

Safety Study Of Chemotherapy Combined With Dendritic Cell Vaccine to Treat Breast Cancer

NCT02018458

Description:

The primary objective of this study is to determine the safety and feasibility of combining cyclin B1/WT-1/CEF (antigen)-loaded DC vaccination with preoperative chemotherapy. The secondary objectives of this trial are to determine pathologic complete response rates; disease-free survival; to assess immune biomarkers of immunity (antigen-specific CD8+ T cell immunity and TH2 T cells) in breast cancer biopsy specimens and blood samples in patients receiving DC vaccinations; and to assess the feasibility of immunizing LA TNBC and ER+/HER2- BC patients with patient-specific tumor antigens.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Safety Study Of <span class="go-doc-concept go-doc-intervention">Chemotherapy</span> Combined With Dendritic Cell Vaccine to Treat <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: Safety Study Of Chemotherapy Combined With Dendritic Cell Vaccine to Treat Breast Cancer
  • Official Title: Pilot Safety Trial of Preoperative Chemotherapy Combined With Dendritic Cell Vaccine in Patients With Locally Advanced, Triple-Negative Breast Cancer or ER-Positive, Her2-Negative Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02018458

    ORG ID: 013-154

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    The primary objective of this study is to determine the safety and feasibility of combining
    cyclin B1/WT-1/CEF (antigen)-loaded DC vaccination with preoperative chemotherapy.

    The secondary objectives of this trial are to determine pathologic complete response rates;
    disease-free survival; to assess immune biomarkers of immunity (antigen-specific CD8+ T cell
    immunity and TH2 T cells) in breast cancer biopsy specimens and blood samples in patients
    receiving DC vaccinations; and to assess the feasibility of immunizing LA TNBC and ER+/HER2-
    BC patients with patient-specific tumor antigens.

    Detailed Description

    Recent studies have shown that human breast cancers can be immunogenic, and that enhancing
    the immune effector function already present may augment the cytotoxic effects of standard
    therapies.

    vaccination remains the most attractive strategy because of its expected inducement of both
    therapeutic T cell immunity (effector T cells) and protective T cell immunity
    (tumor-specific memory T cells that can control tumor relapse). Several clinical studies
    have now demonstrated that immunity against tumor antigens can be enhanced in cancer
    patients by vaccination with ex vivo-generated tumor antigen-loaded dendritic cells (DCs).
    This strategy capitalizes on the unique capacity of DCs to prime lymphocytes and to regulate
    and maintain immune responses.

    Our goals are to boost T cell immunity targeted against breast cancer utilizing a tumor
    antigen-loaded DC vaccine, to enhance chemotherapy effectiveness and decrease tumor
    metastagenicity, and to decrease the recurrence rates of LA TNBC and ER+/HER2- BC. Patients
    will be treated with a combination of antigen-loaded DC vaccinations along with standard
    preoperative chemotherapy, to improve immunogenicity and to increase the pCR rate achieved
    with standard therapy. The trial will consist of 2 patient cohorts: TNBC and ER+/HER2- BC.

    Trial Arms

    Name Type Description Interventions
    LA TNBC: DC vaccine+Preop chemo Experimental LA TNBC patients will receive standard preop AC followed by TCb chemo for 24 weeks. Chemo and DC vaccinations will be given intratumoral and subcutaneous for 4 times prior surgery. During the AC cycles, vaccines will be given on any day between Days 9-12 of Cycles 1 and 3 of AC. Vaccines will be given on any day between Days 11-15 of Cycles 1 and 3 of TCb. Patients will undergo biopsies of their cancer prior to treatment and 1-2 days prior to or on Day 1 of Cycle 4 of AC. After this, patients will have surgery, locoregional radiation therapy to the breast or chest wall and regional lymphatics per standard of care, and will receive 3 boost DC vaccinations subcutaneously, rotating injection sites in the upper arm. The 1st vaccination will occur after the surgery and prior to radiation; 2nd will occur 30 days 3 days after radiation; the 3rd will occur 90 days 3 days after the 2nd boost.
    ER+/HER2-BC:DC vaccine+Preop chemo Experimental ER+/HER2- BC patients will receive standard preop AC followed by weekly T given for 22 weeks. Chemo and DC vaccinations will be given intratumoral and subcutaneous, for 4 times prior surgery. During the AC cycles, vaccines will be given any day between Days 9-12 of Cycles 1 and 3 of AC. Vaccines will be given on Day 1 during Cycle 2 or Cycle 3 and on Day 1 during either Cycle 8 or Cycle 9 of T. Vaccine will be given after T infusion is completed. Patients will undergo biopsies of their cancer prior to treatment and 1-2 days prior to or on Day 1 of Cycle 4 of AC. Patients will have surgery, locoregional radiation therapy to the breast or chest wall and regional lymphatics per standard of care, and will receive 3 boost DC vaccinations subcutaneously, rotating injection sites in the upper arm. The 1st vaccination will occur after surgery and prior to radiation; the 2nd will occur 30 days 3 days after radiation; and the 3rd will occur 90 days 3 days after the 2nd boost.

    Eligibility Criteria

    - Inclusion Criteria:

    A patient will be considered for enrollment in this study if all of the following criteria
    are met:

    1. Female patients 18 years of age.

    2. Have either:

    1. locally advanced TNBC defined as invasive ductal cancer; ER- tumors with <10% of
    tumor nuclei immunoreactive; PR- tumors with <10% of tumor nuclei
    immunoreactive; T3 or T4 disease, regardless of nodal status (T2 disease is
    eligible if there are positive lymph nodes present by physical exam or imaging
    evaluation or histological evaluation, OR

    2. High-risk ER+ breast cancer defined as grade 3 invasive ductal or mixed
    ductal/lobular cancers, or grade 2 with Ki67 20%; node positive as evidenced by
    physical exam or imaging evaluation or histological evaluation.
    3. HER2- negative breast cancer. If HER2-, it is defined as follows:

    1. FISH-negative (FISH ratio <2.0), or

    2. IHC 0-1+, or

    3. IHC 2+ AND FISH-negative (FISH ratio<2.0)

    4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 5. Adequate
    hematologic function, defined by:

    1. Absolute neutrophil count (ANC) >1500/mm3

    2. Platelet count 100,000/mm3

    3. Hemoglobin >9 g/dL (in the absence of red blood cell transfusion) 6. Adequate liver
    function, defined by:

    a. AST and ALT 2.5 x the upper limit of normal (ULN) b. Total bilirubin 1.5 x ULN 7.
    Adequate renal function, defined by:

    a. Serum creatinine 1.5 x ULN or calculated creatinine clearance of 60 ml/min 8.
    Patients with previous history of invasive cancers (including breast cancer) are eligible
    if definitive treatment was completed more than 5 years prior to initiating current study
    treatment, and there is no evidence of recurrent disease. 9. Eligible for treatment with
    paclitaxel, doxorubicin, cyclophosphamide and carboplatine. 10.Patient must be accessible
    for treatment and follow-up. 11.Patients must be willing to undergo research biopsies to
    obtain breast cancer tissue for whole exome sequencing and evaluation of tumor immune
    microenvironment. 12.All patients must be able to understand the investigational nature of
    the study and give written informed consent prior to study entry.

    - Exclusion Criteria:

    A patient will be ineligible for inclusion in this study any of the following criteria are
    met:

    1. Evidence of metastatic disease on bone scan and CT scan of chest/abdomen (or PET CT
    scan). Patients with intrathoracic metastatic adenopathy are eligible.

    2. Active infection or unexplained fever >38.5C during screening.

    3. Active infections including viral hepatitis and HIV.

    4. Active asthma or other condition requiring steroid therapy.

    5. Autoimmune disease including lupus erythematosus or rheumatoid arthritis. Topical or
    inhaled corticosteroids are allowed.

    6. Patients who are currently receiving or who have received previous systemic therapy
    for breast cancer (eg, chemotherapy, antibody therapy, targeted agents).The use of an
    LHRH agonist during chemotherapy in premenopausal women who wish to preserve ovarian
    function is allowed, but is not required.

    7. Women who are pregnant or lactating. All patients with reproductive potential must
    agree to use effective contraception from time of study entry until at least 3 months
    after the last administration of study drug.

    8. Have a NYHA Class III or IV CHF or LVEF <55%. Patients with significant cardiac
    disease history within 1 year or ventricular arrhythmias requiring medication are
    also excluded.

    9. Patients who have any severe and/or uncontrolled medical conditions or other
    conditions that could affect their participation such as:

    1. severe impaired lung functions as defined as spirometry and DLCO that is 50% of
    the normal predicted value and/or O2 saturation that is 88% or less at rest on
    room air

    2. uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN

    3. liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class
    C).

    10. History of any other disease, physical examination finding, or clinical laboratory
    finding giving reasonable suspicion of a disease or condition that contraindicates
    use of an investigational drug, or that might affect interpretation of the results of
    this study, or render the patient at high risk for treatment complications.

    11. Any other investigational or anti-cancer treatments while participating in this
    study.

    12. Any other cancer

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 80 Years

    Eligible Gender: Female

    Primary Outcome Measures

    Safety of DC vaccine combined with chemotherapy, and DC vaccine combined with chemotherapy

    Secondary Outcome Measures

    Pathologic complete response rate with DC vaccine

    Disease free survival with DC vaccine

    Trial Keywords

    Dendritic cell vaccine

    Breast Cancer

    Doxorubicin

    Paclitaxel

    Cyclophosphamide

    Carboplatin