Clinical Trials /

Type I-Polarized Autologous Dendritic Cell Vaccine With Tumor Blood Vessel Antigen-Derived Peptides in Metastatic Breast Cancer Patients

NCT02479230

Description:

This pilot clinical trial studies the safety of a dendritic cell vaccine when given with gemcitabine hydrochloride in treating patients with breast cancer that has spread beyond the breast and local lymph nodes to other organs in the body. The vaccine is made up of natural cells found in the blood, called dendritic cells, and peptides, or small fragments of protein which are loaded onto the dendritic cells. This combination may help activate the immune system against stromal cells, which are cells that help cancer cells survive in the body. Gemcitabine hydrochloride is a chemotherapy drug that is given before the vaccine to help shrink the tumor and control cells that may interfere with the activity of the vaccine. Interfering with the stromal cells that help support the growth of cancer cells may lead to the death of the cancer cells.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Pilot Trial of a Type I-Polarized Autologous Dendritic Cell Vaccine Incorporating Tumor Blood Vessel Antigen-Derived Peptides in Patients With <span class="go-doc-concept go-doc-disease">Metastatic Breast Cancer</span>

Title

  • Brief Title: Pilot Trial of a Type I-Polarized Autologous Dendritic Cell Vaccine Incorporating Tumor Blood Vessel Antigen-Derived Peptides in Patients With Metastatic Breast Cancer
  • Official Title: Pilot Trial of a Type I-Polarized Autologous Dendritic Cell Vaccine Incorporating Tumor Blood Vessel Antigen-Derived Peptides in Patients With Metastatic Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02479230

    ORG ID: CASE3113

    NCI ID: NCI-2014-00265

    Trial Conditions

    Breast Cancer

    Metastatic Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    gemcitabine hydrochloride 1-(2-oxo-4-amino-1,2-dihydropyrimidin-1-yl)-2-deoxy-2,, 2-difluororibose hydrochloride,, 103882-84-4, 2'-deoxy-2',, 2'-difluorocytidine hydrochloride,, 2'deoxy-2',, 47762,, 613327,, dFdC,, dFdCyd,, difluorodeoxycytidine hydrochloride,, gemcitabine,, Gemzar,, LY-188011 vaccine: gemcitabine hydrochloride

    Trial Purpose

    This pilot clinical trial studies the safety of a dendritic cell vaccine when given with
    gemcitabine hydrochloride in treating patients with breast cancer that has spread beyond the
    breast and local lymph nodes to other organs in the body. The vaccine is made up of natural
    cells found in the blood, called dendritic cells, and peptides, or small fragments of
    protein which are loaded onto the dendritic cells. This combination may help activate the
    immune system against stromal cells, which are cells that help cancer cells survive in the
    body. Gemcitabine hydrochloride is a chemotherapy drug that is given before the vaccine to
    help shrink the tumor and control cells that may interfere with the activity of the vaccine.
    Interfering with the stromal cells that help support the growth of cancer cells may lead to
    the death of the cancer cells.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. Assess the safety of gemcitabine hydrochloride (GEM) + alpha-type-1 dendritic cell
    (DC1)-tumor blood vessel antigen (TBVA) vaccination (tumor blood vessel antigen
    peptide-pulsed alpha-type-1 polarized dendritic cell vaccine).

    II. Assess the clinical response of metastatic breast cancer (MBC) to GEM + DC1-TBVA
    vaccination.

    III. Determine the clinical efficacy of GEM + DC1-TBVA vaccination in generating T-helper 1
    cell (Tc1) immunity.

    IV. Correlate changes in myeloid-derived suppressor cells (MDSC) and regulatory T cells
    (Tregs) with the generation of anti-TBVA T-cell immunity.

    OUTLINE:

    Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and
    8. Treatment repeats every 21 days for 3 courses. Beginning 3, 7, or 10 days later, patients
    receive tumor blood vessel antigen peptide-pulsed alpha-type-1 polarized dendritic cell
    vaccine intradermally (ID) followed by a second vaccination 7 days later. Courses may repeat
    after at least 4 weeks in the absence of disease progression or unacceptable toxicity.

    After completion of study treatment, patients are followed up for 30 days.

    Trial Arms

    Name Type Description Interventions
    vaccine: gemcitabine hydrochloride Experimental Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 3 courses. Beginning 3, 7, or 10 days later, patients receive tumor blood vessel antigen peptide-pulsed alpha-type-1 polarized dendritic cell vaccine ID followed by a second vaccination 7 days later. Courses may repeat after at least 4 weeks in the absence of disease progression or unacceptable toxicity. gemcitabine hydrochloride

    Eligibility Criteria

    Inclusion Criteria:

    - Patients must be human leukocyte antigen (HLA)-A2+

    - Histologically confirmed breast cancer

    - Patients must have evidence of metastatic disease measurable by Response Evaluation
    Criteria in Solid Tumors (RECIST) criteria or non-measurable lytic or mixed (lytic +
    blastic) bone lesions in the absence of measurable disease; Note: Measurable lesions
    include lytic or mixed (lytic + blastic) bone lesions, with an identifiable 10 mm
    soft tissue component that meets the measurability criteria per RECIST

    - There is no limit to the number of prior systemic treatment regimens

    - Patients must have a life expectancy of > 3 months

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

    - Patients must be at least 4 weeks from radiation therapy and recovered from all
    related toxicity

    - Prior GEM therapy is acceptable as long as the last dose was >= 3 months from
    registration on this study

    - Patients may have treated and stable brain metastases; they must be off steroids and
    must have had stable brain metastases for at least 6 months

    - White blood cell (WBC) > 3.0 x 10^9/L

    - Platelets > 100 x 10^9/L

    - Hemoglobin (Hgb) >= 10.0 gm/dl

    - Creatinine < 1.5 mg/dl

    - Bilirubin (total) < 2.0 ml/dl

    - Aspartate aminotransferase (AST) < 5.0 x normal institutional limits

    - Alkaline phosphatase < 2.5 upper limit of normal (ULN) (< 10 x ULN in presence of
    bone metastases)

    - Serum calcium =< 12 mg/dl

    - International normalized ratio (INR) < 1.5, except for subjects receiving warfarin
    therapy; for subjects who are receiving warfarin for prophylaxis or treatment of
    thrombosis, INR values should be carefully monitored while patients are on study

    - All patients must be informed of the investigational nature of this study and must
    provide written informed consent in accordance with institutional and federal
    guidelines; a copy of the informed consent document signed by the patient must be
    given to the patient

    - Patients must have a negative pregnancy test by urinalysis

    - Use of an effective means of contraception (men and women) is mandated in subjects of
    child-bearing potential; female subjects will be advised that they not become
    pregnant for at least one month after completing participation in the study; avoiding
    sexual activity is the only certain method to prevent pregnancy; however, if subjects
    choose to be sexually active, they should use an appropriate "double barrier" method
    of birth control (such as female use of a diaphragm, intrauterine device [IUD], or
    contraceptive sponge, in addition to male use of a condom) or the use of prescribed
    "birth control" pills, injections, or implants

    Exclusion Criteria:

    - HLA-A2 negative patients

    - Prior surgery, radiation therapy, or systemic therapy within 4 weeks of starting the
    study treatment

    - Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
    (AIDS)-related illness

    - Presence of bleeding diathesis

    - Current treatment on another clinical trial

    - Patients with organ allografts

    - Pregnancy or breast-feeding; female patients must be surgically sterile or be
    post-menopausal, or must agree to use effective contraception during the period of
    therapy; all female patients with reproductive potential must have a negative
    pregnancy test (serum or urine) prior to enrollment; male patients must be surgically
    sterile or must agree to use effective contraception during the period of therapy;
    the definition of effective contraception will be based on the judgment of the
    principal investigator or a designated associate

    - Other severe acute or chronic medical or psychiatric conditions, or laboratory
    abnormality that may increase the risk associated with study participation or study
    drug administration, or may interfere with the interpretation of study results, and
    in the judgment of the investigator would make the patient inappropriate for entry
    into this study

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Number of toxicities

    Secondary Outcome Measures

    mean change in Type-1 immune function

    Number of patients with clinical response

    Trial Keywords

    vaccine

    breast cancer

    metastatic