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Safety and Immunogenicity of a Personalized Synthetic Long Peptide Breast Cancer Vaccine Strategy in Patients With Persistent Triple-Negative Breast Cancer Following Neoadjuvant Chemotherapy

NCT02427581

Description:

The most important consideration in the design of this clinical trial is to ensure the safe translation of the personalized synthetic long peptide vaccine strategy. The Food and Drug Administration (FDA) dictates that initial studies of biologic therapies be performed in such a way that there is a balance between the potential risks and benefits in individual patients. Consistent with these recommendations, the investigators will target patients with triple-negative breast cancer who do not have a pathologic complete response after neoadjuvant chemotherapy. These patients typically have no gross evidence of disease following standard of care therapy (neoadjuvant chemotherapy, surgery and radiation therapy) but are at extremely high-risk for disease recurrence. Targeting this patient population provides a window-of-opportunity to design and manufacture the personalized cancer vaccines, maximizes the potential benefit from the vaccine as the regulatory networks associated with metastatic disease are not present, and balances risk in this patient population with extremely high risk for disease recurrence but no other treatment options.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Safety and Immunogenicity of a Personalized Synthetic Long Peptide <span class="go-doc-concept go-doc-disease">Breast Cancer</span> Vaccine Strategy in Patients With Persistent Triple-Negative <span class="go-doc-concept go-doc-disease">Breast Cancer</span> Following <span class="go-doc-concept go-doc-intervention">Neoadjuvant Chemotherapy</span>

Title

  • Brief Title: Safety and Immunogenicity of a Personalized Synthetic Long Peptide Breast Cancer Vaccine Strategy in Patients With Persistent Triple-Negative Breast Cancer Following Neoadjuvant Chemotherapy
  • Official Title: A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of a Personalized Synthetic Long Peptide Breast Cancer Vaccine Strategy in Patients With Persistent Triple-Negative Breast Cancer Following Neoadjuvant Chemotherapy
  • Clinical Trial IDs

    NCT ID: NCT02427581

    ORG ID: 201506113

    Trial Conditions

    Triple Negative Breast Cancer

    Triple Negative Breast Neoplasms

    Triple-Negative Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Poly ICLC Hiltonol Arm 1 - personlized synthetic long peptide vaccine

    Trial Purpose

    The most important consideration in the design of this clinical trial is to ensure the safe
    translation of the personalized synthetic long peptide vaccine strategy. The Food and Drug
    Administration (FDA) dictates that initial studies of biologic therapies be performed in
    such a way that there is a balance between the potential risks and benefits in individual
    patients. Consistent with these recommendations, the investigators will target patients with
    triple-negative breast cancer who do not have a pathologic complete response after
    neoadjuvant chemotherapy. These patients typically have no gross evidence of disease
    following standard of care therapy (neoadjuvant chemotherapy, surgery and radiation therapy)
    but are at extremely high-risk for disease recurrence. Targeting this patient population
    provides a window-of-opportunity to design and manufacture the personalized cancer vaccines,
    maximizes the potential benefit from the vaccine as the regulatory networks associated with
    metastatic disease are not present, and balances risk in this patient population with
    extremely high risk for disease recurrence but no other treatment options.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Arm 1 - personlized synthetic long peptide vaccine Experimental Each subject will receive a single synthetic long peptide vaccine on Days 1, 3, 5, 8, 43, 85, and 169. The first four injections must take place within the first 10 days, but the timing of the injections is flexible (+/- 2 days). The remaining injections (Days 43, 85, and 169) may be done within a +/- 2 week window surrounding each day. Each synthetic long peptide vaccine will be administered intramuscularly. Poly IC:LC will be co-administered with each of the synthetic long peptide vaccines. Each peptide vaccine will include 1 mg of synthetic long peptide (up to 7 peptides) resuspended in sterile water co-administered with 1.5 mg poly IC:LC. Poly ICLC

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically confirmed diagnosis of invasive breast cancer.

    - ER and PR less than Allred score of 3 or less than 1% positive staining cells in the
    invasive component of the tumor

    - HER2 negative by FISH or IHC staining 0 or 1+.

    - Consented for genome sequencing and dbGAP-based data sharing and has provided or will
    provide germline and tumor DNA samples of adequate quality for sequencing.

    - Clinical stage T2-T4c, any N, M0 primary tumor by AJCC 7th edition clinical staging
    prior to neoadjuvant chemotherapy, with residual invasive breast cancer after
    neoadjuvant therapy. If the patient has invasive cancer or DCIS in the contralateral
    breast, she is not eligible for this study.

    - At least 18 years of age.

    - Eastern Cooperative Oncology Group (ECOG) performance status 2

    - Adequate organ and marrow function no more than 14 days prior to registration as
    defined below:

    - WBC 3,000/L

    - absolute neutrophil count 1,500/L

    - platelets 100,000/L

    - total bilirubin 2.5 X institutional upper limit of normal

    - AST/ALT 2.5 X institutional upper limit of normal

    - creatinine 1.5 X institutional upper limit of normal

    - Women of reproductive potential must agree to use adequate contraception (hormonal or
    barrier method of birth control; abstinence) prior to study entry and for the
    duration of study participation.

    - Able to understand and willing to sign an IRB-approved written informed consent
    document.

    Exclusion Criteria:

    - Evidence of progressive breast cancer within the last 30 days.

    - Received chemotherapy, radiotherapy, or biologic therapy within the last 30 days
    (neoadjuvant chemotherapy excluded).

    - Experiencing adverse events due to agents administered more than 30 days earlier.

    - Receiving any other investigational agent(s) or has received an investigational agent
    within the last 30 days.

    - Known metastatic disease.

    - Invasive cancer or DCIS in the contralateral breast.

    - Known allergy, or history of serious adverse reaction to vaccines such as
    anaphylaxis, hives, or respiratory difficulty.

    - Uncontrolled intercurrent illness including, but not limited to ongoing or active
    infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
    arrhythmia (including sinus bradycardia), or psychiatric illness/social situation
    that would limit compliance with study requirements.

    - Prior or currently active autoimmune disease requiring management with
    immunosuppression. This includes inflammatory bowel disease, ulcerative colitis,
    Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis,
    hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic
    lupus erythematosus, Sjorgen's syndrome, sarcoidosis, or other rheumatologic disease
    or any other medical condition or use of medication (e.g., corticosteroids) which
    might make it difficult for the patient to complete the full course of treatments or
    to generate an immune response to vaccines. Asthma or chronic obstructive pulmonary
    disease that does not require daily systemic corticosteroids is acceptable. Any
    patients receiving steroids should be discussed with the PI to determine if eligible.

    - Pregnant or breastfeeding. A negative serum pregnancy test is required no more than 7
    days before study entry.

    - The patient with a previous history of non-breast malignancy is eligible for this
    study only if the patient meets the following criteria for a cancer survivor. A
    cancer survivor is eligible provided the following criteria are met: (1) patient has
    undergone potentially curative therapy for all prior malignancies, (2) patients have
    been considered disease free for at least 1 year (with the exception of basal cell or
    squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix).

    - Patient must have no active major medical or psychosocial problems that could be
    complicated by study participation.

    - Known HIV-positive status. These patients are ineligible because of the potential
    inability to generate an immune response to vaccines.

    - Subjects with a strong likelihood of non-adherence such as difficulties in adhering
    to follow-up schedule due to geographic distance from the Siteman Cancer Center
    should not knowingly be registered.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Safety of the vaccine regimen as measured by grade and frequency of adverse events

    Secondary Outcome Measures

    Immunogenicity of the vaccine regimen as measured by ELISPOT analyses

    Immunogenicity of the vaccine regimen as measured by multiparametric flow cytometry

    Trial Keywords