Safety Study Of Chemotherapy Combined With Dendritic Cell Vaccine to Treat Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

Intervention name(s): LA TNBC: DC vaccine+Preop chemo; ER+/HER2-BC:DC vaccine+Preop chemo
Intervention type(s): Biological; Biological
Intervention description(s): 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 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.
Other intervention name(s): DC Vaccine - Dendritic Cell Vaccine; Preop chemo: Doxorubicin; Preop chemo: cyclophosphamide; Preop chemo: Paclitaxel; Preop chemo: Carboplatin; DC Vaccination - Dendritic cell vaccination; Preop chemo - doxorubicin; Preop chemo - cyclophosphamide; Preop chemo - paclitaxel; Preop chemo: Carboplatin
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Cyclophosphamide; Carboplatin; Doxorubicin; Liposomal doxorubicin; Vaccines
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Dendritic cell vaccine; Breast Cancer; Doxorubicin; Paclitaxel; Cyclophosphamide; Carboplatin