Neoadjuvant/Adjuvant Chemotherapy, Vaccine & Adjuvant Radiation Therapy in p53-Overexpressing Stage III Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Drugs
      used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, work in
      different ways to stop tumor cells from dividing so they stop growing or die. Radiation
      therapy uses high-energy x-rays to damage tumor cells. Giving vaccine therapy before and/or
      after chemotherapy and radiation therapy may cause a stronger immune response.

      PURPOSE: This randomized phase I/II trial is studying the side effects of two regimens of
      vaccine therapy and to see how well they work in treating women who are receiving neoadjuvant
      or adjuvant chemotherapy and adjuvant radiation therapy for stage III breast cancer that
      overexpresses p53.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the safety and toxicity of two different schedules of vaccination comprising
           p53-infected autologous dendritic cells in women with p53-overexpressing stage III
           breast cancer undergoing neoadjuvant or adjuvant chemotherapy and adjuvant radiotherapy.

        -  Determine the immune response, in terms of humoral and cellular response, in patients
           treated with these regimens.

        -  Determine antigen-specific immune responses in patients treated with these regimens.

      OUTLINE: This is a randomized, open-label study. Patients are randomized to 1 of 2 treatment
      arms.

      All patients undergo apheresis for the collection of peripheral blood monocytes that are
      cultured with interleukin-4 and sargramostim (GM-CSF) to produce dendritic cells. The
      dendritic cells are infected with a recombinant adenoviral vector containing the wild-type
      p53 gene.

      Patients receive doxorubicin IV and cyclophosphamide IV every 2 weeks for 8 weeks (4 courses)
      followed 2 weeks later by paclitaxel IV every 2 weeks for 8 weeks (4 courses). Patients with
      stage III disease then undergo surgery. Three weeks after completion of paclitaxel (or after
      surgery for patients with stage III disease), patients undergo radiotherapy once daily for
      6.5 weeks. Patients are then receive vaccine therapy as per the arm to which they were
      randomized.

        -  Arm I: Patients receive vaccination comprising p53-infected autologous dendritic cells
           subcutaneously (SC) 1 week after completion of doxorubicin and cyclophosphamide, 1 week
           after completion of paclitaxel (or after surgery for patients with stage III disease),
           and at 6 and 12 weeks after completion of radiotherapy (for a total of 4 vaccinations).

        -  Arm II: Patients receive vaccination comprising p53-infected autologous dendritic cells
           SC at 6, 8, 10, and 12 weeks after completion of radiotherapy.

      Treatment in both arms continues in the absence of unacceptable toxicity.

      Patients are followed at 1 month, every 3 months for 2 years, every 6 months for 3 years, and
      then annually thereafter.

      PROJECTED ACCRUAL: A total of 20-50 patients (10-25 per treatment arm) will be accrued for
      this study within 2 years.
    

Intervention name(s): autologous dendritic cell-adenovirus p53 vaccine
Intervention type(s): Biological
Intervention description(s): Given subcutaneously on one of two schedules
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage IIIA breast cancer; stage IIIB breast cancer