Trial Information

1) Adenovirus p53 Infected DC Vaccine For Breast Cancer, 2) Translation of Biotechnology Into the Clinic

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.