Trial Information

Neoadjuvant Intratumoral Injection of Dendritic Cells in Breast Cancer Translation of Biotechnology Into the Clinic

OBJECTIVES:

- Assess the safety of intratumoral (IT) autologous dendritic cell (DC) injection in
women with stage II or III breast cancer receiving neoadjuvant paclitaxel,
cyclophosphamide, and doxorubicin hydrochloride followed by surgery with or without
adjuvant radiotherapy and/or hormone therapy.

- Determine the clinical and pathologic response in patients treated with this regimen.

- Determine the immune response, in terms of tumor cell apoptosis and the presence and
characterization of tumor infiltrating white blood cells in resected breast cancer, in
patients treated with this regimen.

- Determine if IT DC injections administered during neoadjuvant chemotherapy-induced
tumor cell apoptosis can induce T-cell responses to tumor antigens in these patients.

OUTLINE: This is an open-label study.

- Leukapheresis: Patients undergo leukapheresis at baseline to collect peripheral blood
mononuclear cells for dendritic cell (DC) culture.

- Neoadjuvant, dose-dense chemotherapy: Patients receive paclitaxel IV over at least 3
hours on day 1 and filgrastim (G-CSF) subcutaneously (SC) on days 4-14 or pegfilgrastim
SC on day 2. Treatment repeats every 2 weeks for up to 4 courses in the absence of
disease progression or unacceptable toxicity.

Beginning 2 weeks after completion of paclitaxel chemotherapy, patients receive
cyclophosphamide IV and doxorubicin hydrochloride IV on day 1 and G-CSF SC on days 4-14 or
pegfilgrastim SC on day 2. Treatment repeats every 2 weeks for up to 4 courses in the
absence of disease progression or unacceptable toxicity.

- Intratumoral injection of autologous DCs: Intratumoral autologous DCs are injected into
the primary breast mass or palpable axillary node on day 7 of the 1st, 2nd, and 3rd
courses of paclitaxel chemotherapy. If no tumor can be localized by ultrasound after a
course of chemotherapy, the DCs are then injected into the site of the tumor bed
previously localized by clip or marker. In the event that the previously injected
primary tumor cannot be localized by ultrasound, a palpable lymph node, if still
present, should be injected rather than the tissue next to the primary tumor clip or
marker.

- Definitive breast surgery: Within 2-4 weeks after completion of neoadjuvant
chemotherapy, patients undergo modified radical mastectomy or lumpectomy with or
without standard axillary node dissection.* NOTE: *Standard axillary node dissection is
only required if no node assessment was done prior to chemotherapy or if the
pre-chemotherapy sentinel node was positive.

- Radiotherapy: Patients undergoing lumpectomy or those with residual disease requiring
chest wall radiotherapy after mastectomy (e.g., T3 or T4 breast lesions or 4 or more
axillary lymph nodes) undergo radiotherapy 2-4 weeks after surgery.

- Hormone therapy: Patients with estrogen and/or progesterone receptor-positive tumors
receive adjuvant hormone therapy for ≥ 5 years. Premenopausal patients receive
tamoxifen citrate and post- or perimenopausal patients receive either tamoxifen citrate
or an aromatase inhibitor (AI), or both of these drugs in sequence, as determined by
the treating oncologist.

Peripheral blood samples are obtained during each DC injection, at staging/biopsy, and then
periodically for up to 2 years. Blood samples are analyzed by ELISPOT and ELISA assays for
evaluation of immune response.

Tumor tissue is obtained by core biopsy of the breast primary and/or palpable axillary lymph
node at baseline and again after completion of paclitaxel chemotherapy. Tumor tissue is
analyzed by IHC and RT-PCR for COX-2 and VEGF-A and -C expression levels, as well as T-cell
and DC infiltration of the tumor. T-cell and DC infiltration is evaluated for correlation
with clinical outcomes at diagnosis, at the midpoint biopsy following paclitaxel
chemotherapy, and at definitive surgery.

After completion of study therapy, patients are followed periodically for up to 2 years.