A Phase I Vaccine Safety and Chemotherapy Dose-Finding Trial of an Allogeneic GM-CSF-Secreting Breast Cancer Vaccine Given in a Specifically Timed Sequence With Immunomodulatory Doses of Cyclophosphamide and Doxorubicin
- Determine the safety of vaccination comprising allogeneic sargramostim
(GM-CSF)-secreting breast cancer cells with or without immunomodulation using
cyclophosphamide and doxorubicin in women with stage IV breast cancer.
- Determine the doses of cyclophosphamide and doxorubicin that maximize vaccine-induced
immunity, in terms of immune response to HER2/neu, in patients treated with these
- Compare in vivo immune response induced by these regimens, as measured by
immunohistochemical analysis of vaccine site biopsies from these patients, with
responses seen in prior preclinical and clinical studies.
- Determine the time to disease progression in patients treated with these regimens.
OUTLINE: This is a dose-finding study.
The first 6 patients receive 1 of 2 doses of vaccine comprising allogeneic sargramostim
(GM-CSF)-secreting breast cancer cells intradermally (ID) on day 0. Subsequent patients
receive cyclophosphamide IV on day -1, vaccine at the higher dose ID on day 0, and
doxorubicin IV on day 7. Treatment in all patients repeats every 4-6 weeks for 3 courses in
the absence of disease progression or unacceptable toxicity. Patients with stable or
responding disease after the third course receive a fourth course of treatment at
approximately 4 months after completion of the third course.
Cohorts of 2-3 patients receive a fixed dose of vaccine in combination with escalating doses
of doxorubicin and cyclophosphamide. Doses of cyclophosphamide and doxorubicin are escalated
until an optimal dose of combination chemotherapy with a fixed dose of vaccine is achieved.
Patients are followed at 1 month and 4 months after completion of study therapy and then
PROJECTED ACCRUAL: A total of 6-60 patients will be accrued for this study.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Toxicity of vaccine w/ & w/o cyclophosphamide+doxorubicin by history and phys. exam. at 28-42 days after each vaccination, 56-84 days after third vaccination, 6 months after first vaccination, and annually after first vaccination
Leisha A. Emens, MD, PhD
Sidney Kimmel Comprehensive Cancer Center
United States: Food and Drug Administration
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
|Baltimore, Maryland 21231-2410