A Phase I Clinical Trial of Autologous Dendritic Cell Vaccine Leaded With Autologous Tumor Cell Lysate for Recurrent Ovarian or Primary Peritoneal Cancer
Subjects with recurrent epithelial ovarian carcinoma or recurrent primary peritoneal cancer,
for whom autologous tumor or malignant effusion has been harvested and is available for
lysate preparation, are eligible, provided all other eligibility criteria are fulfilled.
Harvested tumor or malignant effusion will be shipped to Cognate BioServices (Sunnyvale, CA)
for preparation of lysate. If sufficient amount of lysate for vaccine can be generated,
subjects will be enrolled to the study.
Subjects will undergo apheresis on day -35 to -29 to harvest peripheral blood mononuclear
cells (PBMC). The apheresis product will be shipped to Cognate BioServices, where DC will be
prepared and pulsed with autologous lysate according to proprietary technology. Following
apheresis, subjects will receive two cycles of biological antiangiogenesis/immunomodulatory
therapy comprising intravenous bevacizumab at 10 mg/kg on day -28 and -14, which may be
followed by 7 days of oral metronomic cyclophosphamide at 50 mg daily (days -28 to -21, and
-14 to -7, respectively). Subjects will receive three doses of intradermal vaccination with
~5-10 x 106 dendritic cells (DCVax-L) on days 0, 14 and 28. Subjects will also receive
intravenous bevacizumab at 10 mg/kg concurrently with intradermal DCVax-L on day 0 and 14,
which may be followed by oral cyclophosphamide at 50 mg for 7 days (days 0 to 7, and 14 to
21, respectively). The last DCVax-L (day 28) may be followed by oral cyclophosphamide at 50
mg daily x 7 days (days 28 to 35), but no bevacizumab will be given on day 28. Prevnar, an
FDA approved seven-valent vaccine against Pneumococcus pneumoniae, will be given
intramuscularly on day 0 as positive control of immune responsiveness. Two weeks following
third vaccine dose (day 42), patients will undergo immune assessment.
Subjects will be contacted every 6 months for 5 years and then annually for survival.
Subject will have the option of enrolling in other combinatorial immunotherapy trials when
these are available, if they satisfy enrollment criteria. Subjects will have the option of
continuing vaccination every two months till exhaustion of DCVax-L or disease progression,
whichever occurs first.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the feasibility and safety of administering DCVax-L intradermally combined with intravenous bevacizumab and oral metronomic cyclophosphamide in patients with recurrent ovarian or primary peritoneal cancer.
George Coukos, M.D., Ph.D.
University of Pennsylvania
United States: Food and Drug Administration
|University of Pennsylvania||Philadelphia, Pennsylvania 19104|