A Phase I Clinical Trial of Autologous Dendritic Cell Vaccine for Recurrent Ovarian or Primary Peritoneal Cancer
This study is open to women with recurrent epithelial ovarian carcinoma or primary peritoneal cancer. Subjects will be asked to donate either a piece of their tumor or malignant effusion in order to make the first part of the vaccine or lysate. If enough of the lystate had been collected to make the first part of the vaccine, then subjects may enroll in the study as long as they meet the rest of the entry criteria.
After is determined that a subject is eligible to enroll into the study, you will have to donate some blood in order to make the second part of the vaccine. After this, the blood and vaccine are mixed together to make the vaccine called DCVax-L. You will be given two dose of a drug called Avastin every other week (Avastin will be given through your vein) and a oral chemotherapy called Cytoxan. One week after your last dose of oral Cytoxan, you will receive 3 vaccines given every other week for the next month. After the first two doses of vaccine, you will also receive more Avastin. During the study you will be seeing your study team to have physical exams, blood drawn in order to monitor your health and have blood drawn for research. The study team will contact you for the next 5 years in order to determine how you are doing.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Clinical Trial of Autologous Dendritic Cell Vaccine Leaded With Autologous Tumor Cell Lysate for Recurrent Ovarian or Primary Peritoneal Cancer|
- 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. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- To assess the immunogenicity of DCVax-L administered intradermally in patients with recurrent ovarian or recurrent primary peritoneal cancer, combined with intravenous bevacizumab and oral metronomic cyclophosphamide. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||November 2007|
|Study Completion Date:||December 2009|
|Primary Completion Date:||December 2009 (Final data collection date for primary outcome measure)|
Subjects with stage II to IV recurrent epithelial ovarian carcinoma or recurrent primary peritoneal cancer, from whom solid tumor, ascites or pleural effusion will be harvested and available and sufficient for lysate preparation; and whose largest tumor nodule is ≤ 2.5 cm. Subjects may have undergone chemotherapy or other therapy following tumor harvesting and prior to enrollment (apheresis).
Subjects will receive three doses of intradermal vaccination with ~5-10 x 106 dendritic cells (DCVax-L) on days 0, 14 and 28
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00683241
|United States, Pennsylvania|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||George Coukos, M.D., Ph.D.||University of Pennsylvania|