Finding studies
Finding studies
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Lead
National Cancer Institute (NCI)
Background: * Monocytes can differentiate into classic M1 (classically activated) macrophages inhibiting tumor proliferation and promoting natural killer (NK) cell differentiation. * Human alpha interferons (interferon alfa, IFN-alpha), interferon gamma (IFN-gamma) and monocytes have strong anti-neoplastic response in vitro and in vivo * IFN-alpha and IFN-gamma have been shown in early phase clinical trials to be safely administered intraperitoneally. * Intraperitoneal monocytes alone or activated with IFN-gamma are safe and feasible as demonstrated in phase I clinical studies. * We have shown that the combination of human monocytes, IFN-alpha2a and IFN-gamma1b, or pegylated IFN-alpha, act synergistically against tumor cells in vitro and in mouse models. Objectives: -To identify a maximum tolerated dose of intraperitoneal autologous monocytes and Sylatron(R) (Peginterferon alfa-2b) and Actimmune(R) (Interferon gamma-1b). Eligibility: * Advanced metastatic or unresectable epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer that is relapsed and resistant or refractory to prior platinum-based standard care systemic regimen. * Patients must be off prior chemotherapy, radiation therapy, hormonal therapy or biological therapy for at least 4 weeks. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 and adequate organ and marrow function. Design: * This is an open label single arm phase I trial to determine the maximum tolerated dose of intraperitoneal monocytes and Sylatron(R) (Peginterferon alfa-2b) and Actimmune(R) (Interferon gamma-1b). * Autologous monocytes obtained through apheresis will be mixed with Sylatron(R) (Peginterferon alfa-2b) and Actimmune(R) (Interferon gamma-1b) in a 3 + 3 dose escalation and administered intraperitoneally once every 28 days. A new product will be manufactured for each treatment cycle. * Once the maximum tolerated dose is obtained, an expansion cohort will be enrolled to better quantify response rate and time to disease progression. * Research samples including peripheral blood and ascites will be obtained prior to the initiation of study therapy andprior to the start of each cycle. Tissue biopsies will be obtained in the dose expansion phase to characterize the immune infiltration. * Patients will be evaluated every 2 cycles for response using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and every cycle for safety using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Age
18–any
Sex
FEMALE
Healthy volunteers
Not accepted
