A Phase II Study of Active Immunotherapy With PANVAC or Autologous, Cultured Dendritic Cells Infected With PANVAC After Complete Resection of Hepatic or Pulmonary Metastases of Colorectal Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 74
- 试验地点
- 6
- 主要终点
- Recurrence-free Survival at 2 Years
研究概览
简要总结
RATIONALE: Vaccines made from a gene-modified virus and a person's white blood cells may make the body build an effective immune response to kill tumor cells. Biological therapies, such as Granulocyte-macrophage colony-stimulating factor (GM-CSF), may stimulate the immune system in different ways and stop tumor cells from growing. Combining different types of biological therapies may kill more tumor cells.
PURPOSE: This randomized phase II trial is studying giving vaccine therapy together with dendritic cells to see how well it works compared to giving vaccine therapy together with GM-CSF in treating patients with liver or lung metastases from colorectal cancer removed by surgery.
详细描述
OBJECTIVES:
Primary
- Compare 2-year disease-free survival of patients with completely resected hepatic or pulmonary metastases secondary to colorectal cancer treated with adjuvant vaccine therapy comprising vaccinia-Carcinoembryonic antigen (CEA)-mucin 1 (MUC-1)- Triad of costimulatory molecules TRICOM vaccine (PANVAC-V) and fowlpox-CEA-MUC-1-TRICOM vaccine (PANVAC-F) administered with autologous dendritic cells or with sargramostim (GM-CSF).
Secondary
- Compare the rate and magnitude of immune response, as determined by enzyme-linked immunosorbent spot (ELISpot), in patients treated with these regimens.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed hepatic or pulmonary metastases secondary to adenocarcinoma of the colon and rectum
- •Must have undergone complete resection of hepatic or pulmonary metastases with curative intent
- •No evidence of gross residual disease after surgery
- •One or more resected and ablated lesions allowed provided all gross residual tumor was destroyed by ablation
- •Repeated resections of hepatic metastatic disease or resections of extrahepatic metastases prior to resection of the hepatic metastases allowed provided the most recent hepatic metastatic resection included total disease resection and/or ablation
- •Must have received at least 2 months of perioperative systemic chemotherapy (including preoperative and/or postoperative chemotherapy) that was completed at least 1 month ago
- •PATIENT CHARACTERISTICS:
- •At least 18
- •Performance status
- •Karnofsky 70-100%
- •Life expectancy
- •At least 6 months
- •Hematopoietic
- •Platelet count ≥ 75,000/mm^3
- •Hemoglobin ≥ 8.5 g/dL (transfusion or epoetin alfa allowed)
- •Bilirubin ≤ 2.0 mg/dL
- •Hepatitis B surface antigen negative
- •Hepatitis C antibody negative
- •No other serious chronic or acute hepatic disease
- •Creatinine ≤ 1.5 mg/dL OR
- •Creatinine clearance > 60 mL/min
- •Cardiovascular
- •No New York Heart Association class III or IV cardiac disease
- •No other serious chronic or acute cardiac disease
- •No asthma
- •No chronic obstructive pulmonary disease
- •No other serious chronic or acute pulmonary disease
- •Immunologic
- •No history of autoimmune disease, including, but not limited to, any of the following:
- •Inflammatory bowel disease
- •Systemic lupus erythematosus
- •Ankylosing spondylitis
- •Scleroderma
- •Multiple sclerosis
- •No human immunodeficiency virus (HIV) infection by enzyme-linked immunosorbent assay (ELISA) and western blot
- •Not immunocompromised (by disease or therapy)
- •No allergy to eggs or any component of the study vaccine
- •No history of allergy or untoward reaction to prior vaccinia (smallpox) vaccination
- •No allergy or untoward reaction to sargramostim (GM-CSF)
- •No active acute or chronic infection, including urinary tract infection within the past 72 hours
- •No inflammatory bowel conditions, including, but not limited to, the following:
- •Active infectious enteritis
- •Eosinophilic enteritis
- •No acute, chronic, or exfoliative skin disorders, including any of the following:
- •Extensive psoriasis
- •Disseminated zoster
- •Varicella zoster
- •Severe acne
- •Other open rashes or wounds
- 另有 23 项未显示
排除标准
- 未提供
研究组 & 干预措施
PANVAC-V + PANVAC-F + DC
Patients undergo leukapheresis to obtain leukocytes for generation of autologous dendritic cells (DC). Patients then receive autologous DC loaded with vaccinia-CEA-MUC-1-TRICOM (PANVAC-V) vaccine subcutaneously (SC) and intradermally (ID) on day 1 and autologous DC loaded with fowlpox-CEA-MUC-1-TRICOM (PANVAC-F) vaccine SC and ID on days 28, 56, and 84.
干预措施: therapeutic autologous dendritic cells (Biological)
PANVAC-V + PANVAC-F + GM-CSF
Patients receive PANVAC-V SC on day 1 and PANVAC-F SC on days 28, 56, and 84. Patients also receive sargramostim (GM-CSF) SC into the same injection site once daily on days 0-3, 28-31, 56-59, and 84-87.
干预措施: inalimarev (Biological)
PANVAC-V + PANVAC-F + GM-CSF
Patients receive PANVAC-V SC on day 1 and PANVAC-F SC on days 28, 56, and 84. Patients also receive sargramostim (GM-CSF) SC into the same injection site once daily on days 0-3, 28-31, 56-59, and 84-87.
干预措施: sargramostim (Biological)
PANVAC-V + PANVAC-F + GM-CSF
Patients receive PANVAC-V SC on day 1 and PANVAC-F SC on days 28, 56, and 84. Patients also receive sargramostim (GM-CSF) SC into the same injection site once daily on days 0-3, 28-31, 56-59, and 84-87.
干预措施: falimarev (Biological)
PANVAC-V + PANVAC-F + DC
Patients undergo leukapheresis to obtain leukocytes for generation of autologous dendritic cells (DC). Patients then receive autologous DC loaded with vaccinia-CEA-MUC-1-TRICOM (PANVAC-V) vaccine subcutaneously (SC) and intradermally (ID) on day 1 and autologous DC loaded with fowlpox-CEA-MUC-1-TRICOM (PANVAC-F) vaccine SC and ID on days 28, 56, and 84.
干预措施: inalimarev (Biological)
PANVAC-V + PANVAC-F + DC
Patients undergo leukapheresis to obtain leukocytes for generation of autologous dendritic cells (DC). Patients then receive autologous DC loaded with vaccinia-CEA-MUC-1-TRICOM (PANVAC-V) vaccine subcutaneously (SC) and intradermally (ID) on day 1 and autologous DC loaded with fowlpox-CEA-MUC-1-TRICOM (PANVAC-F) vaccine SC and ID on days 28, 56, and 84.
干预措施: falimarev (Biological)
结局指标
主要结局
Recurrence-free Survival at 2 Years
时间窗: 2 years
Recurrence-free survival for randomized patients receiving dendritic cells (DC) loaded with PANVAC or PANVAC plus Granulocyte-macrophage colony-stimulating factor (GM-CSF) measured from the date of metastasectomy, with relapse defined as documented disease recurrence at any site.
次要结局
- Positive Immune Response as Measured by (Enzyme-linked Immunosorbent Spot) ELISpot Assay(13 weeks)
研究者
Michael Morse, MD
Professor of Medicine
Duke University