A Phase I/II Study of Neoadjuvant Photodynamic Immunomodulation for Colon Cancer
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 试验地点
- 2
- 主要终点
- Efficacy
研究概览
简要总结
The central hypothesis for this study is that it is safe and feasible to administer intraluminal photodynamic therapy (PDT) to colon cancers by colonoscopy to induce localized inflammatory/immune response. The objective is to demonstrate the feasibility and safety of PDT to colon cancer patients administered before surgery and to characterize the inflammatory/immune response at the tumor site and systemically. The long-term objective of these studies is to modify he natural biology of colorectal cancers and improve patient survival.
详细描述
The central hypothesis for this study is that it is safe and feasible to administer intraluminal photodynamic therapy (PDT) to colon cancers, via colonoscopy, in the neoadjuvant setting to induce localized tumor cell death and an inflammatory/immune response with an increased Th1 component, utilizing 5-ALA as a photosensitizer. The objective is to conduct an initial phase I/II clinical study to demonstrate the feasibility and safety of colonoscopic, neoadjuvant intraluminal PDT to colon cancer patients administered 96 hours pre-resection, to characterize the inflammatory/immune response at the PDT treated tumor site, and to evaluate the systemic anti-tumor immune response. The long-term objective of these studies is to provide an easily administered, adjunctive, therapeutic maneuver that lacks systemic toxicity, with the potential to modulate the natural biology of colorectal cancers that have not elicited a favorable anti-tumor immune response and to improve patient survival.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Patients must have a histologically proven diagnosis of colorectal cancer.
- •Have clinical stage I, II, or III disease.
- •Expected survival must be greater than twelve (12) months.
- •A Karnofsky Performance Status (KPS) must be 70 or greater (Appendix I).
- •Patients must be >21 years of age.
- •No prior therapy.
- •Female patients must not be lactating and must be surgically sterile (via hysterectomy or bilateral tubal ligation), postmenopausal, or using acceptable methods of contraception if they are of child bearing potential. Female patients of childbearing potential must also have a negative serum pregnancy test.
- •Patients must be able to understand and sign an informed consent form, which must comply with U.S. regulations (U.S. 21 CFR 50) and ICH guidelines.
- •Eligible patients must have adequate initial hematologic and coagulation parameters, hemoglobin ≥ 11g/dl, platelet count >50,000, Protime and Prothrombin Time ≤ 1.5 x normal.
- •Eligible patients must have adequate bone marrow, liver and renal function: ANC > 1500/μL, Platelets >100,000 x μL, total bilirubin < the upper limit of normal (ULN), and creatinine clearance (CrCl) > 45 mL/min
排除标准
- •Any co-morbidity that precludes primary surgical resection of the colorectal tumor.
- •Any significant general organ system compromise including:
- •Liver function, transaminases ≥ 2 x,
- •Renal function, Cr ≥ 1.5 x upper limit of normal
- •Pulmonary function, room air O2 saturation <90%
- •Cardiovascular function, Patients with significant (Class III or IV) cardiovascular disease according to the New York Heart Association's functional criteria (Appendix II)
- •Gastrointestinal function, i.e. active inflammatory bowel disease or active peptic ulcer disease.
- •Any contraindication to repeat colonoscopy, such as idiosyncratic reactivity to conscious sedation medications.
- •Prior treatment for the diagnosis of colorectal cancer, including surgical resection.
- •Stage IV colorectal cancer, i.e. the clinical presence of metastases
- •Prior malignant diagnosis except for the basal cell epithelioma of the skin.
- •Persistent fever greater than 38 C.
- •Mineral overload syndromes for Lead, Zinc, Copper or Iron.
- •Use of any agent that modulates 5-ALA metabolism and porphyrin synthesis, e.g. St. John's Wort.
- •Required use of corticosteroids or immune suppression for any reason including an organ allograft or HIV infection
- •Patients with any acute or chronic illness including cardiovascular disease (e.g. history of atrial fibrillation or ventricular arrhythmias) or history of myocardial infarction, autoimmune state, or any psychiatric illness that in the opinion of the Investigators would compromise treatment.
- •Use of investigational drugs within 30 days of execution of the informed consent form.
研究组 & 干预措施
PDT
Participants receive neoadjuvant 5-ALA and PDT.
干预措施: PDT with 5-ALA radiosensitization (Drug)
结局指标
主要结局
Efficacy
时间窗: 6 months
Define biologic efficacy of PDT in relation to generation of an immune response at the tumor site and systemically. This will be measured by degree of dendritic cell infiltration into tumor and regional lymph nodes, and degree of systemic immunity directed against colon cancer antigens immediately post procedure and after 6 months.
Safety
时间窗: 6 months
Safety will be evaluated from enrollment through 6 months. This will be measured by proportion of patients completing planned surgery, proportion of patients experiencing grade 3 or 4 toxicities, and lack of observation of serious adverse events related to the study procedure.
次要结局
- Quality of Life(6 months after completion of participation)
- Sustained immunity(1.5-6 months post completion of participation)
研究者
Edward Nelson
Dr. Edward Nelson
University of California, Irvine