Genistein Combined With FOLFOX or FOLFOX-Avastin for Treatment of Metastatic Colorectal Cancer: Phase I/II Pilot Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Number of Adverse Events
研究概览
简要总结
Colorectal neoplasms are the third most common malignancies in the United States. Patients with metastatic (stage IV) colorectal cancer have a median life expectancy of 2 years. The response rates to chemotherapy range from 35-40%.
Epidemiologic evidence suggests that soy compounds may reduce the incidence of colorectal cancers. Laboratory analyses demonstrate that genistein, a soy-derived compound, may inhibit Wnt signaling, a pathway activated in majority of colorectal cancers. Laboratory observations also demonstrate that genistein may augment growth inhibition when combined with chemotherapeutic agents of 5-Fluorouracil and platinum compounds.
Based on pre-clinical data the investigators hypothesize that combining genistein with the standard of care chemotherapeutic regimens will reduce chemotherapy resistance and improve response rates in patients. The aim of the study is to add genistein to the regimens of FOLFOX or FOLFOX-Avastin in patients with newly diagnosed stage IV colon or rectal neoplasms.
详细描述
OBJECTIVES:
Primary
- Evaluate the tolerability of genistein when combined with chemotherapy
Secondary:
- Evaluate Response Rate (RR) as measured by the radiologic RECIST criteria
- Evaluate Progression Free Survival (PFS)
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
- •Adult male and female patients ≥18 years old
- •Have pathologically confirmed colon or rectal carcinoma
- •Have metastatic (stage IV) disease
- •Have a plan by treating physician to receive FOLFOX or FOLFOX-Avastin
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤2
- •Have adequate hematopoietic, hepatic and renal function
- •Hematopoietic function
- •Hemoglobin ≥10g/dL
- •Absolute Neutrophil Count(ANC) ≥1,500cells/mm2
- •Platelet Count ≥100,000/µL
- •Hepatic Function
- •Total bilirubin ≤ 1.5x the upper limit of normal
- •ALT and AST must each be ≤2,5x the upper limits of normal
- •Renal Function
- •Estimated creatinine clearance (Clcr) ≥30 mL/minute
- •Are not pregnant and do not plan to become pregnant
排除标准
- •Prior systemic chemotherapy for metastatic disease
- •History of breast cancer, endometrial cancer or ovarian cancer or taking aromatase inhibitors or selective estrogen receptor modulators
- •Patients taking MAO-inhibitors
- •History of myocardial infarctions or cardiac stent placement less than 1 year before recruitment into the study
- •Unable to give informed consent or comply with clinical trial requirements
- •Uncontrolled hypertension
- •History of clinically significant GI bleeding within prior 2 months prior to enrollment
- •Presence of GI fistula
- •Prior history of bowel perforation
- •History of CNS thrombotic/embolic or ischemic events
- •Have past or current, acute or chronic concurrent medical condition/illness or therapy that, in the opinion of the investigator, would make the subject unsuitable for the clinical trial or unable to comply with the follow up visits.
研究组 & 干预措施
Genistein
Genistein combined with FOLFOX or FOLFOX-Avastin Genistein 60mg/day orally for 7 days every 2 weeks. Genistein will be administered beginning 4 days prior to FOLFOX or FOLFOX-Avastin and continuing the 3 days of chemotherapy.
干预措施: Genistein (Drug)
结局指标
主要结局
Number of Adverse Events
时间窗: up to 6 months
Number of adverse events to assess tolerability of genistein treatment. Evaluation of side effects conducted every 14 days before each chemotherapy/genistein cycle.
Percent Change in Tumor Size
时间窗: end of Cycle 6
Percent change in tumor size after cycle 6. Each cycle is 21 days.
次要结局
- Response Rate RECIST Criteria(end of Cycle 6)
- Number of Participants With an Overall Response Rate (ORR)(up to 50 months)
- Best Overall Response Rate RECIST Criteria(up to 50 months)
- Number of Participants With Best Overall Response Rate (ORR)(up to 50 months)
- Progression Free Survival (PFS)(up to 50 months)
- Percent of Patients With Progression Free Survival (PFS) at 6 Months and 12 Months(6 month and 12 month)
- Overall Survival (OS)(up to 50 months)
研究者
Sofya Pintova
Assistant Professor
Icahn School of Medicine at Mount Sinai