Phase II Randomized, Placebo-Controlled Trial of Linaclotide to Demonstrate Bioactivity in Patients With Sporadic Colorectal Adenomas and With Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 150
- 试验地点
- 6
- 主要终点
- Pharmacodynamics effect on cGMP levels
研究概览
简要总结
This phase II trial studies the how well linaclotide works in treating patients with stages 0-3 colorectal cancer. Linaclotide is a very small protein that binds to receptors on intestinal cells and makes them secrete water and salt.
详细描述
PRIMARY OBJECTIVES:
I. To determine whether, compared to placebo, linaclotide administered as a single oral daily dose x 7 days, induces a pharmacodynamics (PD) effect on cGMP levels, based on biopsy samples of adenomas or resected colorectal adenocarcinomas.
SECONDARY OBJECTIVES:
I. To compare Ki-67, guanylin levels and GUCY2C expression in adenomas and cancers versus normal tissue after exposure to linaclotide or placebo.
II. To confirm the safety and tolerability of linaclotide in sporadic adenoma and cancer patients.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •History of 1 or more sporadic colorectal adenoma on previous endoscopy (adenoma cohort) or stage 0-3 biopsy proven colorectal cancer (CRC) (colorectal cancer cohort) who are scheduled for a surgical procedure
- •Ability to understand and willingness to sign a written informed consent document and follow study procedures
- •Ability to swallow capsules without difficulty
- •Ability to maintain pill diaries
- •Willingness to employ adequate contraception for men and women of childbearing potential for the duration of the study. Acceptable methods include double barrier methods, intrauterine device (IUD), postmenopausal status, and/or documentation of surgical sterilization
- •Participants must have no chronic, clinically severe health issues which, in the opinion of their physician or the research team, could preclude trial activities including the one week drug exposure phase
排除标准
- •History of gastroparesis
- •History of celiac disease
- •Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
- •Microscopic colitis, including collagenous colitis
- •Has taken linaclotide within 30 days prior to consent
- •Any malignancy except colorectal cancer or any active radiotherapy or cytotoxic chemotherapy within the last 6 months of baseline. Participants with a history of basal cell or squamous cell skin cancer may be enrolled at the discretion of the investigator
- •Participants may not be receiving any other investigational agents, or be active participants in any clinical trials. If participants previously participated in a clinical trial, a 30 day washout period for the investigational drug is needed before the participant can be considered for this study
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to linaclotide
- •Uncontrolled current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant or lactating women
- •History of bleeding/coagulation problems. Concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin is acceptable
- •Any medical condition judged by the investigator to constitute a risk to safe participation
- •At risk for obstructing or near-obstructing mechanical gastrointestinal obstruction
- •Chronic use of anti-coagulants or non-NSAID anti-platelet agents will serve as an exclusion only when such medications cannot be safely discontinued before study related endoscopy or surgery
研究组 & 干预措施
Arm I (linaclotide)
Patients receive linaclotide PO daily on days 1-7 and undergo standard of care colonoscopy or surgery on day 7.
干预措施: Linaclotide (Drug)
Arm II (placebo)
Patients receive placebo PO QD on days 1-7 and undergo standard of care colonoscopy or surgery on day 7.
干预措施: Placebo (Other)
结局指标
主要结局
Pharmacodynamics effect on cGMP levels
时间窗: Up to 2 years, plus an additional 12 months for primary analysis
Will compare cGMP levels in adenomas between study arms using a two-sample t-test (alpha=.05; two-sided) or Wilcoxon rank sum test.
次要结局
- Guanylin levels(Up to 2 years)
- Ki-67 expression(Up to 2 years)
- Incidence of adverse events (AEs)(From the time of first dose of linaclotide or placebo until resolution, if related to linaclotide, or through 30 days after occurrence)
- GUCY2C expression(Up to 2 years)
研究者
scott waldman
Associate Professor
Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University