Randomized Phase II Trial of Aspirin and Difluoromethylornithine (DFMO) in Patients at High Risk of Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 107
- 试验地点
- 3
- 主要终点
- Adenoma Recurrence Rate for the Treatment Arm Relative to Placebo
研究概览
简要总结
This phase II trial is studying how well giving acetylsalicylic acid together with eflornithine works in treating patients at high risk for colorectal cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of acetylsalicylic acid and eflornithine may prevent colorectal cancer.
详细描述
PRIMARY OBJECTIVES:
I. The proportion of subjects with an adenoma recurrence at the 1-year follow-up colonoscopy exam. This adenoma recurrence rate for difluoromethylornithine (DFMO) (eflornithine) + aspirin will be compared to double placebo to see if there is improvement in the adenoma recurrence rate in this patient population.
SECONDARY OBJECTIVES:
I. To determine the relative tolerability and safety of the treatment regimens administered for 12 months.
II. To determine the effect of the study drugs (aspirin [acetylsalicylic acid] + DFMO) and placebo with respect to proliferation (Ki67 labeling index), apoptosis (caspase-3 expression assay), and drug effect markers (COX-1, -2, polyamines, PGE2) from adenomas, aberrant crypt focus (ACF) and normal-appearing mucosa using pre- and 12-month post-intervention tissue biopsy samples.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Current or prior advanced adenomas
- •Advanced adenomas are defined as subject with polyps >= 1 cm, tubulovillous adenomas (25-75 percent villous features), villous adenomas (> 75 percent villous), or high-grade dysplasia
- •Prior colon cancer (>= 3 years out from invasive cancer)
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- •Ability to under and the willingness to sign a written informed consent document
- •Willingness to provide mandatory tissue for research purposes
- •Negative pregnancy test =< 7 days prior to randomization
- •Hemoglobin (Hgb) within normal limits for institution/lab
- •Platelet count >= 100,000/ul
- •White blood cell count (WBC) >= 3,000/ul
- •Alanine aminotransferase (ALT) =< 2 x institutional upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) =< 2 x institutional ULN
- •Total bilirubin =< 1.5 x institutional ULN
- •Serum calcium =< institutional ULN
- •Serum creatinine =< 1.5 x institutional ULN
- •Colonoscopy =< 45 days prior to randomization with removal of all adenomas or polyps >= 2 mm in size
排除标准
- •Any history of current or prior rectal cancer
- •Known diagnosis of colon heritable cancer syndrome (familial adenomatous polyposis [FAP], hereditary nonpolyposis colorectal cancer [HNPCC]) or inflammatory bowel disease (Crohn's disease, ulcerative colitis)
- •Inability to swallow pills
- •Bleeding diathesis
- •New diagnosis of carcinoma
- •History of hypersensitivity to COX-2 inhibitors, sulfonamides, nonsteroidal antiinflammatory drugs (NSAIDs), salicylates, or ursodeoxycholic acid
- •History of gastroduodenal ulcers documented =< 1 year
- •Known inability to participate in the scheduled follow-up tests
- •Significant medical or psychiatric problems which would make the subject a poor protocol candidate, in the opinion of the treating physician
- •Total colectomy
- •Patients with a colostomy
- •History of pelvic or rectal radiation therapy
- •History of invasive carcinoma =< 5 years (except subjects with Dukes A/B1 carcinoma =< 5 years prior to pre-registration or any stage of colon cancer if >= 3 years post surgical resection)
- •Acute liver disease, unexplained transaminase elevations, or elevated serum calcium
- •History of allergic reactions attributed to compounds of similar chemical composition to the study agents
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
- •Concomitant corticosteroids or anticoagulants needed on a regular or predictable intermittent basis
- •New diagnosis of invasive carcinoma
- •Use of non-study investigational agent(s) =< 3 months prior to randomization
- •Chemotherapy =< 6 months prior to randomization (Note: topical chemotherapy will be assessed on a case-by-case basis)
- •Pregnant women
- •Nursing women
- •Men or women of childbearing potential who are unwilling to employ adequate contraception
- •Regular use of NSAIDs =< 6 weeks prior to randomization, defined as a frequency of 7 consecutive days (1 week) for > 3 weeks (Exception: low dose aspirin [81 mg] for those subjects who are chronic users of aspirin prior to the beginning of the study)
研究组 & 干预措施
Arm I (acetylsalicylic acid and eflornithine)
Patients receive acetylsalicylic acid PO once daily and eflornithine PO twice daily on days 1-28.
干预措施: Aspirin (Drug)
Arm I (acetylsalicylic acid and eflornithine)
Patients receive acetylsalicylic acid PO once daily and eflornithine PO twice daily on days 1-28.
干预措施: Eflornithine (Drug)
Arm I (acetylsalicylic acid and eflornithine)
Patients receive acetylsalicylic acid PO once daily and eflornithine PO twice daily on days 1-28.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (acetylsalicylic acid and eflornithine)
Patients receive acetylsalicylic acid PO once daily and eflornithine PO twice daily on days 1-28.
干预措施: Telephone-Based Intervention (Other)
Arm II (placebo)
Patients receive placebo PO three times daily on days 1-28.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (placebo)
Patients receive placebo PO three times daily on days 1-28.
干预措施: Placebo (Other)
Arm II (placebo)
Patients receive placebo PO three times daily on days 1-28.
干预措施: Telephone-Based Intervention (Other)
结局指标
主要结局
Adenoma Recurrence Rate for the Treatment Arm Relative to Placebo
时间窗: At 1 year
The primary endpoint is the proportion of participants with an adenoma recurrence at the 1-year follow-up colonoscopy exam. All eligible, randomized participants who have signed a consent form and received at least one follow-up endoscopy exam will be considered evaluable for the primary endpoint. This adenoma recurrence rate for DFMO + aspirin will be compared to double placebo to see if there is improvement in the adenoma recurrence rate in this patient population. A 1-sided Chi-square test was used to determine if there was a significant difference between treatment arms.
次要结局
- Characterization of ACF(Baseline)
- Safety, Tolerability, and Adverse Events of Study Treatment(Up to 48 months from beginning treatment.)
- Comparison of the Percent Change in ACF Number Across the 2 Treatment Arms(At baseline and 12 months)
- ACF Characteristics vs Adenoma Recurrence Rate(At baseline and 1 year)