A Double Blind Placebo-Controlled Trial of Eflornithine and Sulindac to Prevent Recurrence of High Risk Adenomas and Second Primary Colorectal Cancers in Patients With Stage 0-III Colon or Rectal Cancer, Phase III - Preventing Adenomas of the Colon With Eflornithine and Sulindac (PACES)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 354
- 试验地点
- 983
- 主要终点
- Event rate, defined as rate of high-risk adenoma or second primary colorectal cancer (CRC)
研究概览
简要总结
The investigators hypothesize that the combination of eflornithine and sulindac will be effective in reducing a three-year event rate of adenomas and second primary colorectal cancers in patients previously treated for Stages 0 through III colon or rectal cancer.
详细描述
The purpose of this study is to assess whether the combination of eflornithine 500 mg and sulindac 150 mg (compared to corresponding placebos) has efficacy against colorectal lesions with respect to high-grade dysplasia, adenomas with villous features, adenomas 1 cm or greater, multiple adenomas, any adenomas >/= 0.3 cm, total advanced colorectal events, or total colorectal events.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
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
- •History of Stage 0-III colon or rectal cancer with primary resection 1 year previously
- •Post-operative colonoscopy and CT scans of chest, abdomen & pelvis showing no evidence of disease
- •Must not have cardiovascular risk factors including unstable angina, history of myocardial infarction, or cerebrovascular accident, coronary artery bypass surgery, or NY Heart Assoc Class III or IV heart failure.
- •Patients must not have known uncontrolled hyperlipidemia (defined as LDL-C >/= 190 mg/dL or triglycerides >/= 500 mg/dL within the past 3 years or uncontrolled high blood pressure (systolic blood pressure > 150 mm Hg) within 28 days prior to registration
- •At least 30 days from completion of adjuvant chemo and RT.
- •Presence of gastroesophageal reflux disease acceptable if controlled with medications
- •Not receiving or planning to receive concomitant intravenous corticosteroids on a regular basis,nonsteroidal anti-inflammatory drugs (NSAIDs), nor anticoagulants on a regular predictable intermittent basis. NSAID use must not exceed 10 days per month; Maximum aspirin dose
- •100 mg per day or ≤ two 325 mg tablets per week. Inhaled steroids (i.e. for asthma or related conditions) are allowed.
- •Able to swallow oral medications
- •Laboratory: WBC ≥ 4.0 x 1000/mcL, platelets ≥ 100,000/mcL and hemoglobin > 11.0 g/dL. (A total WBC ≥ 3.1 x 1000/mcL is allowed for non-Hispanic black males and total WBC ≥ 3.4 x 1000/mcL for non-Hispanic black females. Serum bilirubin ≤ 2.0 mg/dL and AST (SGOT) or ALT(SGPT) ≤ 2 x IULN. Serum creatinine ≤ 1.5 x IULN
- •Zubrod PS 0-1, 18 years of age or older
- •Will not participate in any other clinical trial for the treatment or prevention of cancer unless off protocol treatment, on follow-up phase only
- •Offered opportunity to participate in blood specimen banking
排除标准
- •History of colon resection > 40 cm
- •Mid-low rectal cancer
- •Recurrent or metastatic disease
- •High cardiovascular risk; Uncontrolled hypertension
- •Planned radiation therapy or additional chemotherapy
- •Documented history of gastric/duodenal ulcer within last 12 months and/or current treatment or active symptoms of gastric/duodenal ulcer
- •Known history of familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, or inflammatory bowel disease
- •≥ 30 dB uncorrectable hearing loss for age of any of the five tested frequencies on prestudy audiogram
- •Known hypersensitivity to sulindac or excipient byproducts. Previous asthma, urticaria, or allergic-type reaction to aspirin or other NSAIDs
- •Significant medical or psychiatric condition that would preclude study completion (8 years)
- •No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for > 5 years
- •Pregnant or nursing women. Women/men of reproductive potential must agree to use effective contraception
研究组 & 干预措施
eflornithine placebo & sulindac placebo
Eflornithine placebo 2 tablets, PO, daily for 3 years. Sulindac placebo, 1 tablet, PO, daily for 3 years.
干预措施: Eflornithine placebo & sulindac placebo (Drug)
Eflornithine & sulindac placebo
Eflornithine two 250 mg tablets PO daily for 3 years. Sulindac placebo one tablet PO daily for 3 years.
干预措施: eflornithine & sulindac placebo (Drug)
Eflornithine placebo & sulindac
Eflornithine placebo 2 tablets PO daily for 3 years. Sulindac one 150 mg tablet PO daily for 3 years.
干预措施: Eflornithine placebo & sulindac (Drug)
Eflornithine plus sulindac
Eflornithine two 250 mg tablets PO daily for 3 years. Sulindac one 150 mg tablet PO daily for 3 years.
干预措施: Eflornithine plus sulindac (Drug)
结局指标
主要结局
Event rate, defined as rate of high-risk adenoma or second primary colorectal cancer (CRC)
时间窗: 3 years after registration
High risk adenoma is defined as either advanced adenoma (villous or tubulovillous histology, size \>= 1 cm, or high grade dysplasia) or multiple adenomas (3 or more each \> 0.3 cm). The primary analysis of the 3-year event rate will be performed using logistic regression, testing the main effect of treatment and adjusting for the baseline stratification factor. A two-arm binomial design without continuity correction will be used.
次要结局
- Total colorectal event rate, defined as the number of patients with at least one colorectal event (advanced colorectal event or adenoma > 0.3 cm)(Up to 8 years)
- Total advanced colorectal event rate, defined as the number of patients with at least one high risk adenoma, second primary CRC, CRC recurrence, or metastasis(Up to 8 years)
- Colon cancer recurrence(Up to 8 years)
- High-grade dysplasia(Up to 8 years)
- Adenomas >= 1 cm(Up to 8 years)
- The number of patients with development of any adenoma > 0.3 cm(Up to 8 years)
- Adenomas with villous features, defined as villous histology (villous and tubulovillous adenomas)(Up to 8 years)
- Multiple adenomas, defined as 3 or more adenomas all measuring > 0.3 cm(Up to 8 years)
- Time to first clinically apparent high-risk adenoma or second primary CRC(From date of registration to date at which high-risk adenoma or second primary CRC is detected, up to 8 years)
- Toxicity(Up to 3 years)
- Baseline statin use(Up to 3 years)
- Baseline meat consumption(Up to 3 years)
- PK analysis(Up to 3 years)
- Biomarker identification based on Integrated Comprehensive Droplet Digital Detection technology(Up to 3 years (though the timing of this isn't clear to me))
- Cancer type (colorectal vs rectal)(Up to 3 years)