A Randomized Double Blinded Study of Curcumin With Pre-operative Capecitabine and Radiation Therapy Followed by Surgery for Rectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Number of Participants With Pathologic Complete Response (pCR) Rate
研究概览
简要总结
This randomized phase II trial studies how well radiation therapy and capecitabine with or without curcumin before surgery works in treating patients with rectal cancer. Drugs such as curcumin may make tumor cells more sensitive to radiation therapy. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether chemotherapy and radiation therapy is more effective with or without curcumin when given before surgery in patients with rectal cancer.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the efficacy of a combination of capecitabine and radiation therapy with or without curcumin in locally advanced rectal cancer as assessed by pathological complete response rate.
SECONDARY OBJECTIVES:
I. To determine downstaging, local control, disease-free survival and overall survival rates.
II. To determine serum and rectal tumor tissue pharmacology of curcumin and its metabolites in the above patients and its correlation with clinical response.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients must have clinical stage T3,4 N0,1,2 or T2N1,2 adenocarcinoma of the rectum; patients will be clinically staged using endorectal ultrasound, pelvic computed tomography (CT) or magnetic resonance imaging (MRI), and physical examination
- •Histology must be confirmed with review by the Department of Pathology at MD Anderson Cancer Center (MDACC)
- •All patients must have no distant metastatic disease in the liver, peritoneum, lungs, or paraaortic lymph nodes
- •Patients must have a performance status (Karnofsky scale) of 70% or greater
- •Absolute neutrophil count (ANC) > 1200 cells/mm^3
- •Platelets > 100,000/mm^3
- •Total serum bilirubin < 2 mg/dl
- •Blood urea nitrogen (BUN) < 30 mg/dl
- •Creatinine < 1.5 mg/dl or creatinine clearance > 50cc/min (estimated as calculated with Cockcroft-Gault equation)
- •Patients must have signed informed consent indicating that they are aware of the investigational nature of the study, and are aware that participation is voluntary; patients must also agree to refrain from use of additional herbal supplements during the course of the study
- •Patients will agree to continue contraception for 30 days from the date of the last study drug administration; sexually active males must practice contraception during the study
- •Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential
排除标准
- •Prior complete course up to 5 Gy of radiotherapy to the pelvis
- •Pregnant or lactating woman; women of childbearing potential who have not undergone a hysterectomy with either a positive or no pregnancy test at baseline; women / men of childbearing potential not using a reliable and appropriate contraceptive method (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner)
- •Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer
- •Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or requiring IV antibiotics, cardiac disease New York Heart Association (NYHA) class III or IV, unstable angina pectoris, unstable cardiac arrhythmia or tachycardia (heart rate > 100 beats/minute), or psychiatric illness/ social situations that would limit compliance with the study requirements are excluded
- •Other serious uncontrolled medical conditions that the investigator feels might compromise study participation
- •Major surgery within 4 weeks of the start of study treatment
- •Prior unanticipated severe reaction to fluoropyrimidine therapy or known hypersensitivity to 5-fluorouracil or capecitabine or curcumin
- •Concurrent use of Coumadin other than low dose (1 mg) Coumadin used for line patency; patients on Coumadin must be changed to Lovenox at least 1 week prior to starting capecitabine
- •Concurrent use of cimetidine, allopurinol, or aluminium hydroxide and magnesium hydroxide-containing antacids such as Maalox
- •Sorivudine and brivudine use within 4 weeks of the start of study treatment
研究组 & 干预措施
Arm I (curcumin)
Patients undergo radiation therapy 5 days a week for a total of 28 fractions. Patients also receive capecitabine PO BID on the days of radiation therapy and curcumin PO BID in weeks 1-11.5.
干预措施: Capecitabine (Drug)
Arm I (curcumin)
Patients undergo radiation therapy 5 days a week for a total of 28 fractions. Patients also receive capecitabine PO BID on the days of radiation therapy and curcumin PO BID in weeks 1-11.5.
干预措施: Curcumin (Dietary Supplement)
Arm I (curcumin)
Patients undergo radiation therapy 5 days a week for a total of 28 fractions. Patients also receive capecitabine PO BID on the days of radiation therapy and curcumin PO BID in weeks 1-11.5.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (curcumin)
Patients undergo radiation therapy 5 days a week for a total of 28 fractions. Patients also receive capecitabine PO BID on the days of radiation therapy and curcumin PO BID in weeks 1-11.5.
干预措施: Pharmacological Study (Other)
Arm I (curcumin)
Patients undergo radiation therapy 5 days a week for a total of 28 fractions. Patients also receive capecitabine PO BID on the days of radiation therapy and curcumin PO BID in weeks 1-11.5.
干预措施: Quality-of-Life Assessment (Other)
Arm I (curcumin)
Patients undergo radiation therapy 5 days a week for a total of 28 fractions. Patients also receive capecitabine PO BID on the days of radiation therapy and curcumin PO BID in weeks 1-11.5.
干预措施: Radiation Therapy (Radiation)
Arm II (placebo)
Patients undergo radiation therapy and receive capecitabine as in Arm I. Patients also receive placebo PO BID in weeks 1-11.5.
干预措施: Capecitabine (Drug)
Arm II (placebo)
Patients undergo radiation therapy and receive capecitabine as in Arm I. Patients also receive placebo PO BID in weeks 1-11.5.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (placebo)
Patients undergo radiation therapy and receive capecitabine as in Arm I. Patients also receive placebo PO BID in weeks 1-11.5.
干预措施: Pharmacological Study (Other)
Arm II (placebo)
Patients undergo radiation therapy and receive capecitabine as in Arm I. Patients also receive placebo PO BID in weeks 1-11.5.
干预措施: Placebo (Other)
Arm II (placebo)
Patients undergo radiation therapy and receive capecitabine as in Arm I. Patients also receive placebo PO BID in weeks 1-11.5.
干预措施: Quality-of-Life Assessment (Other)
Arm II (placebo)
Patients undergo radiation therapy and receive capecitabine as in Arm I. Patients also receive placebo PO BID in weeks 1-11.5.
干预措施: Radiation Therapy (Radiation)
结局指标
主要结局
Number of Participants With Pathologic Complete Response (pCR) Rate
时间窗: At time of surgery
Compared the rate of pCR between treatment arms with Fisher's exact test.
次要结局
- Change in Curcumin Level in Tumor Tissue(Baseline to 11.5 weeks)
- Change in Curcumin Level in Serum(assessed 1 hr pre/post curcumin administration on one of the days during week 2 of radiation therapy (fractions 6-10))
- Tumor Regression Grade(Baseline to 11.5 weeks)
- Overall Survival (OS)(5 years)
- Progression Free Survival (PFS)(5 years)
- Number of Participants With Tumor Downstaging(Baseline to 11.5 weeks)