A Phase II Trial of Preoperative Capecitabine Plus Irinotecan Followed by Combined Modality Capecitabine and Radiation for Locally Advanced Rectal Cancer: Hoosier Oncology Group GI03-53
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 22
- 试验地点
- 9
- 主要终点
- Pathological Complete Response (pCR) Rate
研究概览
简要总结
Preoperative induction chemotherapy has been successfully used in a variety of malignancies and provides several advantages over postoperative therapy. Combination of 5-FU/Leucovorin/CPT-11 has demonstrated significantly better response rate than 5-FU/Leucovorin alone. Replacing 5-FU with oral capecitabine in combination with CPT-11 has emerged as a potentially more effective, safe and convenient treatment option for metastatic colorectal cancer. Capecitabine is also well tolerated in concurrent treatment with radiation. Recent data has shown that preoperative radiation appears to be significantly more effective in increasing resectability rates.
This trial will investigate the activity of capecitabine and CPT-11 combination in the preoperative setting followed by chemoradiation with capecitabine in locally advanced rectal cancer to improve response and decrease local recurrence. We will also study whether TS, TP, DPD and carboxyesterase expressions correlate with the objective response rate with this chemotherapy and chemoradiation regimen.
详细描述
OUTLINE: This is a multi-center study.
Biopsy per EUS
- Irinotecan 200 mg/m2 IV, day 1
- Capecitabine 1000* mg/m2 PO BID day 1-14 Repeat every three weeks for two cycles* For calculated creatinine clearance of 30-50 mL/min or patients > 70years old, capecitabine starting dose is 825 mg/m2 PO BID
Beginning at week 7 or following recovery from chemotherapy:
- Pelvic XRT 45 Gy/1.8 Gy/fx/qd+5.4 Gy/1.8 Gy/fx/qd for T3+9 Gy/1.8 Gy/fx/qd for T4
- Capecitabine 825* mg/m2 PO BID, 5 days/week, throughout XRT* For calculated creatinine clearance of 30-50 mL/min or patients > 70years old, capecitabine starting dose is 650 mg/m2 PO BID
- Surgery within 8weeks following chemoradiotherapy
- Adjuvant Chemotherapy at investigator's discretion
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
- •Histologically confirmed adenocarcinoma of the rectum < 15 cm from the anal verge without evidence of distant metastasis·
- •Measurable disease. ·
- •Either mobile cancers (with clinical stage T3 or T4 by endorectal ultrasound) or fixed cancer (defined as clinical T4 for this study) on palpation. ·
- •Malignant disease may not extend to the anal canal (across the dentate line)
排除标准
- •No prior chemotherapy or radiation therapy to the pelvis.
- •Patients with clinical stage T 1-2, N0 rectal cancer who are candidates for primary resection are not eligible·
- •No synchronous colonic cancer unless the synchronous tumor is Tis or T1 and has been completely resected·
- •Patients must not be taking warfarin·
- •No prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-Fluorouracil or known DPD deficiency.·
- •No known existing uncontrolled coagulopathy·
- •Negative pregnancy test·
- •No current breastfeeding·
- •No serious concomitant systemic disorders incompatible with the study· No prior malignancies with the exception of curatively treated basal or squamous carcinoma of the skin, carcinoma in-situ of the cervix, or any other cancer for which the patient has been disease-free for < 5 years.·
- •Patients must not be treated with any of the following while on protocol therapy or within 28 days prior to beginning protocol therapy: sorivudine, brivudine, cimetidine, allopurinol.
- •Patients on dilantin must have regular monitoring of dilantin levels.
研究组 & 干预措施
Investigational Treatment
-
Irinotecan 200 mg/m2 IV, day 1
-
Capecitabine 1000* mg/m2 po bid day 1-14; repeat every three weeks for two cycles
-
For calculated creatinine clearance of 30-50 mL/min or patients > 70 years old, capecitabine starting dose is 825 mg/m2 po bid
-
EUS
-
Neoadjuvant Chemotherapy
-
Preoperative Radiation
-
Surgery
-
Adjuvant Chemotherapy (at discretion of treating physician)
干预措施: Capecitabine (Drug)
Investigational Treatment
-
Irinotecan 200 mg/m2 IV, day 1
-
Capecitabine 1000* mg/m2 po bid day 1-14; repeat every three weeks for two cycles
-
For calculated creatinine clearance of 30-50 mL/min or patients > 70 years old, capecitabine starting dose is 825 mg/m2 po bid
-
EUS
-
Neoadjuvant Chemotherapy
-
Preoperative Radiation
-
Surgery
-
Adjuvant Chemotherapy (at discretion of treating physician)
干预措施: Irinotecan (Drug)
Investigational Treatment
-
Irinotecan 200 mg/m2 IV, day 1
-
Capecitabine 1000* mg/m2 po bid day 1-14; repeat every three weeks for two cycles
-
For calculated creatinine clearance of 30-50 mL/min or patients > 70 years old, capecitabine starting dose is 825 mg/m2 po bid
-
EUS
-
Neoadjuvant Chemotherapy
-
Preoperative Radiation
-
Surgery
-
Adjuvant Chemotherapy (at discretion of treating physician)
干预措施: EUS (Procedure)
Investigational Treatment
-
Irinotecan 200 mg/m2 IV, day 1
-
Capecitabine 1000* mg/m2 po bid day 1-14; repeat every three weeks for two cycles
-
For calculated creatinine clearance of 30-50 mL/min or patients > 70 years old, capecitabine starting dose is 825 mg/m2 po bid
-
EUS
-
Neoadjuvant Chemotherapy
-
Preoperative Radiation
-
Surgery
-
Adjuvant Chemotherapy (at discretion of treating physician)
干预措施: Neoadjuvant Chemotherapy (Drug)
Investigational Treatment
-
Irinotecan 200 mg/m2 IV, day 1
-
Capecitabine 1000* mg/m2 po bid day 1-14; repeat every three weeks for two cycles
-
For calculated creatinine clearance of 30-50 mL/min or patients > 70 years old, capecitabine starting dose is 825 mg/m2 po bid
-
EUS
-
Neoadjuvant Chemotherapy
-
Preoperative Radiation
-
Surgery
-
Adjuvant Chemotherapy (at discretion of treating physician)
干预措施: Preoperative Radiation (Procedure)
Investigational Treatment
-
Irinotecan 200 mg/m2 IV, day 1
-
Capecitabine 1000* mg/m2 po bid day 1-14; repeat every three weeks for two cycles
-
For calculated creatinine clearance of 30-50 mL/min or patients > 70 years old, capecitabine starting dose is 825 mg/m2 po bid
-
EUS
-
Neoadjuvant Chemotherapy
-
Preoperative Radiation
-
Surgery
-
Adjuvant Chemotherapy (at discretion of treating physician)
干预措施: Surgery (Procedure)
Investigational Treatment
-
Irinotecan 200 mg/m2 IV, day 1
-
Capecitabine 1000* mg/m2 po bid day 1-14; repeat every three weeks for two cycles
-
For calculated creatinine clearance of 30-50 mL/min or patients > 70 years old, capecitabine starting dose is 825 mg/m2 po bid
-
EUS
-
Neoadjuvant Chemotherapy
-
Preoperative Radiation
-
Surgery
-
Adjuvant Chemotherapy (at discretion of treating physician)
干预措施: Adjuvant Chemotherapy (Procedure)
结局指标
主要结局
Pathological Complete Response (pCR) Rate
时间窗: 36 months
· To determine the pathological response rate of preoperative chemotherapy with capecitabine and irinotecan followed by combined modality chemoradiation with capecitabine in patients with locally advanced rectal cancer. Pathological response was defined in the protocol as the proportion of complete (pCR) and non-complete pathological response (pNCR) among all evaluable patients.
次要结局
- Local and Distant Disease Recurrence Rates(36 months)
- Rate of Clinical Response(36 months)
- Disease-Free Survival(36 months)
研究者
Gabi Chiorean, MD
Sponsor-Investigator
Hoosier Cancer Research Network