Neoadjuvant Chemotherapy Verse Surgery Alone After Stent Placement for Obstructive Colonic Cancer (NACSOC)

NeoAdjuvant Chemotherapy Versus Surgery Alone After Stent Placement for Left-sided Obstructive Colonic Cancer:a Multicenter, Controlled, Open-label Clinical Trial (NACSOC Trial)

Colorectal cancer is the fourth most common cancer in China. Up to 30% of patients with colorectal cancer present with an emergency obstruction of the large bowel at the time of diagnosis, and 70% of all malignant obstruction occurs in the left-sided colon. Patients with obstruction are associated with worse oncologic outcomes compared with those having nonobstructive tumors. Conventionally, patients with malignant large bowel obstruction receive emergency surgery, with morbidity rates of 30%-60% and mortality rates of 7-22%, and about two-thirds of such patients end up with a permanent stoma.

Self-expanding metallic stents (SEMS) haven been used as a bridge to surgery (to relieve obstruction prior to elective surgery) in patients with potentially resectable colorectal cancer. Several clinical trials demonstrate that SEMS as a bridge to surgery may be superior to emergency surgery considering the short-term outcomes. SEMS is associated with lower morbidity and mortality rate, increased primary anastomosis rate, and decreased stoma creation rate. Although about half of patients can achieve primary anastomosis after stent placement, the primary anastomosis rate is still significantly lower compared with nonobstructing elective surgery. The interval between stent placement and surgery may be not long enough that bowel decompression is insufficient at the time of operation. Furthermore，the long-term oncologic results regarding SEMS as a bridge to surgery are still limited and contradictory. Sabbagh et al. suggest worse overall survival of patients with SEMS insertion compared with emergency surgery, the 5-year cancer-specific mortality was significantly higher in the SEMS group (48% vs 21%, respectively, P=0.02). One interpretation is that tumor cells may disseminate during the procedure of colonic stenting placement. We hypothesis that immediate chemotherapy after stenting may improve overall survival by eradicating micrometastasis. Moreover, neoadjuvant chemotherapy prolongs the interval between stent placement and surgery, and the time for bowel decompression is more sufficient, which may increase the success rate of primary anastomosis and decrease risk of stoma formation.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Obstruction; Neoadjuvant Chemotherapy; Stent
• Intervention / Treatment: Device: Stenting with neoadjuvant chemotherapy; Device: Stenting with immediate Surgery

• Study Type: Interventional
• Enrollment (Anticipated): 248
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: zhenjun wang, MD; Phone Number: 8610-85231604; Email: drzhenjun@163.com
• Study Contact Backup: Name: weigen zeng, MD; Phone Number: 8610-85231604; Email: shen_coco@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100020
      • Recruiting
      • Beijing Chaoyang Hospital, Capital Medical University
    • Beijing, Beijing, China, 100020
      • Recruiting
      • Beijing Friendship Hospital
      • Contact: zhongtao zhang, MD; Phone Number: 8610-63016616; Email: yaohongwei@medmail.com.cn
    • Beijing, Beijing, China, 100020
      • Recruiting
      • Beijing Hospital
      • Contact: gang xiao, MD; Phone Number: 8610-85132266; Email: xgbj@sina.com
    • Beijing, Beijing, China, 100020
      • Recruiting
      • Chinese People's Liberation Army General Hospital
      • Contact: xiaohui du, MD; Email: duxiaohui301@sina.com
    • Beijing, Beijing, China, 100020
      • Recruiting
      • Xuanwu Hospital Capital Medical University
      • Contact: fei li, MD; Email: feili36@ccmu.edu.cn
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences
      • Contact: xi-shan wang, MD; Phone Number: 8610-87787110; Email: 794157254@qq.com
  • Guangdong
    • Guangzhou, Guangdong, China, 510655
      • Recruiting
      • The Sixth Affiliated Hospital of Sun Yat-sen University
      • Contact: lei wang, MD; Phone Number: 8620-38254011; Email: wangl9@mail.sysu.edu.cn
  • Guangxi
    • Nanjing, Guangxi, China, 530021
      • Recruiting
      • The First Affiliated Hospital of Guangxi Medical University
      • Contact: wei-zhong tang, MD; Email: 13978157758@163.com
  • Hebei
    • Shijiazhuang, Hebei, China, 050011
      • Recruiting
      • Fourth Hospital of Hebei Medicial University
      • Contact: guiying wang, MD; Phone Number: 86311-86095588; Email: tizq12@vip.163.com
  • Heilongjiang
    • Jiamusi, Heilongjiang, China, 154003
      • Recruiting
      • First Affiliated Hospital of Jiamusi University
      • Contact: fujun chen, MD; Email: gck8801079@163.com
  • Henan
    • Luoyang, Henan, China, 471031
      • Recruiting
      • the 150th Central Hospital of Chinese PLA
      • Contact: Dong Wei
    • Zhengzhou, Henan, China, 450000
      • Recruiting
      • The First Affiliated Hospital of Zhengzhou University
      • Contact: weitang yuan, MD; Email: 13978157758@163.com
    • Zhengzhou, Henan, China, 450014
      • Recruiting
      • The Second Affiliated Hospital of Zhengzhou University
      • Contact: zhigang pang, MD; Email: pzg63726@sina.com
  • Hubei
    • Wuhan, Hubei, China, 430071
      • Recruiting
      • Zhongnan Hospital of Wuhan University
      • Contact: qun qian, MD; Phone Number: 86-013098824999; Email: qunqian2007@163.com
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Hubei Cancer Hospital
      • Contact: keliang zhang, MD; Phone Number: 8627-87670242; Email: 13071238088@163.com
    • Wuhan, Hubei, China, 430060
      • Recruiting
      • Hubei General Hospital
      • Contact: shilun tong, MD; Email: tongshilun@163.com
  • Hunan
    • Changsha, Hunan, China, 410000
      • Recruiting
      • The Third Xiangya Hospital of Central South University
      • Contact: xiaorong li, MD; Email: lixiaorong@medmail.com
    • Changsha, Hunan, China, 410005
      • Recruiting
      • Hunan Provincial People's Hospital
      • Contact: zhongcheng huang, MD; Phone Number: 86731-83929555; Email: huangzc369@163.com
  • Jilin
    • Changchun, Jilin, China, 130033
      • Recruiting
      • China-Japan Union Hospital of Jilin University
      • Contact: tongjun liu, MD; Email: tongjunliu@163.com
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Recruiting
      • Shengjing Hospital of China Medical University
      • Contact: yong feng, MD; Email: fengy@sj-hospital.org
  • Shandong
    • Dalian, Shandong, China, 116011
      • Recruiting
      • The First Affiliated Hospital Of Dalian Medical University
    • Jinan, Shandong, China, 250022
      • Recruiting
      • Qilu Hospital of Shandong University
      • Contact: Yong Dai, M.D.; Email: 18560085128@163.com
    • Jinan Shi, Shandong, China, 250014
      • Recruiting
      • ShanDong Provincial QianFoShan Hospital
      • Contact: lijian xia, MD; Email: xiaalbert2758@163.com
    • Jinan Shi, Shandong, China, 250021
      • Recruiting
      • Shandong General Hospital
      • Contact: changqing jing, MD; Email: jing66510122@sina.com
    • Qingdao, Shandong, China, 266000
      • Recruiting
      • The Affiliated Hospital of Qingdao University
      • Contact: yun lu, MD; Email: cloudylucn@126.com
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Changhai Hospital
      • Contact: chuangang fu, MD; Email: fugang416@126.com
  • Shanxi
    • Taiyuan, Shanxi, China, 030013
      • Recruiting
      • Shanxi Tumor Hospital
      • Contact: xiaobo liang, MD; Phone Number: 860351-4651714; Email: liangxiaobo@medmail.com.cn
    • Xi'an, Shanxi, China, 710061
      • Recruiting
      • The First Affiliated Hospital of Xi'an Jiaotong University
      • Contact: xiangming che, MD; Email: chexiang@mail.xjtu.edu.cn
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital Sichuan University
      • Contact: zi-qiang wang, MD; Email: wangzqzyh@163.com
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Affiliated Hospital of Zhejiang University
      • Contact: jianjiang lin, MD; Email: ljjzju@163.com
    • Jinhua, Zhejiang, China, 321000
      • Recruiting
      • Jinhua Hospital of Zhejiang University
      • Contact: jinlin du, MD; Email: djl9090@163.com
    • Wenzhou, Zhejiang, China, 325027
      • Recruiting
      • The Second Affiliated Hospital of Wenzhou Medical University
      • Contact: changbao liu, MD; Email: lcb@wzhealth.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Radiologically proven colonic obstruction of the left colon/upper rectum presumed secondary to a carcinoma
• Able to give written, informed consent
• Primary tumor was resectable
• ECOG score 0 or 1
• Haemoglobin greater than 100 g/L after transfusion before chemotherapy,
• White blood cells greater than 3.0×10⁹ /L
• Platelets greater than 100×10⁹ / L;
• Glomerular filtration rate greater than 50 mL per minute as calculated by the Wright or Cockroft formula
• Bilirubin less than 1.5×Upper Limit of Normal(ULN)
• ALT and AST less than 2.5×ULN

Exclusion Criteria:

• Distal rectal cancers(equal or less than 10cm from the anal verge)
• Patients with signs of peritonitis and/or bowel perforation
• Patients who did not give informed consent
• Patients who were considered unfit for operative treatment or refuse surgery.
• Patients with suspected or proven metastatic adenocarcinoma;
• Patients with unresectable colorectal cancer, or planning for palliative treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Stenting with neoadjuvant chemotherapy; After clinical success of colonic stenting, patients will receive neoadjuvant chemotherapy with mFOLFOX6 regimen for 3 cycles or CapeOx regimen for 2 cycles. Patients will undergo surgery 3-5 weeks after the last cycle of chemotherapy, type and extent of the surgery will be selected by the surgeon.	Device: Stenting with neoadjuvant chemotherapy; After clinical success of colonic stenting, patients will be given neoadjuvant chemotherapy. Surgery is performed after 3 cycles of mFOLFOX6 or 2 cycles of CapeOx. The choice of surgery performed is up to the individual consultant colorectal surgeon. Patients will receive 5-9 cycles of mFOLFOX6 or 4-6 cycles of CapeoX after surgery. Each cycle of mFOLFOX6 consists of racemic leucovorin 400 mg/m², oxaliplatin 85 mg/m² in a 2-h infusion, bolus fluorouracil 400 mg/m² on day 1, and a 46-h infusion of fluorouracil 2400 mg/m². Each cycle of CapeOx consists of oxaliplatin 130 mg/m2, capecitabine 100 mg/m2 twice daily for 14 days.
ACTIVE_COMPARATOR: Stenting with Immediate Surgery; After clinical success of colonic stenting, patients will undergo surgery 7-14 days after inclusion. Type and extent of the elective surgery will be selected by the surgeon.	Device: Stenting with immediate Surgery; After clinical success of colonic stenting, patients will undergo surgery 7-14 days later. The choice of surgery performed is up to the individual consultant colorectal surgeon. Patients will receive 8-12 cycles of mFOLFOX6 or 6-8 cycles of CapeoX after surgery. Each cycle of mFOLFOX6 consists of racemic leucovorin 400 mg/m², oxaliplatin 85 mg/m² in a 2-h infusion, bolus fluorouracil 400 mg/m² on day 1, and a 46-h infusion of fluorouracil 2400 mg/m². Each cycle of CapeOx consists of oxaliplatin 130 mg/m2, capecitabine 100 mg/m2 twice daily for 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease free survival	From date of randomization until the date of tumor recurrence or death from any cause, assessed up to 5 years
Overall survival	From date of randomization until the date of death from any cause, assessed up to 5 years
Rate of stoma formation	From date of randomization until the follow-up ended, assessed up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgical complication	Including but not limited to: anastomotic leakage, wound infection, intra-abdominal sepsis,perioperative mortality, etc.	From date of randomization until the first follow-up ended, assessed up to 30 days
Rates of primary colorectal anastomosis	The primary colorectal anastomosis was defined as: the patients received one-stage surgery and colorectal anastomosis.	From date of randomization until the first follow-up ended, assessed up to 30 days
R0 resection rate	R0 resection is defined as negative resection margins and no residual tumor.	From date of randomization until the first follow-up ended, assessed up to 30 days
Re-operation rate		From date of randomization until the follow-up ended, assessed up to 5 years
Chemotherapy complete rate		From date of randomization until the chemotherapy ended, assessed up to 1 years
Chemotherapy related complication		From date of randomization until the chemotherapy ended, assessed up to 1 years

Collaborators and Investigators

• Sponsor: Beijing Chao Yang Hospital
• Investigators: Principal Investigator: zhenjun wang, MD, Beijing Chao Yang Hospital

Publications and helpful links

General Publications

• Sabbagh C, Browet F, Diouf M, Cosse C, Brehant O, Bartoli E, Mauvais F, Chauffert B, Dupas JL, Nguyen-Khac E, Regimbeau JM. Is stenting as "a bridge to surgery" an oncologically safe strategy for the management of acute, left-sided, malignant, colonic obstruction? A comparative study with a propensity score analysis. Ann Surg. 2013 Jul;258(1):107-15. doi: 10.1097/SLA.0b013e31827e30ce.
• van Hooft JE, Bemelman WA, Oldenburg B, Marinelli AW, Lutke Holzik MF, Grubben MJ, Sprangers MA, Dijkgraaf MG, Fockens P; collaborative Dutch Stent-In study group. Colonic stenting versus emergency surgery for acute left-sided malignant colonic obstruction: a multicentre randomised trial. Lancet Oncol. 2011 Apr;12(4):344-52. doi: 10.1016/S1470-2045(11)70035-3. Erratum In: Lancet Oncol. 2011 May;12(5):418.
• Young CJ, De-Loyde KJ, Young JM, Solomon MJ, Chew EH, Byrne CM, Salkeld G, Faragher IG. Improving Quality of Life for People with Incurable Large-Bowel Obstruction: Randomized Control Trial of Colonic Stent Insertion. Dis Colon Rectum. 2015 Sep;58(9):838-49. doi: 10.1097/DCR.0000000000000431.
• Huang X, Lv B, Zhang S, Meng L. Preoperative colonic stents versus emergency surgery for acute left-sided malignant colonic obstruction: a meta-analysis. J Gastrointest Surg. 2014 Mar;18(3):584-91. doi: 10.1007/s11605-013-2344-9. Epub 2013 Oct 30.
• Ohman U. Prognosis in patients with obstructing colorectal carcinoma. Am J Surg. 1982 Jun;143(6):742-7. doi: 10.1016/0002-9610(82)90050-2.
• Kim JS, Hur H, Min BS, Sohn SK, Cho CH, Kim NK. Oncologic outcomes of self-expanding metallic stent insertion as a bridge to surgery in the management of left-sided colon cancer obstruction: comparison with nonobstructing elective surgery. World J Surg. 2009 Jun;33(6):1281-6. doi: 10.1007/s00268-009-0007-5.
• Han J, Wang Z, Dai Y, Li X, Qian Q, Wang G, Wei G, Zeng W, Ma L, Zhao B, Wang Y, Yang K, Ding Z, Hu X. [Preliminary report on prospective, multicenter, open research of selective surgery after expandable stent combined with neoadjuvant chemotherapy in the treatment of obstructive left hemicolon cancer]. Zhonghua Wei Chang Wai Ke Za Zhi. 2018 Nov 25;21(11):1233-1239. Chinese.

Study record dates

Study Major Dates

• Study Start: September 30, 2016
• Primary Completion (ANTICIPATED): December 30, 2023
• Study Completion (ANTICIPATED): December 30, 2023

Study Registration Dates

• First Submitted: September 8, 2016
• First Submitted That Met QC Criteria: November 21, 2016
• First Posted (ESTIMATE): November 23, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2021
• Last Update Submitted That Met QC Criteria: February 4, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: 2016-161-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO