Clinical trial NCT02972541: Neoadjuvant Chemotherapy Verse Surgery Alone After Stent Placement for Obstructive Colonic Cancer
Official title: NeoAdjuvant Chemotherapy Versus Surgery Alone After Stent Placement for Left-sided Obstructive Colonic Cancer:a Multicenter, Controlled, Open-label Clinical Trial (NACSOC Trial)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Colorectal Cancer
Neoadjuvant Chemotherapy
Stent
Obstruction
Lead sponsor: Beijing Chao Yang Hospital
Sponsor class: OTHER
First posted: 2016-11-23
Enrollment: 248
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Disease free survival
timeFrame: From date of randomization until the date of tumor recurrence or death from any cause, assessed up to 5 years
measure: Overall survival
timeFrame: From date of randomization until the date of death from any cause, assessed up to 5 years
measure: Rate of stoma formation
timeFrame: From date of randomization until the follow-up ended, assessed up to 5 years
Secondary outcomes:
measure: Surgical complication
timeFrame: From date of randomization until the first follow-up ended, assessed up to 30 days
measure: Rates of primary colorectal anastomosis
timeFrame: From date of randomization until the first follow-up ended, assessed up to 30 days
measure: R0 resection rate
timeFrame: From date of randomization until the first follow-up ended, assessed up to 30 days
measure: Re-operation rate
timeFrame: From date of randomization until the follow-up ended, assessed up to 5 years
measure: Chemotherapy complete rate
timeFrame: From date of randomization until the chemotherapy ended, assessed up to 1 years
measure: Chemotherapy related complication
timeFrame: From date of randomization until the chemotherapy ended, assessed up to 1 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chaoyang Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Chinese People's Liberation Army General Hospital
state: Beijing
city: Beijing
country: China
facility: Xuanwu Hospital Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Guangzhou
country: China
facility: the Sixth Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
city: Nanjing
country: China
facility: the First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Shijiazhuang
country: China
facility: Fourth Hospital of Hebei Medicial University
state: Hebei
city: Jiamusi
country: China
facility: First Affiliated Hospital of Jiamusi University
state: Heilongjiang
city: Luoyang
country: China
facility: the 150th Central Hospital of Chinese PLA
state: Henan
city: Zhengzhou
country: China
facility: the First Affiliated Hospital of Zhengzhou University
state: Henan
city: Zhengzhou
country: China
facility: the Second Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Wuhan
country: China
facility: Hubei General Hospital
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Changsha
country: China
facility: the Third Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Provincial People'S Hospital
state: Hunan
city: Changchun
country: China
facility: China-Japan Union Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Dalian
country: China
facility: the First Affiliated Hospital of Dalian Medical University
state: Shandong
city: Jinan Shi
country: China
facility: Shandong Provincial Qianfoshan Hospital
state: Shandong
city: Jinan Shi
country: China
facility: Shandong General Hospital
state: Shandong
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Qingdao
country: China
facility: the Affiliated Hospital of Qingdao University
state: Shandong
city: Shanghai
country: China
facility: Changhai Hospital
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Tumor Hospital
state: Shanxi
city: Xi'an
country: China
facility: the First Affiliated Hospital of Xi'An Jiaotong University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: the First Affiliated Hospital of Zhejiang University
state: Zhejiang
city: Jinhua
country: China
facility: Jinhua Hospital of Zhejiang University
state: Zhejiang
city: Wenzhou
country: China
facility: the Second Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: Beijing Chao Yang Hospital
name: zhenjun wang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.