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

Colorectal Cancer Clinical Trial

— NACSOC  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02972541
• Other study ID #: 2016-161-1
• Status: Recruiting
• Phase: N/A
• Start date: September 30, 2016
• Est. completion date: December 30, 2023

Study information

• Verified date: February 2021
• Source: Beijing Chao Yang Hospital
• Contact: zhenjun wang, MD
• Phone: 8610-85231604
• Email: drzhenjun[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 248
• Est. completion date: December 30, 2023
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 3.0×10? /L
• Platelets greater than 100×10? / 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.

Related Conditions & MeSH terms

• Colonic Neoplasms
• Colorectal Cancer
• Neoadjuvant Chemotherapy
• Obstruction
• Stent

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Beijing Chaoyang Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Friendship Hospital	Beijing	Beijing
China	Beijing Hospital	Beijing	Beijing
China	Chinese People's Liberation Army General Hospital	Beijing	Beijing
China	Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing
China	Xuanwu Hospital Capital Medical University	Beijing	Beijing
China	China-Japan Union Hospital of Jilin University	Changchun	Jilin
China	Hunan Provincial People'S Hospital	Changsha	Hunan
China	the Third Xiangya Hospital of Central South University	Changsha	Hunan
China	West China Hospital Sichuan University	Chengdu	Sichuan
China	the First Affiliated Hospital of Dalian Medical University	Dalian	Shandong
China	the Sixth Affiliated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong
China	the First Affiliated Hospital of Zhejiang University	Hangzhou	Zhejiang
China	First Affiliated Hospital of Jiamusi University	Jiamusi	Heilongjiang
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	Shandong General Hospital	Jinan Shi	Shandong
China	Shandong Provincial Qianfoshan Hospital	Jinan Shi	Shandong
China	Jinhua Hospital of Zhejiang University	Jinhua	Zhejiang
China	the 150th Central Hospital of Chinese PLA	Luoyang	Henan
China	the First Affiliated Hospital of Guangxi Medical University	Nanjing	Guangxi
China	the Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	Changhai Hospital	Shanghai	Shanghai
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning
China	Fourth Hospital of Hebei Medicial University	Shijiazhuang	Hebei
China	Shanxi Tumor Hospital	Taiyuan	Shanxi
China	the Second Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Hubei General Hospital	Wuhan	Hubei
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei
China	the First Affiliated Hospital of Xi'An Jiaotong University	Xi'an	Shanxi
China	the First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	the Second Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Chao Yang Hospital

Country where clinical trial is conducted

China, 

References & Publications (6)

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. — View 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. — View Citation

Ohman U. Prognosis in patients with obstructing colorectal carcinoma. Am J Surg. 1982 Jun;143(6):742-7. Review. — View 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. — View 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. Erratum in: Lancet Oncol. 2011 May;12(5):418. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease free survival		From date of randomization until the date of tumor recurrence or death from any cause, assessed up to 5 years
Primary	Overall survival		From date of randomization until the date of death from any cause, assessed up to 5 years
Primary	Rate of stoma formation		From date of randomization until the follow-up ended, assessed up to 5 years
Secondary	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
Secondary	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
Secondary	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
Secondary	Re-operation rate		From date of randomization until the follow-up ended, assessed up to 5 years
Secondary	Chemotherapy complete rate		From date of randomization until the chemotherapy ended, assessed up to 1 years
Secondary	Chemotherapy related complication		From date of randomization until the chemotherapy ended, assessed up to 1 years