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

Sponsor

Beijing Chao Yang Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT02972541

Collaborator

(none)

248

Enrollment

Locations

Arms

Duration (Months)

7.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Neoadjuvant Chemotherapy Stent Obstruction	Device: Stenting with neoadjuvant chemotherapy Device: Stenting with immediate Surgery	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

248 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Sep 30, 2016

Anticipated Primary Completion Date :

Dec 30, 2023

Anticipated Study Completion Date :

Dec 30, 2023

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

Surgical complication [From date of randomization until the first follow-up ended, assessed up to 30 days]
Including but not limited to: anastomotic leakage, wound infection, intra-abdominal sepsis,perioperative mortality, etc.
Rates of primary colorectal anastomosis [From date of randomization until the first follow-up ended, assessed up to 30 days]
The primary colorectal anastomosis was defined as: the patients received one-stage surgery and colorectal anastomosis.
R0 resection rate [From date of randomization until the first follow-up ended, assessed up to 30 days]
R0 resection is defined as negative resection margins and no residual tumor.
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Chaoyang Hospital, Capital Medical University	Beijing	Beijing	China	100020
2	Beijing Friendship Hospital	Beijing	Beijing	China	100020
3	Beijing Hospital	Beijing	Beijing	China	100020
4	Chinese People's Liberation Army General Hospital	Beijing	Beijing	China	100020
5	Xuanwu Hospital Capital Medical University	Beijing	Beijing	China	100020
6	Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing	China	100021
7	the Sixth Affiliated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong	China	510655
8	the First Affiliated Hospital of Guangxi Medical University	Nanjing	Guangxi	China	530021
9	Fourth Hospital of Hebei Medicial University	Shijiazhuang	Hebei	China	050011
10	First Affiliated Hospital of Jiamusi University	Jiamusi	Heilongjiang	China	154003
11	the 150th Central Hospital of Chinese PLA	Luoyang	Henan	China	471031
12	the First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan	China	450000
13	the Second Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan	China	450014
14	Hubei Cancer Hospital	Wuhan	Hubei	China	430000
15	Hubei General Hospital	Wuhan	Hubei	China	430060
16	Zhongnan Hospital of Wuhan University	Wuhan	Hubei	China	430071
17	the Third Xiangya Hospital of Central South University	Changsha	Hunan	China	410000
18	Hunan Provincial People'S Hospital	Changsha	Hunan	China	410005
19	China-Japan Union Hospital of Jilin University	Changchun	Jilin	China	130033
20	Shengjing Hospital of China Medical University	Shenyang	Liaoning	China	110004
21	the First Affiliated Hospital of Dalian Medical University	Dalian	Shandong	China	116011
22	Shandong Provincial Qianfoshan Hospital	Jinan Shi	Shandong	China	250014
23	Shandong General Hospital	Jinan Shi	Shandong	China	250021
24	Qilu Hospital of Shandong University	Jinan	Shandong	China	250022
25	the Affiliated Hospital of Qingdao University	Qingdao	Shandong	China	266000
26	Changhai Hospital	Shanghai	Shanghai	China	200000
27	Shanxi Tumor Hospital	Taiyuan	Shanxi	China	030013
28	the First Affiliated Hospital of Xi'An Jiaotong University	Xi'an	Shanxi	China	710061
29	West China Hospital Sichuan University	Chengdu	Sichuan	China	610041
30	the First Affiliated Hospital of Zhejiang University	Hangzhou	Zhejiang	China	310003
31	Jinhua Hospital of Zhejiang University	Jinhua	Zhejiang	China	321000
32	the Second Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang	China	325027

Sponsors and Collaborators

Beijing Chao Yang Hospital

Investigators

Principal Investigator: zhenjun wang, MD, Beijing Chao Yang Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Zhen Jun Wang, professor, Beijing Chao Yang Hospital

ClinicalTrials.gov Identifier:

NCT02972541

Other Study ID Numbers:

2016-161-1

First Posted:

Nov 23, 2016

Last Update Posted:

Feb 8, 2021

Last Verified:

Feb 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Additional relevant MeSH terms:

Colonic Neoplasms

Study Results

No Results Posted as of Feb 8, 2021