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

Study Overview
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Brief Summary
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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.

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

Conditions
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Colorectal Cancer, Neoadjuvant Chemotherapy, Stent, Obstruction

Intervention / Treatment
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* Device: Stenting with neoadjuvant chemotherapy
* Device: Stenting with immediate Surgery


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stenting with neoadjuvant chemotherapy<br>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<br>* 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.<br>|
| Active Comparator: Stenting with Immediate Surgery<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |