Camrelizumab Combined With Neoadjuvant Chemotherapy After Stent Placement for Left-Sided Obstructive Colonic Cancer (NACSOC-02)

Camrelizumab Combined With Neoadjuvant Chemotherapy After Stent Placement Versus Surgery Alone for Left-Sided Obstructive Colonic Cancer

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. Immunotherapy has proven to be highly effective as first-line treatment of metastatic colorectal cancer (CRC). And immunotherapy also has emerged as a neoadjuvant approach, possibly changing treatment strategy for both primary resectable and metastatic CRC. We hypothesis that, regardless of the MSI state, immunotherapy (Camrelizumab, an anti-PD-1 antibody) combined with chemotherapy after stenting may improve overall survival by eradicating micrometastasis. Moreover, immunotherapy (Camrelizumab, an anti-PD-1 antibody) combined with 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, and furthermore, improve OS and PFS.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Obstruction; Immunotherapy; Neoadjuvant Chemotherapy; Stent
• Intervention / Treatment: Drug: Immunotherapy (Camrelizumab)

Detailed Description

We hypothesis that, regardless of the MSI state, immunotherapy combined with immediate chemotherapy after stenting may improve overall survival by eradicating micrometastasis. Moreover, immunotherapy (Camrelizumab, an anti-PD-1 antibody) combined with 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, and furthermore, improve OS and PFS.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jia Gang Han, MD; Phone Number: +861085231604; Email: hjg211@163.com
• Study Contact Backup: Name: Zhi Wei Zhai, MD; Phone Number: +861085231328; Email: zhaizhiwei@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100020
      • Recruiting
      • Beijing Chaoyang Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 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 3.0×10# /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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Immunotherapy group; After clinical success of colonic stenting, regardless of the MSI state all patients will receive Immunotherapy (Camrelizumab 200mg) for 2 cycles compined with neoadjuvant chemotherapy with mFOLFOX6 regimen for 3 cycles or CapeOx regimen for 2 cycles. Patients will undergo surgery 2-3 weeks after the last cycle of chemotherapy, type and extent of the surgery will be selected by the surgeon.

Drug: Immunotherapy (Camrelizumab); After clinical success of colonic stenting, regardless of the MSI state, patients will receive Immunotherapy (Camrelizumab 200mg) for 2 cycles compined with neoadjuvant chemotherapy with mFOLFOX6 regimen for 3 cycles or CapeOx regimen for 2 cycles. Patients will undergo surgery 2-3 weeks after the last cycle chemotherapy; Other Names: Chemotheray (CAPOX or mFOLFOX6)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete remission	No tumor cell found in surgical specimens	2 weeks after patients received radical operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival	No tumor regrowth or recurrence or metastasis found	3 years after operation
Overall Survival	Survive during following	3 years after operation

Collaborators and Investigators

• Sponsor: Beijing Chao Yang Hospital
• Investigators: Principal Investigator: Zhen Jun Wang, MD, Beijing Chao Yang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2021
• Primary Completion (Anticipated): December 30, 2023
• Study Completion (Anticipated): December 30, 2026

Study Registration Dates

• First Submitted: January 10, 2022
• First Submitted That Met QC Criteria: January 10, 2022
• First Posted (Actual): January 21, 2022

Study Record Updates

• Last Update Posted (Estimate): February 21, 2023
• Last Update Submitted That Met QC Criteria: February 19, 2023
• Last Verified: February 1, 2023

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: 2021-12-24

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No