Serplulimab Combined with CAPEOX + Celecoxib As Neoadjuvant Treatment for Locally Advanced Rectal Cancer

Phase 2

Recruiting

• Conditions: PMMR; MSS; MSI-L; Locally Advanced Rectal Carcinoma
• Interventions: Drug: Serplilumab; Drug: Capecitabine; Drug: Oxaliplatin; Drug: Celecoxib

• Registration Number: NCT05731726
• Lead Sponsor: Zhejiang University

Brief Summary

Colorectal cancer of Mismatch Repair-proficient (pMMR)/ Microsatellite Stability (MSS) accounts for approximately 85% of all colorectal cancer patients, which might be insensitive to immunotherapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy, such as CAPEOX regimen, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Celecoxib, a COX-2 inhibitor, can improve the immune microenvironment and have a potential to synergy with immunotherapy. Chemotherapy can improve the immunogenicity of cancer cells that might enhance the efficacy of immunotherapy. The aim of this study is to explore whether chemotherapy and cyclooxygenase (COX) inhibitors combined with anti-PD-1 monoclonal antibody (mAb) could improve efficacy for resectable colorectal cancer patient with the pMMR/MSS phenotype.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-02-07
• Study First Submitted QC: 2023-02-07
• Study First Posted: 2023-02-16
• Study Start: 2023-02-22
• Status Verified: 2024-11
• Last Update Submitted: 2024-12-04
• Last Update Posted: 2024-12-09
• Primary Completion: 2025-12-20
• Study Completion: 2025-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Willing and able to provide written informed consent.
2. Male or female subjects ≧ 18 years ≦ 75 of age.
3. Histological or cytological documentation of adenocarcinoma of the rectum.
4. No previous any systemic anticancer therapy for rectal cancer disease.
5. The lower margin of the tumor is less than 10cm from the anus verge.
6. cT2N1-2M0, cT3N0-2M0, cT4N0-2M0 MSS with MRF(-) assessed by MRI.
7. Primary tumor can be detected by CT or MRI.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
9. Eligible tumor tissues were identified for MSI/MMR assays.
10. Hepatitis B Surface Antigen (HBsAg) (-).
11. If HBsAg (+) , HBV-DNA must be less than 2500 copies/mL or 500 IU/mL to be enrolled.
12. Patients with HCV antibody (-) or HCV-RNA negative can be enrolled. Aspartate aminotransferase (AST) must be ≤ 3 x ULN for the lab. If HCV-RNA is positive, patients with both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) performed ≤3×ULN could be enrolled. Patients infected with both hepatitis B virus and hepatitis C virus should be excluded (positive for HBsAg or HBcAb and positive for HCV antibodies).

Exclusion Criteria

1. Patients with recurrent rectal cancer or a history of pelvic radiotherapy.
2. Patients with a history of inflammatory bowel disease.
3. Patients with acquired immunodeficiency syndrome (AIDS-related illnesses) or known human immunodeficiency virus (HIV) disease (HIV1 antibody, HIV2 antibody, HTLV1 antibody positive) should be excluded.
4. Patients who are preparing for or have previously received an organ or bone marrow transplant.
5. History of myocardial infarction, poorly controlled arrhythmias (including QTc interval ≥470 ms in women) in the 6 months prior to enrollment (QTc interval calculated by Fridericia formula).
6. According to New York College of Cardiology (NYHA) standards for Grade III-IV cardiac insufficiency or cardiac color ultrasound: left ventricular ejection fraction (LVEF) <50%.Poor hypertension control (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg), a past hypertensive crisis or hypertensive encephalopathy.
7. Poor hypertension control (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg), a past hypertensive crisis or hypertensive encephalopathy.
8. Patients had undergone major surgery within 28 days prior to enrollment. Patients with tumor biopsy or lymph node dissection biopsy were admitted. Patients undergoing enterostomy due to intestinal obstruction were admitted.
9. The patients had previously been treated with other antibodies/drugs that target immune checkpoints, such as PD-1, PD-L1, and cytotoxic T lymphocyte-associated Antigen 4 (CTLA-4).
10. Patients are participating in other clinical studies, or plan to start this study treatment less than 14 days from the end of the previous clinical study.
11. Uncontrolled tumor-related pain.
12. A known history of severe allergy to any monoclonal antibody.
13. Known to be allergic to any oxaliplatin and capecitabine ingredients.
14. Pregnant or lactating women.
15. The investigators determined that the patient had other factors that might have led to the early termination of the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Serplulimab+CAPEOX+celecoxib	Serplilumab	articipants will receive serplulimab 300 mg every 3 weeks (Q3W) concurrently with CAPEOX regimen: Oxaliplatin(130mg/m2) on day 1 of each cycle and Capecitabine, 1000mg/m2, PO, BID, day1-14, q3w and celecoxib, 200mg, PO, BID, day1-21, q3w. Treatment repeats every 3 weeks for 6-8 cycles followed by surgery (total mesorectal excision, TME).
Serplulimab+CAPEOX+celecoxib	Capecitabine	articipants will receive serplulimab 300 mg every 3 weeks (Q3W) concurrently with CAPEOX regimen: Oxaliplatin(130mg/m2) on day 1 of each cycle and Capecitabine, 1000mg/m2, PO, BID, day1-14, q3w and celecoxib, 200mg, PO, BID, day1-21, q3w. Treatment repeats every 3 weeks for 6-8 cycles followed by surgery (total mesorectal excision, TME).
Serplulimab+CAPEOX+celecoxib	Oxaliplatin	articipants will receive serplulimab 300 mg every 3 weeks (Q3W) concurrently with CAPEOX regimen: Oxaliplatin(130mg/m2) on day 1 of each cycle and Capecitabine, 1000mg/m2, PO, BID, day1-14, q3w and celecoxib, 200mg, PO, BID, day1-21, q3w. Treatment repeats every 3 weeks for 6-8 cycles followed by surgery (total mesorectal excision, TME).
Serplulimab+CAPEOX+celecoxib	Celecoxib	articipants will receive serplulimab 300 mg every 3 weeks (Q3W) concurrently with CAPEOX regimen: Oxaliplatin(130mg/m2) on day 1 of each cycle and Capecitabine, 1000mg/m2, PO, BID, day1-14, q3w and celecoxib, 200mg, PO, BID, day1-21, q3w. Treatment repeats every 3 weeks for 6-8 cycles followed by surgery (total mesorectal excision, TME).

Primary Outcome Measures

Name	Time	Method
Pathological complete response rates	1 year	Proportion of patients experiencing a pCR to perioperative PD-1 antibody

Secondary Outcome Measures

Name	Time	Method
Major pathological response rates	1 year	The proportion of patients experiencing a major pathological response to perioperative PD-1 antibody
Rate of clinical complete response rate (cCR)	1 year	Proportion of patients experiencing a cCR to perioperative PD-1 antibody
R0 resection rates	1 year	The proportion of patients achieved a complete resection with negative margin
Treatment-related adverse events.	1 year	Assessed by evaluation of treatment-related adverse events.
Detection of MRD	1year	To detect ctDNA in peripheral blood before and after treatment
single cell sequence	1year	Use single cell sequence to describe changes in the microenvironment of rectal cancer before and after treatment
Disease Free Survival	3years	Defined as the interval from enrollment to locoregional or metastatic recurrence or the appearance or a secondary colorectal cancer or death, whichever occurs first

Trial Locations

Locations (1)

Second Affiliated Hospital School of Medicine Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China