Neoadjuvant treatment for locally advanced rectal cancer using Serplulimab, CAPEOX, and Celecoxib

A Phase II Study to Explore the Neoadjuvant Treatment of Serplulimab Combined With CAPEOX + Celecoxib in the Treatment of Locally Advanced Rectal Cancer

This study is testing a new treatment combining an immune therapy and chemotherapy to see if it can help people with locally advanced rectal cancer before surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Zhejiang University (Academic / other)
• Drugs / interventions: pembrolizumab, Chemotherapy, immunotherapy
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT05731726 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the combination of Serplulimab, a monoclonal antibody, with the chemotherapy regimen CAPEOX (Capecitabine and Oxaliplatin) and the COX-2 inhibitor Celecoxib as a neoadjuvant treatment for patients with locally advanced rectal cancer. The study aims to enhance the immune response against cancer cells and improve treatment efficacy by utilizing both immunotherapy and chemotherapy. Eligible participants will be those with specific tumor characteristics and no prior systemic anticancer therapy for rectal cancer. The trial will assess the safety and effectiveness of this combined approach in improving patient outcomes.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 to 75 with histologically confirmed adenocarcinoma of the rectum who have not received prior systemic anticancer therapy.

Not a fit: Patients with rectal cancer who have previously undergone systemic anticancer therapy or have tumors that do not meet the specified criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective neoadjuvant option for patients with locally advanced rectal cancer, potentially leading to better surgical outcomes and survival rates.

How similar studies have performed: While the combination of immunotherapy and chemotherapy is being explored in various contexts, this specific approach is novel and has not been extensively tested in this patient population.

Eligibility criteria

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 or intolerance 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.

Where this trial is running

Hangzhou, Zhejiang

• Second Affiliated Hospital School of Medicine Zhejiang University — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Kefeng Ding, doctor

Conditions pMMR; MSS; MSI-L; Locally Advanced Rectal Carcinoma; Rectal cancer; Serplulimab; Celecoxib; CAPEOX