Combining Sintilimab with XELOX and Bevacizumab for Advanced Colorectal Cancer

A Randomized, Open, Multicenter Phase III Clinical Trial of Combination of Sintilimab Injection (IBI308) and XELOX+Bevacizumab Compared With XELOX+Bevacizumab as 1st Line Therapy of RAS-Mutant Metastatic Colorectal Cancer

This study is testing a new combination of treatments for patients with advanced colorectal cancer to see if it can help them better fight the disease.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 436 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (Academic / other)
• Drugs / interventions: chemotherapy, radiation, Sintilimab, bevacizumab
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT05171660 on ClinicalTrials.gov

What this trial studies

This phase III clinical trial investigates the effectiveness of sintilimab, a PD-1 inhibitor, combined with XELOX chemotherapy and bevacizumab as a first-line treatment for patients with RAS-mutant metastatic colorectal cancer. The study aims to enhance anti-tumor immunity through this combination therapy in patients who have not previously received treatment. Participants will receive a regimen every three weeks to evaluate the treatment's efficacy and safety.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with confirmed metastatic colorectal adenocarcinoma and RAS mutations.

Not a fit: Patients with colorectal cancer that is resectable or those without RAS mutations may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for patients with RAS-mutant metastatic colorectal cancer.

How similar studies have performed: Other studies have shown promising results with similar combinations of PD-1 inhibitors and chemotherapy in treating advanced cancers.

Eligibility criteria

Inclusion Criteria:

1. Male or female, age ≥ 18 years old, ≤ 75 years old
2. Metastatic colorectal adenocarcinoma confirmed by histology, metastases cannot be removed
3. RAS mutation
4. ECOG 0 to 1
5. Life expectancy is at least 12 weeks
6. Hematological examination absolute neutrophil count (ANC)\>1.5×109/L, hemoglobin\>8g/dL and platelet\>100×109/L (according to the normal value of clinical trial center)
7. Prothrombin time (PT) \< 1.5 times the upper limit of normal value and normal thromboplastin time (APTT) \< 1.5 times the upper limit of normal value
8. Laboratory examination, serum creatinine is less than or equal to 1.5 times the upper limit of the normal reference range (if serum creatinine is elevated, 24 hours of urine must be collected, except for 24 hours creatinine clearance \> 50ml/min)
9. When there is no liver metastasis, ALT or AST is less than or equal to 2.5 times the upper limit of the normal value reference range, serum total bilirubin is less than or equal to 1.5 times the upper limit of the normal value reference range; for patients with liver metastasis, ALT or AST is less than or equal to 5 times the upper limit of the normal value reference range, serum total bilirubin is less than or equal to 3 times the upper limit of the normal value reference range
10. Women of childbearing age must be willing to use adequate contraception during study drug treatment
11. Informed consent has been signed
12. According to the definition of RECIST 1.1, the investigator determined that the patient had a measurable disease. Tumor lesions located in previous radiotherapy areas are considered measurable if they demonstrate progression.

Exclusion Criteria:

1. Active autoimmune disease requiring systemic treatment occurred in the previous 2 years.
2. Diagnosed as immunodeficiency or experimental treatment is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose. After consultation with the sponsor, the use of a physiological dose of corticosteroids may be approved.
3. Adverse events caused by anti-tumor monoclonal antibodies (mAbs) within 4 weeks prior to study day 1 or drugs received 4 weeks prior to the study have not recovered.
4. Adverse events caused by chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1, or previously received drugs, have not recovered (ie, ≤1 or reached baseline levels).

   Other malignancies that are progressing or require active treatment are known. Except for basal cell carcinoma, cutaneous squamous cell carcinoma, or cervical carcinoma in situ that have undergone radical treatment.
5. Active central nervous system (CNS) metastasis and/or cancerous meningitis are known to exist.
6. There are active infections that require systemic treatment.
7. It is possible to confuse the test results, the medical history or disease evidence, the treatment or laboratory value abnormalities that hinder the subject's full participation in the study, or the investigator believes that participating in the study is not in the best interests of the subject.
8. There are known mental or substance abuse disorders that may have an impact on compliance with test requirements.
9. Female subjects who are pregnant or lactating, or who are expected to be pregnant during the planned trial period (from 120 days after screening visits to 120 days after the last dose of study treatment, or 180 days after the last dose of study treatment), or Male subjects whose spouse is pregnant.
10. A history of infection with human immunodeficiency virus (HIV) (HIV 1/2 antibody) is known.
11. Active hepatitis B or C.
12. Live vaccines were vaccinated within 30 days of the start date of the study treatment plan.
13. RAS wild type

Where this trial is running

Hangzhou, Zhejiang

• Xuefeng Fang — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Ying Yuan — 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China
• Study coordinator: Xuefeng Fang

Conditions Colorectal Cancer Stage IV; Colorectal Cancer Stage IV,; RAS gene mutation; Microsatellite stable