Bevacizumab, sintilimab, cetuximab and irinotecan in refractory RAS wild-type metastatic colorectal cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a randomized, multicenter, open-label phase II study in patients with RAS wild-type, MSS metastatic colorectal cancer who progressed after at least two prior therapies. Participants are assigned to cetuximab plus irinotecan with or without bevacizumab, with the addition of sintilimab in the experimental arm. The primary endpoint is objective response rate, with secondary endpoints including progression-free survival, overall survival, and safety. The study explores whether combining anti-VEGF therapy and PD-1 blockade can enhance response compared with cetuximab and irinotecan alone. The target sample size is about 160 participants, analyzed by intention-to-treat. Eligible patients are adults with unresectable disease, adequate organ function, and prior exposure to standard therapies including fluoropyrimidine, irinotecan, and bevacizumab.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Metastatic and unresectable colorectal adenocarcinom;
* RAS wild-type and MSS tumor;
* Measurable lesions;
* Failed to at least two lines of standard treatment containing fluoropyrimidine, irinotecan and bevacizumab;
* Eastern Cooperative Oncology Group performance status 2 or less;
* White blood cell≥ 3\*10\^9/L, neutrophil≥ 1.5\*10\^9/Lplatelet count≥75\*10\^9/L, hemoglobin≥60g/L;
* Total serum bilirubin≤upper limit of normal (ULN), alanine aminotransferase and aspartate aminotransferase ≤ 2.5\*ULN or ≤5\*ULN for subjects with liver metastasis;
* Creatinine ≤ ULN or creatinine clearance ≥ 80 mL/min;
* Urinary protein negative or 24-hour urinary protein ≤ 2g;
* Activated partial thromboplastin time≤ULN and international normalized ratio≤1.5;
* Any major surgery ≥ 4 weeks and any minor surgery ≥ 1 week and fully recovered from the procedure;
* Life expectancy \> 3 months;
* Provide fully informed written consent;

Exclusion Criteria:

* Other aggressive malignancies within 3 years (Exceptions: non-melanoma skin cancer or carcinoma-in-situ of the cervix that has been treated);
* Allergy or intolerance to any of the study drugs;
* Human immunodeficiency virus positive;
* Concurrent anti-cancer therapy including radiation therapy, chemotherapy, targeted agents or biological agents not otherwise specified within two weeks;
* Malignant bowel obstruction;
* Prior treatment with PD-1 antibody;
* Autoimmune diseases;
* Significant bleeding events or pre-existing bleeding diathesis within 6 months (unless the source of bleeding has been resected);
* Gastrointestinal perforation within 12 months;
* Serious or non-healing wound, ulcer, or bone fracture;
* Blood pressure \>= 160/90 mmHg after active anti-hypertensive therapy;
* Arterial or venous thrombotic or embolic events within 6 months (including but not limited to transient ischemic attack, cerebrovascular accident, unstable angina or myocardial infarction);
* Uncontrolled illness including active infection, symptomatic congestive heart failure, cardiac arrhythmia, respiratory failure, symptomatic pulmonary fibrosis, interstitial pneumonitis or psychiatric illness that may interfere with the conduct of the study;
* Known or suspected brain or central nervous system (CNS) metastases, or carcinomatous meningitis;
* Any of the following: pregnant, nursing, childbearing potential but unwilling to employ contraception.

Where it's running

• Guangdong Provincial People's Hospital
  Guangzhou, Guangdong, China Recruiting

Study contacts

• Principal investigator: Jian Xiao, MD — Guangdong Provincial People's Hospital
• Study coordinator: Jian Xiao, MD
• Email: xiaojian@gdph.org.cn
• Phone: 86-20-83525975

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.