XELOX +Bev +Tislelizumab for First-line Treatment of MSS/pMMR RAS-mutated mCRC

Launched by CANCER INSTITUTE AND HOSPITAL, CHINESE ACADEMY OF MEDICAL SCIENCES · Jul 21, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment combination for patients with a specific type of advanced colorectal cancer known as metastatic colorectal adenocarcinoma that has certain genetic mutations (RAS mutations). The researchers want to find out if the combination of three drugs—XELOX (which includes oxaliplatin and capecitabine), Bevacizumab (a drug that helps prevent the growth of blood vessels that feed tumors), and Tislelizumab (an immunotherapy drug)—is more effective and safe compared to standard chemotherapy. The goal is to improve the body’s immune response against the cancer by first making the tumor more recognizable to the immune system.

To participate in the trial, patients should be between 65 and 74 years old, have confirmed RAS-mutated metastatic colorectal cancer that cannot be surgically removed, and not have received any prior treatments for their cancer after it spread. Participants can expect to take the study medications and be monitored closely for any side effects or improvements in their condition. It’s important for potential participants to fully understand the trial and provide consent, as well as to use effective birth control if they are able to have children.

Gender

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Eligibility criteria

• Inclusion Criteria:
• • 1. Histologically confirmed initially unresectable MSS/pMMR-type RAS-mutant metastatic colorectal adenocarcinoma;
• • 2. ECOG score of 0 or 1;
• • 3. Ability to swallow oral medications;
• • 4. Have at least one measurable lesion (according to RECIST v1.1 standard);
• • 5. No anti-tumor treatment has been received after recurrence and metastasis;
• • 6. Neoadjuvant or adjuvant chemotherapy containing fluorouracil drugs is allowed before or after radical resection of colorectal cancer, but the treatment needs to be completed for ≥ 6 months; if oxaliplatin is used in neoadjuvant or adjuvant chemotherapy, it includes The oxaliplatin regimen needs to be completed for ≥12 months;
• • 7. Adequate organ function: On the premise of no component blood transfusion within 14 days: white blood cells ≥ 3.5\*10\^9/L and neutrophils ≥ 1.5\*10\^9/L, hemoglobin ≥ 90g/L, platelets ≥ 100\* 10\^9/L; serum bilirubin ≤ 1.5 times the normal value, alanine aminotransferase (ALT) ≤ 2.5 times the normal value, aspartate aminotransferase (AST) ≤ 2.5 times the normal value; Urinary protein \<2+. Or urine protein 2+ but 24-hour urine protein quantity ≤ 1 g; serum creatinine ≤ 1.5 times of normal value, creatinine clearance rate ≥ 60ml/min; Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥ lower limit of normal value (50%);
• • 8. Expected survival period ≥ 3 months;
• • 9. Patients fully understand this research, voluntarily participate in this clinical trial and sign an informed consent;
• • 10. Women with reproductive potential (\< 2 years after the last menstrual period) and men use effective contraceptive methods until half a year after the last treatment.
• Exclusion Criteria:
• • 1. Previously received bevacizumab or anti-CTLA4, anti-PD-1/PD-L1 therapeutic antibodies or pathway-targeted drugs;
• • 2. Received radiotherapy within 4 weeks before the evaluation;
• • 3. Symptomatic peripheral neuropathy \> grade 2 (CTCAE5.0 standard);
• • 4. Received live vaccine or systemic immune stimulant (including but not limited to interferon or interleukin 2) within 1 month;
• • 5. HIV-positive and other immunodeficiency diseases;
• • 6. Active hepatitis B or hepatitis C (except for those who have been infected or cured before, that is, HBsAg negative and hepatitis B core antigen anti-HBc antibody positive; except for hepatitis C patients whose HCV RNA is negative by PCR);
• • 7. Existing autoimmune diseases or other diseases that require immunosuppressant treatment, except for type 1 diabetes; except for hypothyroidism that only requires hormone replacement therapy; skin diseases that do not require systemic treatment (such as vitiligo, psoriasis, alopecia areata); inhaled or topical steroids or equivalent steroids in excess of 10 mg prednisone per day, except for inactive autoimmune disease on adrenal replacement therapy;
• • 8. Received systemic hormone therapy or treatment with a daily dose of more than 10 mg prednisone equivalent dose or other forms of immunosuppressive treatment within 7 days, but inhaled or topical steroids or daily application of more than 10 mg prednisone, etc. Except for inactive autoimmune diseases treated with adrenal replacement therapy with potent steroids;
• • 9. Have a history of organ transplantation;
• • 10. Uncontrolled central nervous system (CNC) metastasis (symptomatic or metastatic sites are midbrain, pons, medulla or spinal cord) or other central nervous system diseases;
• • 11. Those who have undergone major surgery, open biopsy or obvious traumatic trauma within 1 month, or who may need major surgery during the study period; those who have undergone open biopsy or obvious traumatic trauma, or may need major surgery during the study period;
• • 12. Combined with other malignant tumors other than intestinal cancer (except cured basal cell carcinoma or squamous cell carcinoma of the skin and carcinoma in situ of the cervix; the treatment of other malignant tumors has been completed for more than 1 year, and there is no clinical and imaging evidence of recurrence or progression except);
• • 13. Combined active and refractory infection;
• • 14. Cardiovascular diseases with clinical significance, such as cardiovascular accident (CVA) (≤ 6 months before treatment), myocardial infarction (≤ 6 months before treatment), unstable angina, chronic heart failure of NYHA ≥ 2 (CHF), uncontrolled arrhythmia; uncontrolled hypertension; thromboembolic or bleeding events within 6 months before treatment;
• • 15. Evidence of causing coagulation disease;
• • 16. With dysphagia, active peptic ulcer, complete or incomplete intestinal obstruction, active gastrointestinal bleeding, perforation, malabsorption syndrome or uncontrollable gastrointestinal inflammatory disease (such as Crohn's disease or ulcerative colon inflammation);
• • 17. Severe unhealed wounds/ulcers or severe fractures;
• • 18. Any serious acute or chronic medical condition that may affect the patient's participation in the study or interfere with the interpretation of the study results;
• • 19. There are mental illnesses, serious social and psychological illnesses, or researchers believe that there are factors that may affect research compliance;
• • 20. Pregnant or lactating women;
• • 21. No therapeutic anticoagulant or antiplatelet drugs or NSAIDs (aspirin ≤ 325 mg/day allowed);
• • 22. Severe allergic reaction to the test drug;
• • 23. Reluctance to use alternative therapies such as (but not limited to) bisphosphonates if receiving RANKL inhibitors (eg, denosumab).