Cetuximab Plus Capecitabine as Maintenance Treatment in RAS and BRAF wt Metastatic Colorectal Cancer

Inclusion Criteria:

1. Written informed consent prior to performance of any study procedure.
2. Patient must be ≥18 years of age, at the time of signing the informed consent.
3. Patients who have histologically or cytologically confirmed adenocarcinoma of thecolon or rectum, excluding appendix carcinoma or anal canal carcinoma, with RAS andBRAF wild-type mutation status.
4. Patients who received only FOLFOX plus cetuximab as first-line induction treatmentafter diagnosis of mCRC.
5. Having completed FOLFOX plus cetuximab for 9 cycles as induction treatment (in thefirst cycle, they could be treated with FOLFOX alone for waiting the results ofgenetic test) without discontinuation for toxicity, of cetuximab or fluorouracil oroxaliplatin and achieved disease control (including CR/PR and SD) and are progressionfree at the start of maintenance therapy.
6. At least one lesion(s), which is considered as unresectable at start of maintenancetherapy (mCRC patients with resectable lesion(s) after induction treatment can beenrolled if they are willing to choose maintenance therapy). Patients who achieved CRand had no measurable lesion after induction treatment can be enrolled in this study.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
8. Life expectancy of at least 12 weeks in the opinion of the investigator.
9. Laboratory requirements

• Neutrophils ≥1.5×109/L, platelets ≥75×109/L, and hemoglobin ≥9 g/dL;
• Total bilirubin ≤1.5×upper limit of normal (ULN); aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and/or alanineaminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT)
• 2.5×ULN (≤5×ULN in case of liver metastases); alkaline phosphatase
• 2.5×ULN (≤5×ULN in case of liver metastases, ≤10×ULN in case of bonemetastases); lactate dehydrogenase (LDH) <1500 U/L;
• Creatinine clearance (calculated according to Cockcroft and Gault) >60 mL/min orserum creatinine ≤1.5×ULN.

Exclusion Criteria:

1. Having received chemotherapy for mCRC other than induction therapy with FOLFOX pluscetuximab, except for adjuvant therapy that has ended >9 months (oxaliplatin- basedchemotherapy) or >6 months (oxaliplatin-free chemotherapy), prior to the start of theinduction treatment.
2. Other concurrently active malignancies, excluding malignancies that are disease freefor more than 5 years or carcinoma-in-situ deemed cured by adequate treatment.Patients who are definitely detected as dMMR/MSI-H at the start of induction therapy.
3. Known brain metastasis or leptomeningeal metastasis. Patients with neurologicalsymptoms should undergo brain computed tomography (CT)/ magnetic resonance imaging (MRI) to exclude metastases.
4. Unresolved toxicity greater than or equal to Common Terminology Criteria for AdverseEvents (CTCAE) Grade 2 attributed to any prior therapies (excluding anemia, alopecia,skin pigmentation). Patients with platinum induced neurotoxicity greater than or equalto CTCAE Grade 3 should be excluded.
5. Ascites, pleural effusion or pericardial fluid requiring drainage in last 4 weeks.
6. Intestinal obstruction, major gastrointestinal hemorrhage or other diseases notsuitable for maintenance treatment in this study as assessed by the investigatorwithin 2 weeks prior to enrollment.
7. Diabetes and hypertension as assessed by the investigator as not eligible for thesubsequent maintenance treatment in this study.
8. Myocardial infarction within the last 12 months, severe/unstable angina, symptoms ofclass III or IV congestive heart failure per New York Heart Association (NYHA)classification.
9. Previous hypersensitivity to any of the study drugs (cetuximab or capecitabine).
10. Deficiency in dihydropyrimidine dehydrogenase (DPD) as manifested by known medicalhistory of fluorouracil adverse reactions.
11. Known infection with human immunodeficiency virus (HIV), acquired immunodeficiencysyndrome (AIDS)-related illness, or active hepatitis B (positive HBsAg and HBV-DNA ≥ 2000 IU/mL or 104 copies/mL) or hepatitis C. Patients with previously confirmedCOVID-19 infection, including severe, mild, asymptomatic, and recovered patients.
12. Patients with active autoimmune disorders requiring treatment or history of organtransplantation requiring immunosuppressive therapy.
13. Psychiatric disease that may increase the risk associated with study participation orstudy drug administration or may interfere with the interpretation of study results.
14. Treatment with any of the following within the specified time frame prior to studydrug administration

• Major surgery within 4 weeks (excluding diagnostic biopsy, the surgical incisionshould be fully healed prior to study drug administration);
• Radiotherapy within 4 weeks;
• Anti-cancer therapy other than protocol-specified induction therapy orparticipation in other clinical studies within 4 weeks.
• Anti-tumor traditional Chinese medicine within 2 weeks (such as Cantharidin,Cinobufacini).

15. Pregnant (as determined by serum human chorionic gonadotropin [hCG] test) or lactatingfemale, or female planning to become pregnant during treatment and for 2 months afterthe end of treatment with cetuximab and 6 months after the end of capecitabine. Womanof childbearing potential (WOCBP) with either positive or no pregnancy test atbaseline. WOCBP or sexually active men not willing to use contraception during studyand for at least 3 months after completion of cetuximab and 6 months after completionof capecitabine. Postmenopausal women must have been amenorrheic for at least 12months to be considered of non-childbearing potential.
16. Presence of other serious disease or social circumstances that precludes patientenrollment in the opinion of the investigator.