Cetuximab with anti-PD-1 and chemotherapy for right-sided colon cancer

A Multiple-Center,Single-arm Clinical Study of Cetuximab in Combination With Anti-PD-1 and mFOLFOX Treat For RAS/BRAF wt Locally Advanced or Metastatic Right-Sided Colon Cancer

This study is testing if a new combination of cetuximab, anti-PD-1, and chemotherapy can help people with advanced right-sided colon cancer do better than with standard treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 66 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Tongji Hospital (Academic / other)
• Drugs / interventions: chemotherapy, radiation, cetuximab
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT05468177 on ClinicalTrials.gov

What this trial studies

This study evaluates the efficacy and safety of cetuximab combined with anti-PD-1 and mFOLFOX6 in treating RAS/BRAF wild-type locally advanced or metastatic right colon cancer. It aims to determine if this combination can improve outcomes compared to standard treatments. The trial consists of two phases, with phase I assessing initial responses in 25 patients before proceeding to phase II, which will enroll a total of 66 patients if sufficient responses are observed. The approach leverages the potential sensitivity of right colon cancer to immune checkpoint inhibitors due to its unique microenvironment.

Who should consider this trial

Good fit: Ideal candidates include individuals with RAS and BRAF wild-type right colon adenocarcinoma who have locally advanced or oligometastatic disease.

Not a fit: Patients with non-RAS/BRAF wild-type colon cancer or those with severe comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective option for patients with advanced right-sided colon cancer.

How similar studies have performed: While there have been studies on cetuximab and immunotherapy in colorectal cancer, this specific combination approach is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. RAS and BARF wild-type right colon adenocarcinoma (cecum, ascending colon, transverse colon excluding splenic flexure) confirmed by histopathology;
2. Locally advanced right colon cancer should be assessed as T3 (invading muscularis propria ≥5mm) or T4 according to abdominal CT;
3. Metastatic right colon cancer should conforms to the definition of oligometastasis of colorectal cancer in ESMO guidelines: the number of organs involved is ≤2 (occasionally 3), and the number of metastases is usually ≤5 or occasionally more.
4. At least one measurable lesion according to RECIST1.1;
5. ECOG score 0-1;
6. The expected survival time is more than 3 months;
7. Adequate organ function: total bilirubin ≤1.5 x upper limit of normal (ULN) , aspartate aminotransferase and alanine aminotransferase ≤2.5 x ULN (if patient with liver metastasis, total bilirubin ≤3 x ULN, aminotransferase and alanine aminotransferase ≤5x ULN) ,alkaline phosphatase ≤2.5 x ULN (if liver metastases≤5x ULN, if bone metastases ≤10 x ULN);LDH \< 1500 U/L;Serum creatinine≤1.5 x ULN l or creatinine clearance rate ≤ 60 mL /min;ANC≥1.5×109 /L, platelet count ≥75×109 /L, Hb ≥90 g/L, WBC ≥3.0×109 /L;
8. Capable of providing informed consent, or if not capable, a legally authorized representative is capable of providing informed consent.

Exclusion Criteria:

* 1.Early stage right colon cancer. 2. Received chemotherapy or biotherapy in the past . 3. uncontrollable infection, or received antibiotic treatment within 72 hours prior to receive chemotherapy; 4. Myelodysplastic syndrome or other hematopoietic abnormalities; 5. Other malignant tumors (except carcinoma in situ and basal cell carcinoma) during this year; 6. Patients with central nervous system metastasis; 7.≥ CTCAE Grade 2 unrecovered AEs due to prior treatment (excluding anemia, hair loss, skin pigmentation).Patients with unrecovered neurotoxicity ≥ CTCAE grade 3 due to platinum-based drugs.

  8. Other diseases, such as active tuberculosis, infect HIV, AIDS, hepatitis B (patient withHBV-DNA \<500IU/ml,and normal liver function can be included), positive test for hepatitis C virus, uncorrectable electrolyte disorder;ascites, pleural effusion or hydropericardium that required drainage in the past 4 weeks.With intestinal obstruction, gastrointestinal bleeding, pulmonary fibrosis or interstitial pneumonia, renal failure, hepatic failure , or cerebrovascular disease.

  9. Uncontrolled diabetes was defined as HbA1c \>7.5% after the use of antidiabetic drugs, or uncontrolled hypertension was defined as systolic/diastolic blood pressure \>140/90 mmHg after the use of antihypertensive drugs.

  10. Myocardial infarction,severe/unstable angina, NYHA III or IV congestive heart failure within the past 12 months.

  11. Patients who are allergic to the therapeutic drugs in this study; 12. With mental or nervous system diseases who are unable to cooperate; 13. Pregnant or lactating women;Childbearing age women refuse to accept contraceptive measures; 14.Active autoimmune disease, a history of autoimmune disease, accepting corticosteroid or immunosuppressants, or accepting hormone replacement therapy (such as thyroxine, insulin, etc).

  15. Received live vaccine within 30 days (seasonal influenza vaccine is allowed because it is inactivated) 16.Treated with any other investigational drug or participated in another interventional clinical trial within 30 days of the screening period; undergo surgery within 30 days (except for diagnostic biopsy, surgical incision should be completely healed prior to administration of the study drug).Received radiation therapy within 30 days.

  17. Other serious medical conditions made the investigator consider the patients ineligible for inclusion.

Where this trial is running

Wuhan, Hubei

• Tongji Hospital, Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)

Study contacts

• Study coordinator: Guihua Wang

Conditions Colonic Neoplasms; neoadjuvant chemotherapy; cetuximab; right colon cancer; immunotherapy