Safety and Efficacy of Pembrolizumab in Combination with Bevacizumab + CapeOX in the Neoadjuvant Treatment of RAS-mutated, BRAF Wild-type, Microsatellite-stabilized, Locally Advanced Colorectal Cancer

Launched by YANGJIANJUN · Aug 10, 2024

Keywords

ClinConnect Summary

This clinical trial is looking at a new treatment approach for patients with locally advanced colorectal cancer that has specific genetic characteristics (RAS mutations and BRAF wild-type). The study will test a combination of three medications: pembrolizumab, bevacizumab, and CapeOX (which includes oxaliplatin and capecitabine). The main goal is to see how effective this treatment is in shrinking the cancer before surgery, as measured by a complete absence of cancer cells in tissue samples.

To participate in the trial, patients need to be at least 18 years old and have been diagnosed with the specified type of colorectal cancer. They must not have received any prior cancer treatment and should have certain health parameters within normal limits. If you join this study, you can expect to receive the combination therapy for 2 to 4 cycles, followed by surgery. Throughout the trial, doctors will closely monitor your health and any side effects from the treatment. It's important to note that this study has received ethical approval, and all participants will need to provide informed consent before starting.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Age: ≥18 years;
• • Confirmed RAS mutation and BRAF wild-type in LACRC by pathological histology or genetic sequencing.;
• • ECOG Performance Status (PS) score of 0 or 1;
• • Previously untreated;
• • Microsatellite-stable status;
• • Hematological parameters within normal limits: White blood cell count ≥4×10\^9/L; Absolute neutrophil count ≥1.5×10\^9/L; Platelets ≥100×10\^9/L. Hemoglobin ≥90g/L;
• • Normal renal function: Serum creatinine ≤1.5× upper limit of normal (ULN) or creatinine clearance (CrCl) \>60 mL/min (calculated using Cockcroft-Gault formula): Female CrCl = (140 - age) × weight (kg) × 0.85 / (72 × Scr mg/dl)；Male CrCl = (140 - age) × weight (kg) × 1.00 / (72 × Scr mg/dl);
• • Normal liver function: Serum total bilirubin ≤1.5× ULN; Aspartate aminotransferase (AST) ≤2.5× ULN; Alanine aminotransferase (ALT) ≤2.5× ULN;
• • Female patients must have a negative pregnancy test before the study initiation (not applicable to bilateral oophorectomy and/or hysterectomy patients or postmenopausal patients);
• • Signed written informed consent form.
• Exclusion criteria:
• • Receiving anti-tumor therapy prior to enrollment, including but not limited to PD-1 inhibitors, CTLA-4 antibodies, EGFR monoclonal antibodies, EGFR-TKI, and anti-angiogenic drugs;
• • History of autoimmune diseases, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome-associated vascular thrombosis, Wegener's granulomatosis, desiccation syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. (Note: Vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune disease, psoriasis not requiring systemic therapy, or patients not expected to have a relapse without external triggers may be allowed to enroll);
• • Enrolled in another interventional clinical trial within 30 days prior to screening;
• • History of other malignancies (except cured basal cell carcinoma of the skin);
• • Presence of severe, poorly controlled co-morbidities such as heart failure, diabetes mellitus, hypertension, hepatic failure, renal failure, thyroid disease, psychiatric disorders, etc;
• • Known HIV infection or active viral hepatitis or tuberculosis;
• • Major surgery or planned surgery within 30 days prior to the first dose of the investigational drug;
• • Hypersensitivity to the drugs used in the trial or their components;
• • Pregnancy (confirmed by blood or urine HCG test) or breastfeeding women, or subjects of childbearing potential unwilling or unable to use effective contraception until at least 6 months after the last trial treatment;
• • Deemed inappropriate for participation in the study by the investigator.
• • Unwilling or unable to participate in the study or sign the informed consent form.