Combining pembrolizumab with bevacizumab and CapeOX for treating advanced colorectal cancer

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

This study is testing a new combination of treatments for people with advanced colorectal cancer to see if it helps shrink the tumors before surgery.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Xijing Hospital (other)
• Drugs / interventions: pembrolizumab, bevacizumab
• Locations: 1 site (Xi'an, Shaanxi)
• Trial ID: NCT06550453 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and efficacy of pembrolizumab in combination with bevacizumab and CapeOX as a neoadjuvant treatment for patients with locally advanced colorectal cancer that is RAS-mutated and BRAF wild-type. The study will enroll 20 patients and is designed in two phases, where the first phase will assess initial responses, and if successful, the second phase will further evaluate the treatment's effectiveness. Patients will receive 2-4 cycles of the combined therapy, with the primary goal of achieving a pathological complete response (pCR).

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with RAS-mutated, BRAF wild-type, microsatellite-stabilized locally advanced colorectal cancer who have not received prior treatment.

Not a fit: Patients with colorectal cancer that is not RAS-mutated or BRAF wild-type, or those with microsatellite instability may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with a specific type of advanced colorectal cancer.

How similar studies have performed: Other studies have shown promising results with similar combinations of immunotherapy and chemotherapy in treating advanced colorectal cancer.

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.

Where this trial is running

Xi'an, Shaanxi

• the First Affliated Hospital (Xijing Hospital),the First Affiliated Hospital of Air Force Military Medical University — Xi'an, Shaanxi, China (RECRUITING)

Study contacts

• Study coordinator: Jianjun Yang, Professor

Conditions: Locally Advanced Colorectal Cancer, Locally advanced colorectal cancer, pembrolizumab, microsatellite-stabilized, CapeOX neoadjuvant