Short-term radiotherapy followed by chemotherapy for advanced rectal cancer

A Multicenter, Single-arm, Open-label Clinical Trial of Short-Course Radiotherapy Followed by Neoadjuvant Chemotherapy, HLX07 and Serplulimab in the Treatment for RAS/BRAF Wild Type Locally Advanced Rectal Cancer

This study is testing a new treatment plan that combines short-term radiation and chemotherapy to see if it helps people with advanced rectal cancer have no remaining tumor cells after surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 29 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (Academic / other)
• Drugs / interventions: chemotherapy, prednisone, Serplulimab
• Locations: 3 sites (Wuhan, Hubei and 2 other locations)
• Trial ID: NCT06542588 on ClinicalTrials.gov

What this trial studies

This multicenter, open-label phase II clinical study aims to evaluate the complete response rate in patients with RAS/BRAF wild type locally advanced rectal cancer (LARC) treated with a combination of short-term radiotherapy, HLX07, Serplulimab, and CAPOX. The study includes 29 patients and focuses on assessing both pathological and clinical complete responses through various evaluation methods, including digital rectal examination and MRI. The primary endpoint is the complete response rate, defined as the absence of viable tumor cells in resected specimens and lymph nodes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with histologically confirmed locally advanced rectal adenocarcinoma and specific genetic profiles.

Not a fit: Patients with prior anti-tumor therapies or those with contraindications for surgery may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with locally advanced rectal cancer.

How similar studies have performed: While this study employs a novel combination of therapies, similar approaches have shown promise in other trials targeting rectal cancer.

Eligibility criteria

Inclusion Criteria:

1. Patients or their family members agree to participate in the study and sign the informed consent form;
2. Age 18-75 years, male or female;
3. Histologically confirmed Locally Advanced rectal adenocarcinoma
4. Genetic test and/or immunohistochemical confirmation of RAS, BRAF wild type
5. inferior margin ≤ 10 cm from the anal verge;
6. Pelvic MRI shows high risk \[meets one of the following conditions\]:

   * Clinical tumor (cT) staging cT4a or cT4b (according to AJCC 8th Edition)
   * Extramural vascular infiltration
   * Clinical lymph node (cN) staging cN2 (according to AJCC 8th Edition)
   * Mesenteric fascia is involved
   * Lateral lymph node enlargement 7 ECOG performance status score is 0-1;

8\. Swallowing pills normally; 9. Untreated with anti-tumor therapy for rectal cancer, including radiotherapy, chemotherapy, surgery, etc; 10. There was no operative contraindication; 11. Laboratory tests were required to meet the following requirements: white blood cell (WBC) ≥ 4×109/L; Absolute neutrophil count (ANC) ≥ 1.5×109/L; Platelet count ≥ 100×109/L; Hemoglobin ≥90 g/L; Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN); Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; Serum creatinine ≤1.5 times the upper limit of normal value or creatinine clearance rate ≥50 mL/min; International normalized ratio (INR) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN 12. Males or females with reproductive ability who are willing to use contraception in the trial;

Exclusion Criteria:

1. Documented history of allergy to study drugs, including any component of Anti-EGFR or PD-1 antibody, capecitabine, oxaliplatin and other platinum drugs;
2. Have received or are receiving any of the following treatments:

   Any radiotherapy, chemotherapy or other anti-tumor drugs for tumor; Patients who need to be treated with corticosteroid (dose equivalent to prednisone of \>10 mg/day) or other immunosuppressive agents within 2 weeks prior to study drug administration; Received live attenuated vaccine within 4 weeks before the first use of the study drug; Major surgery or severe trauma within 4 weeks before the first use of the study drug;
3. Any active autoimmune disease or history of autoimmune disease;
4. Have a history of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation or allogeneic bone marrow transplantation;
5. There are clinical symptoms or diseases of heart that are not well controlled;
6. Severe infection (CTCAE \> 2) occurred within 4 weeks before the first use of the study drug; Baseline chest imaging revealed active pulmonary inflammation, signs and symptoms of infection within 14 days prior to the first use of the study drug, or oral or intravenous antibiotic therapy, except for prophylactic use of antibiotics;
7. Patients with active pulmonary tuberculosis infection found by medical history or CT examination, or with a history of active pulmonary tuberculosis infection within one year before enrollment, or with a history of active pulmonary tuberculosis infection more than one year ago but without regular treatment;
8. The presence of active hepatitis B (HBV DNA \> 2000 IU/mL or 104 copies/mL) was positive for hepatitis C (hepatitis C antibody) and HCV RNA was higher than the lower limit of analytical method;
9. Female subject who is pregnant or breastfeeding;
10. Patients who are not suitable for participation in clinical trials in the opinion of the investigator

Where this trial is running

Wuhan, Hubei and 2 other locations

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

Study contacts

• Principal investigator: Zhenyu Lin, MD — Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
• Study coordinator: zhenyu Lin, MD

Conditions Rectal Cancer