Neoadjuvant Chemoradiotherapy Combined With PD-1 Inhibitor and Thymalfasin for Locally Advanced Mid-low Rectal Cancer

Registered clinical trial record on ClinicalTrials.gov (NCT06024356). This describes a planned, ongoing, or completed study — it is NOT peer-reviewed results. Status: completed. Study type: observational. Sponsor: Beijing Friendship Hospital. Conditions: Colorectal Neoplasms. Interventions: Thymalfasin. Summary: It is a single-center, retrospective, controlled study to investigate the efficacy and safety of neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and thymalfasin for locally advanced mid-low rectal cancer. Study Purpose 1. To evaluate the efficacy and safety of neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and thymalfasin for locally advanced mid-low rectal cancer. 2. To explore the effects of neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and thymalfasin on the immune microenvironment of locally advanced mid-low rectal cancer. Study Design: A single-center, retrospective, controlled study Subjects were divided into two groups according to whether or not they received thymalfasin: group 1 was treated with neoadjuvant chemoradiotherapy combined with PD-1 inhibitor, and group 2 was treated with neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and thymalfasin. Subjects received long course radiotherapy (50 Gy/25f, 2 Gy/f, 5 days/week) for the first 5 weeks and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day 8) for the first 9 weeks. After that, patients rested for two weeks (week 10-11)。6-8 weeks after the end of radiotherapy, patients underwent TME surgery (12-14 weeks). Thymalfasin was started on the first day of neoadjuvant chemoradiotherapy, 1.6 mg subcutaneously twice a week until the end of the last neoadjuvant treatment. Enrollment: preoperative Tα1 (n=14), postoperative Tα1 (n=7), or no Tα1 (n=26) Study Population: locally advanced mid-low rectal cancer Primary Endpoint: 3-y DFS, pCR rate Exploratory endpoint: Paraffin specimens were collected from biopsies before neoadjuvant therapy and after surgery in patients meeting the inclusion criteria. The expression of CD86, CD163, CD4+T，CD8+T，PD-1 were detected. Primary outcome measures: 3-y DFS; pathologic complete response. Eligibility: Inclusion Criteria: * Patients with rectal adenocarcinoma must satisfied all the following conditions: 1. Stage II/III LARC (cT1-4aN0-2M0); 2. Tumor distal location≤10 cm from anal verge (MRI diagnosed); * Patients regardless of gender with aged≥18 years * ECOG score of 0 or 1 * Physical and viscera function of patients can withstand major abdominal surgery Exclusion Criteria: * Current or previous active malignancy other than rectal cancer； * Patients underwent major surgery within 4 weeks prior to neoadjuvant therapy； * Patients have any condition affects the absorption of capecitabine through gastrointestinal tract； * Patients have severe uncontrolled recurrent infections, or other severe uncontrolled concomitant diseases; * Patients with severe concomitant diseases with estimated survival≤5 years； * Patients with present or previous moderate or severe liver and kidney damage； * Patients preparing for or previously received organ or bone marrow transplant； * Patients who have received immunosuppressive or systemic hormone therapy within 1 month prior to the start of neoadjuvant therapy； * Patients with congenital or acquired immune deficiency (such as HIV infection)； * Pregnant or lactating women.