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

Not yet recruiting

• Conditions: Colorectal Neoplasms
• Interventions: Drug: Thymalfasin

• Registration Number: NCT06024356
• Lead Sponsor: Beijing Friendship Hospital

Brief 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.

Detailed Description

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: 26 participants, 13 in each group Study Population: locally advanced mid-low rectal cancer Primary Endpoint: pathologic complete response（pCR） 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.

Study Timeline

• Study First Submitted: 2023-08-08
• Status Verified: 2023-09
• Study First Submitted QC: 2023-09-05
• Last Update Submitted: 2023-09-05
• Study First Posted: 2023-09-06
• Last Update Posted: 2023-09-06
• Study Start: 2023-09-20
• Primary Completion: 2023-12-31
• Study Completion: 2024-03-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 26

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Experimental	Thymalfasin	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.

Primary Outcome Measures

Name	Time	Method
pathologic complete response	1 year	All the enrolled patients will receive total mesorectal excision (TME) 7-9 weeks after the end of long course radiotherapy. The rectal specimens will be evaluated by the pathologists who are experienced on the rectal cancer diagnosis according to the 1997 Dworak grading system. The rectal cancer will be classified into 5 grades. Grade 0-3 will be considered as non-pCR while grade 4 represent pCR.

Secondary Outcome Measures

Name	Time	Method
neoadjuvant rectal (NAR) score	1 year	The neoadjuvant rectal (NAR) score is a promising indicator of survival after preoperative chemoradiotherapy for rectal cancer. The NAR score was calculated according to the following formula: NAR score = \[5pN - 3(cT - pT) + 12\]2⁄9.61.; (clinical tumor (cT) stage, pathologic tumor (pT) stage, pathologic nodal (pN) stage)
R0 resection rate	1 year	During the surgical process, the surgeon will evaluate the level of cancer resection. It will be classified as R0, R1, R2 resection. Therefore, we can calculate R0 resection rate.
tumor regression grade（TRG）	1 year	AJCC 8th TRG classification. TRG 0: No viable cancer cells left in the specimen; complete regression.; TRG 1: Minimal residual cancer cells present; extensive regression with a minimal number of tumor cells.; TRG 2: Moderate residual cancer cells present; substantial regression with a significant number of tumor cells.; TRG 3: Minimal or no regression; no significant tumor cell response to treatment; majority of tumor still present.
anal preservation rate	1 year	the surgeon will decide whether the anal can be preserved on the basis of the rectal cancer and intraoperative situation. anal preservation rate is the percentage of patients who achieve anal preservation.
overall survival (OS)	3 year	During the 3-year follow-up, the percentage of the patients who is sill survival at the end of follow-up.
objective response rate (ORR)	1 year	ORR is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The ORR rate is the sum of complete response (CR) and partial response (PR)
local recurrence free survival	3 year	During the 3-year follow-up, the percentage of local recurrence.
disease free survival (DFS)	3 year	During the 3-year follow-up, the percentage of the patients who is disease free.

Trial Locations

Locations (1)

Beijing Friendship Hospital, Capital medical University; 🇨🇳 Beijing, Xicheng Dis, China