Clinical trial NCT06024356: Neoadjuvant Chemoradiotherapy Combined With PD-1 Inhibitor and Thymalfasin for Locally Advanced Mid-low Rectal Cancer
Official title: Efficacy and Safety of Neoadjuvant Chemoradiotherapy Combined With PD-1 Inhibitor and Thymalfasin for Locally Advanced Mid-low Rectal Cancer: a Single-center, Retrospective, Controlled Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Colorectal Neoplasms
Keywords: Colorectal Neoplasms
Programmed Cell Death 1 Receptor
Thymalfasin
Neoadjuvant Therapy
Lead sponsor: Beijing Friendship Hospital
Sponsor class: OTHER
First posted: 2023-09-06
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: locally advanced mid-low rectal cancer

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.

Eligibility criteria: 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.

Primary outcomes:
measure: pathologic complete response
timeFrame: 1 year
Secondary outcomes:
measure: neoadjuvant rectal (NAR) score
timeFrame: 1 year
measure: tumor regression grade（TRG）
timeFrame: 1 year
measure: objective response rate (ORR)
timeFrame: 1 year
measure: R0 resection rate
timeFrame: 1 year
measure: anal preservation rate
timeFrame: 1 year
measure: disease free survival (DFS)
timeFrame: 3 year
measure: local recurrence free survival
timeFrame: 3 year
measure: overall survival (OS)
timeFrame: 3 year
Other outcomes:
measure: The expression of CD86
timeFrame: 1 year
measure: The expression of CD163
timeFrame: 1 year
measure: The expression of CD4+
timeFrame: 1 year
measure: The expression of CD8+
timeFrame: 1 year
measure: The expression of PD-1
timeFrame: 1 year
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital medical University
state: Xicheng Dis
Study officials:
References: