A Series of Neoadjuvant Chemoradiotherapy Combined With Immunotherapy for Locally Advanced Rectal Cancer: From a Multicenter Phase II Cohort to a Phase III Randomized Controlled Study

Phase 2

Recruiting

• Conditions: Locally Advanced Rectal Carcinoma
• Interventions: Drug: Tislelizumab

• Registration Number: NCT06312982
• Lead Sponsor: Beijing Friendship Hospital

Brief Summary

The goal of this clinical trial is to compare the efficacy and safety of neoadjuvant chemoradiotherapy combined with tirelizumab compared with neoadjuvant chemoradiotherapy alone for neoadjuvant therapy in patients with locally advanced rectal cancer.

The main questions it aims to answer are:

To evaluate the efficacy and safety of neoadjuvant chemoradiotherapy combined with tirelizumab compared with neoadjuvant chemoradiotherapy alone for neoadjuvant therapy in patients with locally advanced rectal cancer To assess rectal or anal retention as well as quality of life. Participants will receive a long course of NCRT (50 Gy / 25f, capecitabine 850-1000 mg / m2, BID, PO, D1-D5, QW) within the first 5 weeks. In regard to tumor immunotherapy, enrolled patients will receive tislelizumab (200 mg, iv) on the first day at week 2,5, and 8 after initiation of radiotherapy. Thereafter, patients will be treated with two 14-day cycles of the CAPOX（Q 3 w; D1 oxaliplatin, 130mg/m2,iv.gtt; D1-D14, capecitabine, 850-1000mg / m2, BID, PO）regimen. Two CAOPX regimens were treated one week apart.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-02-20
• Status Verified: 2024-03
• Study First Submitted: 2024-03-09
• Study First Submitted QC: 2024-03-09
• Last Update Submitted: 2024-03-09
• Study First Posted: 2024-03-15
• Last Update Posted: 2024-03-15
• Primary Completion: 2026-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 375

Inclusion Criteria

1. Signed a written informed consent form and volunteered to join the study;
2. .Age: 18-75 years old, male or female;
3. Pathohistologically confirmed rectal adenocarcinoma, along with immunohistochemical results of pMMR or genetic test results of MSS;
4. The baseline clinical stage assessed by MRI was T1-2N1-2M0 or T3N0-2M0, MRF (-), lateral lymph nodes (-);
5. The lower tumor margin is 10cm away from the anal margin;
6. Surgical resection;
7. Ability to swallow tablets normally;
8. ECOG PS 0-1；
9. Have not received any anti-tumor treatment for rectal cancer, including radiotherapy, chemotherapy, surgery, etc.;
10. Plan to undergo surgery after the completion of the neoadjuvant therapy;
11. No contraindications to surgery;
12. Main organ function is normal.

Exclusion Criteria

1. Previous history of allergy to monoclonal antibodies, any component of tislelizumab,and capecitabine;

2. Previously has received or is receiving any of the following treatments:

   A)Any tumor-specific surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc; B)Treatment with immunosuppressive drugs or systemic hormones within 2 weeks of first use (dose> 10mg / day prednisone or equivalent dose); inhaled or topical steroids and dose> 10mg / day prednisone or equivalent dose of adrenocorticoid replacement in the absence of active autoimmune disease; C)Having received a live attenuated vaccine within 4 weeks before the first use of the study drug; D)Major surgery or severe trauma within 4 weeks before the first use of study drug;

3. History of any active autoimmune or autoimmune disease, including but not limited to: interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (considered after hormone replacement therapy); patients with psoriasis or asthma / allergy in childhood and adults without any intervention, but patients requiring medical intervention with bronchodilators should not be included;

4. A history of immunodeficiency, including a positive HIV test, or other acquired or congenital immunodeficiency disease, or a history of organ transplantation or allogeneic bone marrow transplantation;

5. Not well controlled cardiac clinical symptoms or disease, including but not limited to: such as (1) grade NYHA II above heart failure, (2) unstable angina, (3) myocardial infarction within 1 year, (4) clinical meaningful supraventricular or ventricular arrhythmia without clinical intervention or clinical intervention still poor control;

6. Severe infection (Grade CTCAE> 2) within 4 weeks prior to the first use of study drug, Such as severe pneumonia, bacteremia, infection complications requiring hospitalization; Baseline chest imaging indicated the presence of active lung inflammation, presence of symptoms and signs and signs of infection within 14 days prior to the first administration of study drug or need for oral or intravenous antibiotics, Except for the preventive use of antibiotics; Found active tuberculosis infection by history or CT, Or those with a history of active tuberculosis infection within 1 year prior to enrollment, Or those with a history of active tuberculosis infection more than 1 year ago but without formal treatment;

7. Presence of active hepatitis B (HBV DNA 2000 IU / mL or 104copies / mL), hepatitis C (positive for hepatitis C antibody, and HCV RNA above the lower limit of detection of the analytical method);

8. A diagnosis of other malignancies within 5 years prior to the first use of study drug, unless a malignancy with low risk of metastasis or death (5-year survival> 90%), such as adequately treated skin basal cell carcinoma or squamous cell carcinoma in situ, are considered;

9. Women in pregnancy or lactation;

10. Other factors, as judged by the investigator, may lead to forced termination of the study, such as other serious illness (including mental illness), alcohol, substance abuse, family or social factors, which may affect the safety or compliance of the subject.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental group	Tislelizumab	The enrolled patients will receive a long course of NCRT (50 Gy / 25f, capecitabine 850-1000 mg / m2, BID, PO, D1-D5, QW) within the first 5 weeks. In regard to tumor immunotherapy, enrolled patients will receive tislelizumab (200 mg, iv) on the first day at week 2,5, and 8 after initiation of radiotherapy. Thereafter, patients will be treated with two 14-day cycles of the CAPOX（Q 3 w; D1 oxaliplatin, 130mg/m2,iv.gtt; D1-D14, capecitabine, 850-1000mg / m2, BID, PO）regimen. Two CAOPX regimens were treated one week apart. Eight to 8-10 weeks after the completion of radiation therapy, patients will undergo multiple examinations, including colonoscopy and MRI. Subsequent treatment options will be determined by each center physician based on their clinical experience.

Primary Outcome Measures

Name	Time	Method
CR	pCR :within 10 days after surgery;cCR :13 weeks after radiotherapy begins	complete response rate=(number of pathological complete responses + number of clinical complete responses)/total number of patients

Secondary Outcome Measures

Name	Time	Method
AE rate	during treatment	Adverse event rate
NAR score	within 10 days after surgery	Neoadjuvant rectal（NAR）score：It is based on the scoring criteria of preoperative treatment
ORR	within 10 days after surgery	objective response rate; objective response rate; objective response rate; objective response rate
OPR	immediately after surgery	organ preservation rate; organ preservation rate; organ preservation rate
immune-related adverse event rate	up to 3 weeks after using tislelizumab	adverse event rate that is deemed to be associated with tislelizumab

Trial Locations

Locations (2)

Beijing Friendship Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

Beijing Friendship Hospital; 🇨🇳 Beijing, Beijing, China