Clinical trial NCT06312982: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Locally Advanced Rectal Carcinoma
Lead sponsor: Beijing Friendship Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Chao Yang Hospital
name: Peking University Cancer Hospital & Institute
name: CHINA-JAPEN FRIENDSHIP HOSPITAL
name: Peking Union Medical College Hospital
name: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Fudan University
name: Changhai Hospital
name: RenJi Hospital
name: Sir Run Run Shaw Hospital
name: Shandong Provincial Hospital
name: Zhongnan Hospital
name: The First Affiliated Hospital of Zhengzhou University
name: West China Hospital
name: Sichuan Academy of Medical Sciences
name: The Sixth Affiliated Hospital, Sun Yat-sen University
name: The First Hospital of Jilin University
name: First Hospital of China Medical University
name: Army Medical Center of PLA
name: The First Affiliated Hospital of Anhui Medical University
First posted: 2024-03-15
Enrollment: 375
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: CR
timeFrame: pCR :within 10 days after surgery;cCR :13 weeks after radiotherapy begins
Secondary outcomes:
measure: AE rate
timeFrame: during treatment
measure: NAR score
timeFrame: within 10 days after surgery
measure: ORR
timeFrame: within 10 days after surgery
measure: OPR
timeFrame: immediately after surgery
measure: immune-related adverse event rate
timeFrame: up to 3 weeks after using tislelizumab
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital
state: Beijing
Study officials:
References: