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
Overview
- Phase
- Phase 2
- Intervention
- Tislelizumab
- Conditions
- Locally Advanced Rectal Carcinoma
- Sponsor
- Beijing Friendship Hospital
- Enrollment
- 375
- Locations
- 4
- Primary Endpoint
- CR
- Status
- Recruiting
- Last Updated
- 3 months ago
Overview
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.
Investigators
Zhongtao Zhang
The professor
Beijing Friendship Hospital
Eligibility Criteria
Inclusion Criteria
- •Signed a written informed consent form and volunteered to join the study;
- •.Age: 18-75 years old, male or female;
- •Pathohistologically confirmed rectal adenocarcinoma, along with immunohistochemical results of pMMR or genetic test results of MSS;
- •The baseline clinical stage assessed by MRI was T1-2N1-2M0 or T3N0-2M0, MRF (-), lateral lymph nodes (-);
- •The lower tumor margin is 10cm away from the anal margin;
- •Surgical resection;
- •Ability to swallow tablets normally;
- •ECOG PS 0-1；
- •Have not received any anti-tumor treatment for rectal cancer, including radiotherapy, chemotherapy, surgery, etc.;
- •Plan to undergo surgery after the completion of the neoadjuvant therapy;
Exclusion Criteria
- •Previous history of allergy to monoclonal antibodies, any component of tislelizumab,and capecitabine;
- •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;
- •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;
- •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;
- •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;
- •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;
- •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);
- •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;
- •Women in pregnancy or lactation;
Arms & Interventions
Experimental group
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.
Intervention: Tislelizumab
Control group
This group required only 5 weeks of NCRT and 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.
Outcomes
Primary Outcomes
CR
Time Frame: 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 Outcomes
- AE rate(during treatment)
- NAR score(within 10 days after surgery)
- ORR(within 10 days after surgery)
- OPR(immediately after surgery)
- immune-related adverse event rate(up to 3 weeks after using tislelizumab)