A Phase II Study of Total Neoadjuvant Chmoradiation Treatment Plus SHR1210 for High-risk Locally Advanced Rectal Cancer and Biomarker Screening Base on Neoantigen

Peking University Cancer Hospital & Institute1 个研究点分布在 1 个国家目标入组 25 人开始时间: 2020年5月25日最近更新: 2020年7月9日

适应症

干预措施

试验速览

阶段: 2 期
发起方
入组人数: 25
试验地点: 1
主要终点: pathologic complete response rate(pCR rate)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This study is designed to test the efficacy and safety of Total Neoadjuvant Treatment plus SHR1210（an anti-PD-1 Inhibitor) for High-risk locally advanced Rectal Cancer, Meanwhile, screening effective Biomarker base on neoantigen.

详细描述

The combined treatment model of neoadjuvant chemoradiotherapy treatment + radical rectal resection + adjuvant therapy has become the standard treatment model for locally advanced mid-low rectal cancer, However, the existing evidence shows that this comprehensive treatment method has reached the upper limit of efficacy and cannot continue to reduce the metastatic rate and improve the survival rate.

Recent studies have shown that PD-1 antibody inhibitors have excellent curative effects on the treatment of a variety of tumors and have good safety.

This study is a single-arm, single-center, prospective, phase II clinical study. It is designed to test the efficacy and safety of Total Neoadjuvant chmoradiation Treatment plus SHR1210 for High-risk locally advanced Rectal Cancer, Meanwhile, screening effective Biomarker base on neoantigen.

In this study, patients with high-risk rectal cancer will receive 3 cycles induction CapeOX and SHR-1210, intensity modulated radiotherapy with concurrent capecitabine and 2 cycles consolidation CapeOX and total mesorectal excision.

This study is designed to recruit 25 patients in all.

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 70 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Age ≥ 18 years and ≤70 years.
•ECOG Performance status 0-
•Histologically confirmed diagnosis of adenocarcinoma of the rectum.
•The distance from down verge of tumor to anal-rectal junction (ARJ) ≤8cm, or ≤12 cm based on sigmoidoscopy.
•Clinical Stage T3c, T3d, T4a or T4b, or EMVI (+) or mrN2 or MRF (+) based on MRI.
•No evidence of distant metastases.
•No prior pelvic radiation therapy.
•No prior chemotherapy or surgery for rectal cancer.
•No active infections requiring systemic antibiotic treatment.
•No systemic infection requiring antibiotic treatment.
•No immune system disease.
•ANC > 1.5 cells/mm3, HGB > 9.0 g/dL, PLT > 100,000/mm3, total bilirubin≤ 1.5×ULN, AST≤ 2.5×ULN, ALT ≤ 2.5×ULN.
•Serum creatinine is within 1.5 times the physiological range， creatinine clearance rate≥50 ml/min
•Patients with controllable hypertension were included.
•Patients who did not receive anticoagulant therapy: INR, aPTT is required to be within the 1.5 times the physiological range;Patients who receive anticoagulant therapy: INR, aPTT is required to be within the physiological range.
•FT3, FT4, TSH are Normal or abnormal without clinical significance.
•ECG examination is Normal or abnormal without clinical significance; Echocardiography shows that LVEF>50%.
•Patients must read, agree to, and sign a statement of Informed Consent prior to participation in this study.
•Patients show good adherence, follow -up on time. It is recommended that all patients provide tumor tissue samples (preferably fresh tissue samples) for pathological genetic testing prior to enrollment.
•Fertile men or women with potential for pregnancy must use highly effective contraception throughout the trial. And continue contraception for 12 months after treatment ends.

排除标准

•Recurrent rectal cancer.
•Anticipated unresectable tumor after neoadjuvant treatment.
•Patients with a history of a prior malignancy within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer.
•Patients with a history of any arterial thrombotic event within the past 6 months. This includes angina (stable or unstable), MI, TIA, or CVA.
•Other Anticancer or Experimental Therapy.
•Women who are pregnant or breast-feeding.
•Patients with any other concurrent medical or psychiatric condition or disease which would make them inappropriate candidates for entry into this study.
•Patients with a history of anti-PD-1, anti-PD-L1, anti-PD-L2 or CEGFR TKI therapy.
•Patients underwent major surgery or had not recovered from the side effects of this surgery, received a vaccine, received immunotherapy within 4 weeks before the first use of the study drug, and received radiotherapy within 2 weeks.
•Patients who received hematopoietic stimulating factors therapy, such as G-CSF and erythropoietin, within 1 week before the first administration of the study drug.
•Patients are allergic to study medication and its ingredients.
•Patients have active lung disease (such as interstitial pneumonia, pneumonia, obstructive pulmonary disease, asthma) or active tuberculosis.
•Patients have any uncontrollable clinical problems, including but not limited to:
•Persistent or severe infection.
•Hypertension that can't be effectively controlled by drugs（ blood pressure reading of 150 over 90）.
•Uncontrolled diabetes
•Heart disease (Class III / IV congestive heart failure or cardiac block as defined by the New York Heart Association)
•Patient has or is suspected of having an autoimmune disease,Such as pituitary inflammation, colitis, hepatitis, nephritis, hyperthyroidism, hypothyroidism, etc.
•Patients have other serious, acute or chronic diseases or have abnormal test results, and the investigator judges that this may increase the patient's risk of participating in the trial or interfere with the results.

研究组 & 干预措施

TNT+SHR1210

Experimental

Patients with high-risk locally advanced rectal cancer will receive chemotherapy and SHR-1210 before chemoradiaton, after chemoradiaton, patient will receive consolidation chemotherapy. This arm is called Total Neoadjuvant Treatment (TNT) plus SHR-1210. The neoadjuvant chemotherapy regimen is designed as 3 cycles of CapeOX ( Capecitabine + Oxaliplatin ) plus SHR-1210 over a period of approximately 8 weeks. Tumor response will be evaluated after chemotherapy. Then patients will undergo 22f-IMRT (Intensity modulated radiotherapy) with capecitabine. Patients will receive two more cycles of consolidation CapeOX if tolerable when there was no progressed disease in induction CapeOX.