A Phase II Clinical Study of Long-Course Concurrent Chemoradiotherapy Combined With Adebrelimab and Apatinib as Neoadjuvant Therapy for Locally Advanced/Low-Lying Rectal Cancer With Sphincter-Preservation Demand
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Complete Response Rate (cCR+pCR)
研究概览
简要总结
To observe and evaluate the efficacy and safety of neoadjuvant long-course concurrent chemoradiotherapy combined with Adebrelimab and Apatinib Mesylate in the treatment of locally advanced rectal cancer and low-lying rectal cancer with sphincter-preservation demand.
详细描述
The pathological complete response (pCR) rate of standard neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC) is only 10%-15%, and patients with low-lying rectal cancer face difficulties in sphincter preservation, with their quality of life severely compromised. Immune checkpoint inhibitors combined with chemoradiotherapy have demonstrated potential to improve pCR rates, with the NECTAR study reporting a pCR rate of 40% and the VOLTAGE-A study showing a pCR rate of 30% in MSS patients. Anti-angiogenic agents can reverse the immunosuppressive tumor microenvironment and exert synergistic antitumor effects when combined with chemoradiotherapy and immunotherapy. Based on the above background, this study is a single-center, single-arm phase II clinical trial designed to enroll 43 patients with locally advanced rectal cancer and low-lying rectal cancer with sphincter-preservation demand, to explore the efficacy and safety of neoadjuvant long-course concurrent chemoradiotherapy (45-50 Gy/25 fractions, concurrent capecitabine) combined with Adebrelimab (an anti-PD-L1 monoclonal antibody) and Apatinib Mesylate (an anti-angiogenic TKI). This study aims to provide rectal cancer patients with novel therapeutic strategies offering higher remission rates and greater opportunities for sphincter preservation.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 18 to 75 years, male or female;
- •Histologically or cytologically confirmed rectal cancer with measurable tumor lesion(s) (spiral CT or MRI scan ≥10 mm, meeting RECIST 1.1 criteria);
- •Clinical stage: rectal cancer cT3-4N0M0 or cT1-4N+M0, and low rectal cancer with a sphincter-preservation requirement (distance from the anal verge <5 cm; stage T2N0M0);
- •Expected survival >3 months;
- •ECOG PS score: 0-1;
- •No peritoneal metastasis or other distant metastasis;
- •No prior radiotherapy or immune checkpoint inhibitor therapy for rectal cancer;
- •Adequate function of vital organs as required (without the use of any blood components or cell growth factors during screening):
- •Absolute neutrophil count ≥1.5×10⁹/L; platelet count ≥80×10⁹/L; hemoglobin ≥8.5 g/dL; Thyroid-stimulating hormone (TSH) ≤1×ULN (if abnormal, T3 and T4 levels should also be assessed; patients with normal T3 and T4 levels may be enrolled); Bilirubin ≤1.5×ULN; ALT and AST ≤2.5×ULN; Serum creatinine ≤1.5×ULN;
- •Women of childbearing potential must have a negative pregnancy test (β-HCG) before starting treatment. Women of childbearing potential and men (who are sexually active with women of childbearing potential) must agree to use effective contraception consistently during treatment and for 6 months after the last dose;
- •Subjects voluntarily participate in the study and sign the informed consent form.
排除标准
- •Prior pelvic or abdominal radiotherapy;
- •Tumor expected to be unresectable after neoadjuvant therapy;
- •Pregnant or breastfeeding women, or women/ men of childbearing potential who refuse to use contraceptive measures;
- •History of other malignancies within the past 5 years, except for adequately treated cervical carcinoma in situ or cutaneous squamous cell carcinoma, or well-controlled basal cell carcinoma of the skin;
- •Uncontrolled symptomatic brain metastases, or poorly controlled psychiatric disorders, or severe intellectual or cognitive impairment;
- •Pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, or severely impaired pulmonary function;
- •Active, known, or suspected autoimmune disease. Subjects with stable conditions not requiring systemic immunosuppressive therapy are eligible, e.g., type 1 diabetes, hypothyroidism requiring hormone replacement therapy, and skin conditions not requiring systemic treatment (e.g., vitiligo, psoriasis, and alopecia);
- •Congestive heart failure, uncontrolled arrhythmia, myocardial infarction within 6 months, unstable angina, stroke or transient ischemic attack, severe hypertension refractory to medication, or other conditions rendering the patient unable to tolerate surgery;
- •Severe active infection requiring intravenous antibiotic therapy during the screening period;
- •Known allergy to the study drug or any of its excipients, or a history of severe allergic reaction to other monoclonal antibodies;
- •Clinically significant bleeding symptoms or a clear bleeding tendency within 3 months prior to enrollment;
- •Hypertension that remains uncontrolled despite antihypertensive therapy prior to enrollment;
- •Patients with dysphagia;
- •Receipt of or planned receipt of live vaccines within 30 days prior to administration of adebrelimab;
- •Known history of HIV infection, or active hepatitis B or hepatitis C;
- •Inability to comply with the study protocol or to cooperate with follow-up;
- •Other conditions that the investigator considers inappropriate for participation in this trial.
结局指标
主要结局
Complete Response Rate (cCR+pCR)
时间窗: cCR assessed after neoadjuvant therapy; pCR assessed within 2 weeks post-surgery; assessed up to 6 months.
Proportion of patients achieving clinical complete response (cCR, no tumor residue by imaging and endoscopy) after neoadjuvant therapy or pathological complete response (pCR, no residual viable tumor cells in the tumor bed, %RVT=0) post-surgery.
次要结局
- Objective Response Rate (ORR)(Imaging assessment after every 2 cycles（21 days per cycle） of treatment and post-surgery; assessed up to 6 months.)
- Pathological Complete Response (pCR)(Assessed via pathological examination of surgical specimens within 2 weeks post-surgery; assessed up to 6 months.)
- Tumor Regression Grade (TRG):(Assessed via pathological examination of surgical specimens within 2 weeks post-surgery; assessed up to 6 months.)
- Sphincter Preservation Rate(Assessed within 2 weeks post-surgery; assessed up to 6 months.)
- Disease-Free Survival (DFS)(Time from first treatment to recurrence or death (whichever occurs first), assessed up to 36 months.)
- Overall Survival (OS)(Time from first treatment to death from any cause, assessed up to 36 months.)
- Adverse Event Rate(Continuous monitoring from informed consent to 90 days after the last dose; assessed up to 36 months.)
- Quality of Life (EORTC QLQ-CR29)(Assessed at baseline, pre-surgery post-neoadjuvant therapy, and at 3, 6, and 12 months post-surgery (5 time points in total); assessed up to 12 months.)
- Anal Function (LARS Score)(Assessed at baseline, pre-surgery post-neoadjuvant therapy, and at 3, 6, and 12 months post-surgery (5 time points in total);assessed up to 12 months.)
- Biomarker Exploration(Baseline tumor tissue and peripheral blood collected. Peripheral blood sampled 3 times during treatment (pre-RT, post-RT, and pre-surgery); tissue collected once at baseline only. Assessed up to 6 months.)
研究者
Chunbo Zhao
Chief Physician
Harbin Medical University