NCT07182565招募中1 期
A Phase Ib/II Study of Hypofractionated Radiotherapy Combined With Immunochemotherapy as Neoadjuvant Treatment for Adenocarcinoma of the Gastroesophageal Junction
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 84
- 试验地点
- 4
- 主要终点
- Safety and tolerability in Phase Ib
研究概览
简要总结
The purpose of this study is to investigate the safety and efficacy of HFRT plus neoadjuvant ICT in locally advanced resectable GEJA.
详细描述
The aim of this study is to investigate whether hypofractionated radiotherapy combined with a PD-1 inhibitor (Serplulimab) and chemotherapy based on the TS regimen is a safe and well-tolerated neoadjuvant strategy for patients with locally advanced resectable gastroesophageal junction adenocarcinoma (GEJA), and whether it can improve the pathological complete response (pCR) rate compared to immunochemotherapy alone.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically and/or cytologically confirmed diagnosis of locally advanced adenocarcinoma of the gastroesophageal junction (GEJ) (Siewert types I-III), defined as cT3-4, any N, M0 or cT2 N+, M0 according to the 8th edition of the AJCC staging system.
- •Determined as resectable locally advanced disease after multidisciplinary team (MDT) evaluation.
- •Age ≥18 years, regardless of sex.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Estimated life expectancy ≥3 months.
- •No prior anti-cancer treatment.
- •At least one measurable lesion as defined by RECIST v1.1 (lesion diameter ≥1 cm on spiral CT or ≥2 cm on standard CT or MRI), assessed within 28 days prior to enrollment.
- •Adequate organ function within 14 days prior to treatment, defined as follows (note: blood transfusions, platelet infusions, or G-CSF use not permitted within 14 days prior to hematologic assessment):
- •1) Hematological: Hemoglobin ≥9 g/dL (without recent transfusion); ANC ≥1.5 × 10⁹/L; WBC ≥3.0 × 10⁹/L (no G-CSF use); Platelets ≥75 × 10⁹/L (no IL-11 or TPO use).
- •2) Biochemistry: Total bilirubin ≤1.5 × ULN; AST and ALT ≤2.5 × ULN; Serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min (Cockcroft-Gault formula); Serum albumin ≥25 g/L.
- •3) Coagulation: INR <1.5, APTT <1.5 × ULN within 7 days before enrollment; PT ≤1.5 × ULN.
- •9.Patients with active hepatitis B or C infection must have received antiviral therapy ≥14 days prior to enrollment, with HBV DNA ≤500 IU/mL or 2500 copies/mL, HCV RNA undetectable, and agree to continue antiviral therapy during the study.
- •10.LVEF ≥50% on echocardiography. 11.Women of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days prior to enrollment and agree to use effective contraception during the study and for at least 3 months after the last dose. Males must use effective contraception during and for at least 3 months after treatment. Female participants must not be breastfeeding or donate/retrieve ova within 60 days after the last dose.
- •12.Willing and able to provide written informed consent and comply with study procedures.
排除标准
- •Confirmed dMMR or MSI-H by immunohistochemistry or genetic testing.
- •Evidence of peritoneal or visceral metastasis (based on thoracoabdominal CT, bone scan, or MRI if bone metastasis is suspected).
- •Other malignancies within the past 5 years, except cured basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
- •Known allergy or hypersensitivity to any study drugs or their excipients; contraindications to study drugs.
- •Clinically significant upper gastrointestinal bleeding within 30 days before enrollment or randomization.
- •Interstitial lung disease, pulmonary fibrosis, active tuberculosis, or steroid-requiring pneumonitis confirmed by CT.
- •Active autoimmune or inflammatory disease requiring immunosuppressants within 2 years (e.g., IBD, SLE, sarcoidosis, Wegener's, MG, Graves', rheumatoid arthritis, etc.); exceptions: well-controlled type 1 diabetes, hypothyroidism under hormone replacement, untreated localized skin diseases (e.g., vitiligo, psoriasis).
- •Immunodeficiency, history of HIV infection or organ transplantation.
- •Active HBV (HBsAg positive) or HCV infection. Previously treated or well-controlled HBV/HCV is allowed.
- •Systemic corticosteroids or immunosuppressants within 2 weeks prior to treatment. Exceptions: inhaled or local steroids, adrenal replacement (<10 mg/day prednisone equivalent), or short-term corticosteroids (<7 days) for prophylaxis or non-autoimmune indications.
- •Uncontrolled comorbidities, including:
- •1）Poorly controlled hypertension (SBP ≥150 mmHg or DBP ≥100 mmHg); 2）Grade II+ myocardial ischemia or MI within 6 months, arrhythmia (QT ≥480 ms, AF), uncontrolled angina, CHF (NYHA III-IV), valvular disease, cardiomyopathy, stroke or TIA history; 3）Active or uncontrolled infection; 4）Liver disease (cirrhosis, decompensation, active hepatitis); 5）Poorly controlled diabetes (FBG >10 mmol/L); 6）Proteinuria ≥++ or 24h urine protein >1.0 g. 12.Coagulation abnormalities (INR >1.5 or APTT >1.5 × ULN), known bleeding tendency, or patients receiving thrombolytic or anticoagulant therapy. Known congenital or acquired bleeding or thrombotic disorders, such as hemophilia, coagulation defects, thrombocytopenia, hypersplenism, etc.
- •Patients with significant hemoptysis (≥2.5 mL per day), or a history of clinically significant bleeding (e.g., gastrointestinal bleeding, hemorrhagic gastric ulcers, or fecal occult blood test ≥++) within 3 months prior to enrollment.
- •Patients requiring long-term anticoagulation with warfarin or heparin, or long-term antiplatelet therapy (aspirin ≥300 mg/day or clopidogrel ≥75 mg/day).
- •13.Major surgery (e.g., craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to first dose, or expected to undergo major surgery during the study, or non-diagnostic surgery within 4 weeks prior to trial initiation.
- •14.History of gastrointestinal perforation and/or fistula within 6 months before enrollment; or history of arterial or venous thromboembolic events, such as stroke (except stable cerebral infarction as judged by the investigator), deep vein thrombosis, or pulmonary embolism.
- •15.Long-term unhealed wounds or fractures. 16.Severe gastrointestinal conditions that may interfere with oral drug absorption, such as inability to swallow, chronic diarrhea, or intestinal obstruction.
- •17.Severe malnutrition. 18.Pregnant or lactating women, or participants of reproductive potential (male or female not postmenopausal for at least one year) who are unwilling to use effective contraception.
- •19.History of substance abuse or uncontrolled psychiatric illness. 20.Unwillingness or inability to comply with study requirements. 21.Participation in another clinical trial within 30 days prior to study entry, or planning to participate in another trial during the study period.
- •22.Any severe or uncontrolled medical condition, judged by the investigator to potentially compromise patient safety or interfere with study completion.
研究组 & 干预措施
Intervention Arm (HFRT+nICT)
Experimental
干预措施: hypofractionated radiotherapy (Radiation)
Intervention Arm (HFRT+nICT)
Experimental
干预措施: PD-1 inhibitor (Drug)
Intervention Arm (HFRT+nICT)
Experimental
干预措施: TS-1 (Drug)
Control Arm (nICT)
Active Comparator
干预措施: PD-1 inhibitor (Drug)
Control Arm (nICT)
Active Comparator
干预措施: TS-1 (Drug)
结局指标
主要结局
Safety and tolerability in Phase Ib
时间窗: within 3 months after the HFRT
Safety will be assessed based on clinical adverse events, vital signs, and abnormalities in laboratory tests during the study period. Adverse events (AEs) will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. All deaths occurring within 90 days after the first dose of treatment or within 30 days after the last dose will be listed along with the causes of death. Laboratory abnormalities will be categorized according to NCI-CTCAE version 5.0. Maximum Tolerated Dose (MTD): If ≥1/3 of patients in a given dose cohort experience radiotherapy-related dose-limiting toxicities (DLTs) within 90 days, that dose level will be considered intolerable. The dose level immediately below will then be defined as the maximum tolerated dose (MTD). At least six evaluable patients are required in the MTD cohort.
pCR rate in Phase II
时间窗: approximately 2 weeks after the resection of primary lesion
pCR rate: The proportion of patients who achieve pathological complete response (pCR), defined as the absence of viable tumor cells on microscopic examination after neoadjuvant therapy.
次要结局
- R0 resection rate(approximately 2 weeks after the resection of primary lesion)
- Objective response rate(From Baseline up to the pre-surgical assessment (performed within 28 days after the last dose of conversion therapy))
- DFS(disease free survival) rate(Up to 3 years)
- OS(overall survival) rate(Up to 3 years)
- Adverse Events (AEs)(From the first dose through 90 days after the last dose)
- Quality of Life (QoL) - EORTC QLQ-C30(Assessments are performed at Baseline, on Day 1 of each subsequent treatment cycle (each cycle is 21 days), at the end-of-treatment visit, and at 1, 3, 6, and 12 months post-surgery during follow-up.)
研究者
Yaqin Zhao
Associate Chief Physician
West China Hospital
研究点 (4)
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