A Prospective Phase II Study of Concurrent Chemoradiotherapy Combined With Toripalimab and Surufatinib in the Treatment of Limited-Stage Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Median progression-free survival (PFS)
研究概览
简要总结
Based on the preclinical rationale for combining surufatinib with immunotherapy, and the clinical efficacy observed with surufatinib in extensive-stage small cell lung cancer (ES-SCLC), the investigators hypothesize that incorporating surufatinib into the ADRIATIC regimen could further enhance survival in LS-SCLC. To evaluate this approach, the investigators plan to conduct a single-arm Phase II study to explore the safety and efficacy of concurrent chemoradiotherapy combined with toripalimab and surufatinib in treating LS-SCLC.
详细描述
This single-arm Phase II study aims to explore the safety and efficacy of concurrent chemoradiotherapy combined with toripalimab and surufatinib in treating LS-SCLC. In this single-arm, Phase II study, patients are planned to receive four cycles of etoposide combined with either cisplatin or carboplatin, along with toripalimab and surufatinib. During chemotherapy, patients will undergo concurrent radiotherapy. Following chemoradiotherapy, consolidation treatment with toripalimab and surufatinib will be administered. Prophylactic cranial irradiation (PCI) is recommended prior to the consolidation therapy.
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
- •Informed Consent: An informed consent form, signed and dated, must be provided before any steps in the study are performed.
- •Age: Males or females aged 18 to 75 years.
- •Diagnosis: Histologically or cytologically confirmed small cell lung cancer (SCLC).
- •Stage: Stage I-III (AJCC/UICC 8th edition TNM staging), where all lesions can be included in a single radical radiotherapy plan (i.e., limited-stage disease). Stage I-II must be inoperable.
- •Life Expectancy: ≥12 weeks.
- •Performance Status (PS): WHO PS score of 0 or
- •Postmenopausal women or those with a negative urine or serum pregnancy test (HCG sensitivity ≥25 IU/L or equivalent) within 7 days before starting study treatment.
- •Female participants must not be breastfeeding.
- •Women of childbearing potential (WOCBP) must agree to use contraception during study treatment and for 3 months after the last dose of study drug (i.e., 30 days for an ovulation cycle plus approximately 5 half-lives of the investigational drug).
- •Male participants engaging in sexual activity with WOCBP must agree to use contraception during study treatment and for 5 months after the last dose of study drug (i.e., 90 days for sperm regeneration cycle plus approximately 5 half-lives of the investigational drug).
- •Males with azoospermia do not need to follow contraception requirements.
- •WOCBP who are not sexually active do not need to follow contraception requirements but must still undergo pregnancy testing as outlined.
- •Organ and Bone Marrow Function:
- •Pulmonary Function: FEV1 ≥800 mL. Absolute neutrophil count ≥1.5 × 10⁹/L. Platelet count ≥100 × 10⁹/L. Hemoglobin ≥9.0 g/dL. Renal Function: Calculated creatinine clearance ≥50 mL/min using the Cockcroft-Gault formula.
- •Serum bilirubin ≤1.5 × upper limit of normal (ULN). AST and ALT ≤2.5 × ULN.
排除标准
- •Participation in Another Clinical Trial: Simultaneous participation in another clinical trial, unless it is an observational (non-interventional) study.
- •Mixed Histology: Histological subtype of mixed small cell and non-small cell lung cancer (SCLC).
- •Extensive-Stage SCLC: Diagnosis of extensive-stage SCLC.
- •Malignant Effusions: Pathologically confirmed malignant pleural effusion or pericardial effusion.
- •Hemoptysis: Central cavitary SCLC with hemoptysis (hemoptysis volume >50 ml/day).
- •Immunosuppressive Treatment: Use of immunosuppressive drugs within 28 days prior to the first dose of toripalimab. Physiological doses of intranasal corticosteroids and systemic corticosteroids ≤10 mg daily of prednisone (or equivalent) are exceptions. Steroids used to manage chemoradiotherapy-related toxicities are allowed.
- •Previous Anti-PD-1/PD-L1 Therapy: Prior use of any anti-PD-1 or anti-PD-L1 antibodies.
- •Major Surgery: Underwent major surgery (excluding vascular access) within 4 weeks before study entry.
- •Autoimmune Disease History: History of autoimmune diseases within the last 2 years, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis.
- •Primary Immunodeficiency: History of primary immunodeficiency.
- •Organ Transplant History: History of organ transplantation requiring immunosuppressive treatment.
- •QT Interval Prolongation: QTc interval (corrected by Bazett's formula) >470 ms, calculated from three ECG measurements.
- •Uncontrolled Comorbidities: Uncontrolled comorbid conditions, including but not limited to persistent or active infections, symptomatic congestive heart failure, poorly controlled hypertension, unstable angina, arrhythmias, active peptic ulcer disease or gastritis, active bleeding disorders, chronic hepatitis C, HIV infection, HBsAg-positive patients with DNA >500 IU/ml, or any psychiatric or social conditions that may interfere with study requirements or the patient's ability to provide informed consent.
- •Tuberculosis History: Known history of tuberculosis.
- •Live Vaccination: Received a live attenuated vaccine within 30 days prior to study initiation.
- •Previous Primary Malignancy: History of another primary malignancy within 5 years prior to study entry, except for adequately treated basal or squamous cell carcinoma of the skin, in situ cervical cancer, ductal carcinoma in situ of the breast, or localized prostate cancer.
- •Pregnancy and Breastfeeding: Pregnant or breastfeeding women, or men and women of reproductive potential who are not using effective contraception.
- •Interference with Study Assessment: Any condition that may interfere with the evaluation of toripalimab's efficacy or safety.
- •Investigator's Discretion: Any other condition that, in the opinion of the investigator, would make the patient unsuitable for participation in the study.
研究组 & 干预措施
The study group
In this single-arm, patients are planned to receive four cycles of etoposide combined with either cisplatin or carboplatin, along with toripalimab and surufatinib. During chemotherapy, patients will undergo concurrent radiotherapy. Following chemoradiotherapy, consolidation treatment with toripalimab and surufatinib will be administered. Prophylactic cranial irradiation (PCI) is recommended prior to the initiation of immunotherapy consolidation.
干预措施: Chemotherapy (Drug)
The study group
In this single-arm, patients are planned to receive four cycles of etoposide combined with either cisplatin or carboplatin, along with toripalimab and surufatinib. During chemotherapy, patients will undergo concurrent radiotherapy. Following chemoradiotherapy, consolidation treatment with toripalimab and surufatinib will be administered. Prophylactic cranial irradiation (PCI) is recommended prior to the initiation of immunotherapy consolidation.
干预措施: Immunotherapy (Drug)
The study group
In this single-arm, patients are planned to receive four cycles of etoposide combined with either cisplatin or carboplatin, along with toripalimab and surufatinib. During chemotherapy, patients will undergo concurrent radiotherapy. Following chemoradiotherapy, consolidation treatment with toripalimab and surufatinib will be administered. Prophylactic cranial irradiation (PCI) is recommended prior to the initiation of immunotherapy consolidation.
干预措施: Angio-immuno kinase inhibitor (Drug)
The study group
In this single-arm, patients are planned to receive four cycles of etoposide combined with either cisplatin or carboplatin, along with toripalimab and surufatinib. During chemotherapy, patients will undergo concurrent radiotherapy. Following chemoradiotherapy, consolidation treatment with toripalimab and surufatinib will be administered. Prophylactic cranial irradiation (PCI) is recommended prior to the initiation of immunotherapy consolidation.
干预措施: radiotherapy (Radiation)
The study group
In this single-arm, patients are planned to receive four cycles of etoposide combined with either cisplatin or carboplatin, along with toripalimab and surufatinib. During chemotherapy, patients will undergo concurrent radiotherapy. Following chemoradiotherapy, consolidation treatment with toripalimab and surufatinib will be administered. Prophylactic cranial irradiation (PCI) is recommended prior to the initiation of immunotherapy consolidation.
干预措施: Prophylactic Cranial Irradiation (Radiation)
The study group
In this single-arm, patients are planned to receive four cycles of etoposide combined with either cisplatin or carboplatin, along with toripalimab and surufatinib. During chemotherapy, patients will undergo concurrent radiotherapy. Following chemoradiotherapy, consolidation treatment with toripalimab and surufatinib will be administered. Prophylactic cranial irradiation (PCI) is recommended prior to the initiation of immunotherapy consolidation.
干预措施: Consolidation Therapy with Toripalimab and Surufatinib (Drug)
结局指标
主要结局
Median progression-free survival (PFS)
时间窗: 2 years
The length of time from the start of treatment until disease progression or death from any cause, whichever occurs first.
次要结局
- Median overall survival (OS)(2 years)
- Treatment-related adverse events(1 year after treatment)
- Patient-Reported Outcomes(1 year after treatment)
研究者
Hui Liu
Professor
Sun Yat-sen University