Efficacy and Safety of Local Ablation Combined With Systemic Therapy for Metachronous Hepatic and/or Pulmonary Oligometastases From Nasopharyngeal Carcinoma: A Single-Center, Open-Label, Randomized Controlled Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 138
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator
研究概览
简要总结
This single-center, open-label, randomized phase II trial evaluates whether CT-guided local ablation of liver and/or lung oligometastases, added to systemic therapy, improves the objective response rate compared with systemic therapy alone in patients with metachronous liver and/or lung oligometastases (no more than 5 lesions, each 3 cm or smaller) from nasopharyngeal carcinoma.
详细描述
Metachronous metastasis is defined as distant metastasis detected at least 6 months after curative treatment of the primary nasopharyngeal tumor. Eligible participants are randomized 1:1 to local ablation plus systemic therapy or systemic therapy alone.
Ablation is performed under CT guidance by two interventional radiologists; multiple lesions are treated in up to 3 sessions 3-4 weeks apart, and complete ablation is assessed by contrast-enhanced CT or PET/CT 3-4 weeks after ablation.
Systemic therapy in both arms consists of gemcitabine 1000 mg/m2 on days 1 and 8 plus cisplatin 80 mg/m2 on day 1 with a PD-1 inhibitor on day 1 every 3 weeks for 6 cycles, followed by PD-1 inhibitor maintenance every 3 weeks for up to 2 years. Tumor response is assessed per RECIST 1.1 every 8 weeks. Adverse events are graded per NCI CTCAE v5.0.
The sample size of 138 (69 per arm) provides 80% power at a two-sided alpha of 0.05 to detect an improvement in objective response rate from 70% to 90%, allowing for 10% dropout.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent to participate in the trial
- •Age 18 to 75 years, any sex
- •Histologically or cytologically confirmed nasopharyngeal carcinoma, with clinically diagnosed liver and/or lung metastases
- •Primary nasopharyngeal tumor cured after curative treatment, with no lymph node metastasis and no metastases outside the liver and lung (metachronous metastasis: distant metastasis detected at least 6 months after curative treatment of the primary tumor)
- •No more than 5 liver and/or lung metastases, each 3 cm or smaller in diameter
- •Liver and/or lung metastases amenable to ablation
- •ECOG performance status 0 or 1
- •Adequate hematologic and organ function: absolute neutrophil count ≥1.5×10^9/L; hemoglobin ≥70 g/L; platelet count ≥50×10^9/L; white blood cell count ≥3.0×10^9/L; serum albumin ≥28 g/L; total bilirubin ≤3.0 mg/dL; AST and ALT ≤5×ULN; serum creatinine ≤1.5×ULN; INR ≤2.3 (without anticoagulant therapy)
- •No prior systemic therapy for metastatic disease (e.g., gemcitabine plus cisplatin chemotherapy or PD-1 inhibitor)
排除标准
- •History of hypersensitivity or intolerance to any study drug
- •Severe hepatic insufficiency, pulmonary fibrosis, or pulmonary hypertension
- •Poorly controlled infectious or radiation-induced inflammation around the lesion, skin infection at the puncture site, systemic infection, or fever >38.5 °C
- •Estimated life expectancy less than 3 months
- •Poorly controlled malignant pleural effusion
- •Clinically significant bleeding within 30 days before study entry
- •Uncorrectable coagulopathy or marked hematologic abnormality with evident bleeding tendency
- •Severe hepatic, renal, cardiac, pulmonary, or cerebral dysfunction; severe anemia, dehydration, or nutritional/metabolic disturbance that cannot be corrected in the short term; left ventricular ejection fraction <45%
- •History of congenital long QT syndrome, or corrected QT interval >480 ms (Fridericia)
- •Psychiatric disorder in an active episode
- •Poorly controlled hypertension: systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg
- •Urine protein ≥1 g/24 h (participants with ≥1+ proteinuria on dipstick must have 24-hour urine protein measured); prior organ transplantation
- •Anticoagulant and/or antiplatelet therapy (except novel oral anticoagulants such as dabigatran and rivaroxaban) not discontinued for more than 5-7 days before ablation
- •Other malignancy within the previous 3 years or concurrently
- •Prior gemcitabine plus cisplatin chemotherapy or PD-1 inhibitor therapy
- •Any other condition that, in the investigator's judgment, makes the patient unsuitable for the trial
研究组 & 干预措施
Local ablation plus systemic therapy
CT-guided percutaneous local ablation of all liver and/or lung oligometastases (single lesion in one session; multiple lesions in up to 3 sessions, 3-4 weeks apart), followed by gemcitabine plus cisplatin with a PD-1 inhibitor every 3 weeks for 6 cycles, then PD-1 inhibitor maintenance every 3 weeks for up to 2 years.
干预措施: CT-guided percutaneous local ablation (Procedure)
Local ablation plus systemic therapy
CT-guided percutaneous local ablation of all liver and/or lung oligometastases (single lesion in one session; multiple lesions in up to 3 sessions, 3-4 weeks apart), followed by gemcitabine plus cisplatin with a PD-1 inhibitor every 3 weeks for 6 cycles, then PD-1 inhibitor maintenance every 3 weeks for up to 2 years.
干预措施: PD-1 inhibitor (Drug)
Systemic therapy alone
Gemcitabine plus cisplatin with a PD-1 inhibitor every 3 weeks for 6 cycles, then PD-1 inhibitor maintenance every 3 weeks for up to 2 years.
干预措施: PD-1 inhibitor (Drug)
Systemic therapy alone
Gemcitabine plus cisplatin with a PD-1 inhibitor every 3 weeks for 6 cycles, then PD-1 inhibitor maintenance every 3 weeks for up to 2 years.
干预措施: Gemcitabine (Drug)
Local ablation plus systemic therapy
CT-guided percutaneous local ablation of all liver and/or lung oligometastases (single lesion in one session; multiple lesions in up to 3 sessions, 3-4 weeks apart), followed by gemcitabine plus cisplatin with a PD-1 inhibitor every 3 weeks for 6 cycles, then PD-1 inhibitor maintenance every 3 weeks for up to 2 years.
干预措施: Gemcitabine (Drug)
Local ablation plus systemic therapy
CT-guided percutaneous local ablation of all liver and/or lung oligometastases (single lesion in one session; multiple lesions in up to 3 sessions, 3-4 weeks apart), followed by gemcitabine plus cisplatin with a PD-1 inhibitor every 3 weeks for 6 cycles, then PD-1 inhibitor maintenance every 3 weeks for up to 2 years.
干预措施: Cisplatin (Drug)
Systemic therapy alone
Gemcitabine plus cisplatin with a PD-1 inhibitor every 3 weeks for 6 cycles, then PD-1 inhibitor maintenance every 3 weeks for up to 2 years.
干预措施: Cisplatin (Drug)
结局指标
主要结局
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator
时间窗: From randomization until disease progression or end of study treatment, up to approximately 24 months
Proportion of participants whose best overall response is complete response (CR) or partial response (PR) per RECIST 1.1. Tumor assessment (CT/MRI or PET/CT) is performed at baseline, after the first ablation, and every 8 weeks (±7 days) thereafter until disease progression, regardless of treatment continuation, and is evaluated by the investigator and by a senior radiologist. Analyzed in the full analysis set (all randomized participants, intention-to-treat).
次要结局
- Incidence of Adverse Events (AEs) Per NCI CTCAE Version 5.0(From first study treatment until 30 days after the last dose of study treatment (or start of new anticancer therapy, whichever first), up to approximately 25 months)
- Disease Control Rate (DCR) Per RECIST 1.1 as Assessed by Investigator(From randomization until disease progression or end of study treatment, up to approximately 24 months)
- Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator(From first documented response to progression or death, up to approximately 28 months)
- Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Investigator(From randomization to progression or death, up to approximately 28 months)
- Overall Survival (OS)(From randomization to death from any cause, up to approximately 28 months)
研究者
Huang Jinhua
Professor, Department of Minimally Invasive Interventional Therapy
Sun Yat-sen University