Local Ablation Plus Systemic Therapy for Metachronous Liver and/or Lung Oligometastases From Nasopharyngeal Carcinoma
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
研究概览
地位
详细说明
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.
研究类型
注册 (估计的)
阶段
- 阶段2
联系人和位置
学习联系方式
- 姓名:Yi-Quan Jiang, MD
- 电话号码:+86 20 87343272
- 邮箱:jiangyq@sysucc.org.cn
学习地点
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Guangdong
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Guangzhou、Guangdong、中国、510060
- Sun Yat-sen University Cancer Center
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接触:
- Yi-Quan Jiang, MD
- 电话号码:+86 20 87343272
- 邮箱:jiangyq@sysucc.org.cn
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参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
Inclusion Criteria:
- 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)
Exclusion Criteria:
- 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
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的: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.
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Percutaneous thermal ablation of each liver and/or lung metastasis under CT guidance, performed by two interventional radiologists.
The ablation needle is positioned in the center of the lesion and ablation parameters are set according to lesion size and location; ablation ends when the ablation zone covers the entire tumor with a safety margin.
A single lesion is treated in one session; multiple lesions are treated in up to 3 sessions 3-4 weeks apart.
Complete ablation is assessed by contrast-enhanced CT or PET/CT 3-4 weeks after ablation.
Ablation is scheduled at least 3 weeks apart from chemotherapy.
1000 mg/m2 intravenously on days 1 and 8 of each 21-day cycle for 6 cycles.
80 mg/m2 intravenously on day 1 of each 21-day cycle for 6 cycles.
Any PD-1 inhibitor approved by the China NMPA for nasopharyngeal carcinoma, given intravenously at the labeled dose on day 1 of each 21-day cycle: 6 cycles together with chemotherapy, then maintenance every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent, death, or completion of 2 years of treatment.
其他名称:
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有源比较器: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.
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1000 mg/m2 intravenously on days 1 and 8 of each 21-day cycle for 6 cycles.
80 mg/m2 intravenously on day 1 of each 21-day cycle for 6 cycles.
Any PD-1 inhibitor approved by the China NMPA for nasopharyngeal carcinoma, given intravenously at the labeled dose on day 1 of each 21-day cycle: 6 cycles together with chemotherapy, then maintenance every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent, death, or completion of 2 years of treatment.
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator
大体时间:From randomization until disease progression or end of study treatment, up to approximately 24 months
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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).
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From randomization until disease progression or end of study treatment, up to approximately 24 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Investigator
大体时间:From randomization to progression or death, up to approximately 28 months
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Time from randomization to the first documented disease progression per RECIST 1.1 (regardless of treatment continuation) or death from any cause, whichever occurs first.
Participants without an event are censored at the date of the last tumor assessment.
Estimated by the Kaplan-Meier method and compared between arms by log-rank test.
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From randomization to progression or death, up to approximately 28 months
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Overall Survival (OS)
大体时间:From randomization to death from any cause, up to approximately 28 months
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Time from randomization to death from any cause.
Participants alive at the last follow-up are censored at the date last known alive.
Estimated by the Kaplan-Meier method and compared between arms by log-rank test.
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From randomization to death from any cause, up to approximately 28 months
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Disease Control Rate (DCR) Per RECIST 1.1 as Assessed by Investigator
大体时间:From randomization until disease progression or end of study treatment, up to approximately 24 months
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Proportion of participants whose best overall response is CR, PR, or stable disease (SD) per RECIST 1.1.
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From randomization until disease progression or end of study treatment, up to approximately 24 months
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Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator
大体时间:From first documented response to progression or death, up to approximately 28 months
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Among participants with CR or PR, time from the first documented CR or PR to the first documented disease progression per RECIST 1.1 or death from any cause, whichever occurs first.
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From first documented response to progression or death, up to approximately 28 months
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Incidence of Adverse Events (AEs) Per NCI CTCAE Version 5.0
大体时间: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
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Number and proportion of participants with treatment-emergent AEs, serious AEs, and treatment-related AEs, graded per NCI CTCAE v5.0.
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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
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合作者和调查者
调查人员
- 首席研究员:Jinhua Huang, MD、Sun Yat-sen University Cancer Center
出版物和有用的链接
一般刊物
- Yang Y, Qu S, Li J, Hu C, Xu M, Li W, Zhou T, Shen L, Wu H, Lang J, Hu G, Luo Z, Fu Z, Qu S, Feng W, Chen X, Lin S, Zhang W, Li X, Sun Y, Lin Z, Lin Q, Lei F, Long J, Hong J, Huang X, Zeng L, Wang P, He X, Zhang B, Yang Q, Zhang X, Zou J, Fang W, Zhang L. Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2021 Aug;22(8):1162-1174. doi: 10.1016/S1470-2045(21)00302-8. Epub 2021 Jun 23.
- Mai HQ, Chen QY, Chen D, Hu C, Yang K, Wen J, Li J, Shi YR, Jin F, Xu R, Pan J, Qu S, Li P, Hu C, Liu YC, Jiang Y, He X, Wang HM, Lim WT, Liao W, He X, Chen X, Liu Z, Yuan X, Li Q, Lin X, Jing S, Chen Y, Lu Y, Hsieh CY, Yang MH, Yen CJ, Samol J, Feng H, Yao S, Keegan P, Xu RH. Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Nat Med. 2021 Sep;27(9):1536-1543. doi: 10.1038/s41591-021-01444-0. Epub 2021 Aug 2.
- Mai HQ, Chen QY, Chen D, Hu C, Yang K, Wen J, Li J, Shi Y, Jin F, Xu R, Pan J, Qu S, Li P, Hu C, Liu YC, Jiang Y, He X, Wang HM, Lim WT, Liao W, He X, Chen X, Wang S, Yuan X, Li Q, Lin X, Jing S, Chen Y, Lu Y, Hsieh CY, Yang MH, Yen CJ, Samol J, Luo X, Wang X, Tang X, Feng H, Yao S, Keegan P, Xu RH. Toripalimab Plus Chemotherapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: The JUPITER-02 Randomized Clinical Trial. JAMA. 2023 Nov 28;330(20):1961-1970. doi: 10.1001/jama.2023.20181.
- Pan CC, Wu PH, Yu JR, Li W, Huang ZL, Wang JP, Zhao M. Comparative survival analysis in patients with pulmonary metastases from nasopharyngeal carcinoma treated with radiofrequency ablation. Eur J Radiol. 2012 Apr;81(4):e473-7. doi: 10.1016/j.ejrad.2011.05.037. Epub 2011 Jun 23.
- Zhang MX, Liu T, You R, Zou X, Liu YL, Ding X, Duan CY, Xu HS, Liu YP, Jiang R, Wang ZQ, Lin C, Xie YL, Chen SY, Ouyang YF, Xie RQ, Hua YJ, Sun R, Huang PY, Wang SL, Chen MY. Efficacy of local therapy to metastatic foci in nasopharyngeal carcinoma: large-cohort strictly-matched retrospective study. Ther Adv Med Oncol. 2022 Jul 15;14:17588359221112486. doi: 10.1177/17588359221112486. eCollection 2022.
- Yang Y, Pan J, Wang H, Zhao Y, Qu S, Chen N, Chen X, Sun Y, He X, Hu C, Lin L, Yu Q, Wang S, Wang G, Lei F, Wen J, Yang K, Lin Z, Guo Y, Chen S, Huang X, Wu Y, Liang L, Chen C, Bai F, Ma X, Zhang Y, Leaw S, Zhang L, Fang W. Tislelizumab plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer: A multicenter phase 3 trial (RATIONALE-309). Cancer Cell. 2023 Jun 12;41(6):1061-1072.e4. doi: 10.1016/j.ccell.2023.04.014. Epub 2023 May 18.
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
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其他研究编号
- SL-B2025-805-03
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IPD 计划说明
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IPD 共享支持信息类型
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