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
연구 개요
상태
상태
정황
정황
개입 / 치료
개입 / 치료
상세 설명
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.
연구 유형
연구 유형
등록 (추정된)
등록
단계
단계
- 2 단계
연락처 및 위치
연구 연락처
연구 연락처
- 이름: Yi-Quan Jiang, MD
- 전화번호: +86 20 87343272
- 이메일: jiangyq@sysucc.org.cn
연구 장소
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Guangdong
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Guangzhou, Guangdong, 중국, 510060
- Sun Yat-sen University Cancer Center
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연락하다:
- Yi-Quan Jiang, MD
- 전화번호: +86 20 87343272
- 이메일: jiangyq@sysucc.org.cn
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참여기준
자격 기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
팔의 수
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
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실험적: 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.
다른 이름들:
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활성 비교기: 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.
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator
기간: 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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2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Investigator
기간: 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)
기간: 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
기간: 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
기간: 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
기간: 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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공동 작업자 및 조사자
수사관
수사관
- 수석 연구원: Jinhua Huang, MD, Sun Yat-sen University Cancer Center
간행물 및 유용한 링크
일반 간행물
- 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.
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
연구 시작
기본 완료 (추정된)
기본 완료
연구 완료 (추정된)
연구 완료
연구 등록 날짜
최초 제출
최초 제출
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
처음 게시됨
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
- 악구강 질환
- 병리학적 과정
- 부위별 신생물
- 신생물
- 조직학적 유형에 따른 신생물
- 두경부 신생물
- 신생물, 선상 및 상피
- 종양 과정
- 암종
- 이비인후과 질환
- 인두 신생물
- 이비인후과 신생물
- 비인두 질환
- 인두 질환
- 비인두 신생물
- 병리학적 상태, 징후 및 증상
- 비인두암
- 신생물 전이
- 항종양제, 면역학적
- 항종양제
- 약리작용의 분자 메커니즘
- 이종 사이 클릭 화합물, 1- 링
- 이종 사이 클릭 화합물
- 약리학 적 행동
- 화학 작용 및 용도
- 치료 용도
- 무기 화학 물질
- 염소 화합물
- 질소 화합물
- 데 옥시 시티 딘
- 시티 딘
- 피리 미딘 뉴 클레오 시드
- 피리 미딘
- 백금 화합물
- 면역 체크포인트 억제제
- 젬시타빈
- 시스플라틴
- Toripalimab
- Camrelizumab
- 신틸리 맙
- Tislelizumab
기타 연구 ID 번호
기타 연구 ID 번호
- SL-B2025-805-03
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
IPD 공유 기간
IPD 공유 액세스 기준
IPD 공유 지원 정보 유형
- 연구_프로토콜
- 수액
- ICF
- ANALYTIC_CODE
- CSR
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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