Local Ablation Plus Systemic Therapy for Metachronous Liver and/or Lung Oligometastases From Nasopharyngeal Carcinoma

NCT07824856 | Not Yet Recruiting Phase 2

• 1 other identifier: SL-B2025-805-03
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Nasopharyngeal Carcinoma; Neoplasm Metastasis; Lung Metastases; Liver Metastases; Oligometastatic Disease; Ablation Techniques

Keywords

local ablation; thermal ablation; oligometastases; metachronous metastasis; PD-1 inhibitor; gemcitabine; cisplatin; nasopharyngeal carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator

  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).

  From randomization until disease progression or end of study treatment, up to approximately 24 months

Secondary Outcomes (5)

• 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

• 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

• 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

Study Arms (2)

Local ablation plus systemic therapy

EXPERIMENTAL

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.

Procedure: CT-guided percutaneous local ablation; Drug: Gemcitabine; Drug: Cisplatin; Drug: PD-1 inhibitor

Systemic therapy alone

ACTIVE COMPARATOR

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.

Drug: Gemcitabine; Drug: Cisplatin; Drug: PD-1 inhibitor

Interventions

CT-guided percutaneous local ablation PROCEDURE

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.

Local ablation plus systemic therapy

Gemcitabine DRUG

1000 mg/m2 intravenously on days 1 and 8 of each 21-day cycle for 6 cycles.

Local ablation plus systemic therapy; Systemic therapy alone

Cisplatin DRUG

80 mg/m2 intravenously on day 1 of each 21-day cycle for 6 cycles.

Local ablation plus systemic therapy; Systemic therapy alone

PD-1 inhibitor DRUG

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.

Also known as: toripalimab, camrelizumab, tislelizumab, sintilimab

Local ablation plus systemic therapy; Systemic therapy alone

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Related Publications (6)

• 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.

  PMID: 21700408 BACKGROUND

• 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.

  PMID: 35860835 BACKGROUND

• 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.

  PMID: 37207654 BACKGROUND

• 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.

  PMID: 34174189 BACKGROUND

• 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.

  PMID: 38015220 BACKGROUND

• 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.

  PMID: 34341578 BACKGROUND

MeSH Terms

Conditions

Nasopharyngeal Carcinoma; Neoplasm Metastasis

Interventions

Gemcitabine; Cisplatin; Immune Checkpoint Inhibitors; toripalimab; camrelizumab; tislelizumab; sintilimab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Jinhua Huang, MD

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yi-Quan Jiang, MD

CONTACT

+86 20 87343272; jiangyq@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Minimally Invasive Interventional Therapy

Model Details: Participants are randomized 1:1 to local ablation plus systemic therapy or to systemic therapy alone.

Study Record Dates

• First Submitted: September 13, 2026
• First Posted: September 17, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): February 1, 2029
• Last Updated: September 17, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Beginning 6 months and ending 3 years after publication of the primary results.
• Access Criteria: Investigators whose proposed use of the data has been approved by the principal investigator, after signing a data use agreement. Requests should be directed to the principal investigator.

Locations

CN (1)