- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT07824856
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
Aperçu de l'étude
Statut
Les conditions
Description détaillée
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.
Type d'étude
Inscription (Estimé)
Phase
- Phase 2
Contacts et emplacements
Coordonnées de l'étude
- Nom: Yi-Quan Jiang, MD
- Numéro de téléphone: +86 20 87343272
- E-mail: jiangyq@sysucc.org.cn
Lieux d'étude
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Guangdong
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Guangzhou, Guangdong, Chine, 510060
- Sun Yat-sen University Cancer Center
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Contact:
- Yi-Quan Jiang, MD
- Numéro de téléphone: +86 20 87343272
- E-mail: jiangyq@sysucc.org.cn
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: 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.
Autres noms:
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Comparateur actif: 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.
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator
Délai: 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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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Investigator
Délai: 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)
Délai: 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
Délai: 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
Délai: 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
Délai: 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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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Jinhua Huang, MD, Sun Yat-sen University Cancer Center
Publications et liens utiles
Publications générales
- 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.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies stomatognathiques
- Processus pathologiques
- Tumeurs par site
- Tumeurs
- Tumeurs par type histologique
- Tumeurs de la tête et du cou
- Tumeurs, glandulaires et épithéliales
- Processus néoplasiques
- Carcinome
- Maladies oto-rhino-laryngologiques
- Tumeurs pharyngées
- Tumeurs oto-rhino-laryngologiques
- Maladies nasopharyngées
- Maladies pharyngées
- Tumeurs du nasopharynx
- Conditions pathologiques, signes et symptômes
- Carcinome du nasopharynx
- Métastase néoplasmique
- Agents antinéoplasiques immunologiques
- Agents antinéoplasiques
- Mécanismes moléculaires d'action pharmacologique
- Composés hétérocycliques, 1 anneau
- Composés hétérocycliques
- Actions pharmacologiques
- Actions et utilisations chimiques
- Utilisations thérapeutiques
- Produits chimiques inorganiques
- Composés de chlore
- Composés d'azote
- Désoxycytidine
- Cytidine
- Nucléosides pyrimidine
- Pyrimidines
- Composés en platine
- Inhibiteurs de point de contrôle immunitaire
- Gemcitabine
- Cisplatine
- toripalimab
- camrélizumab
- sinttilimab
- tislelizumab
Autres numéros d'identification d'étude
- SL-B2025-805-03
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Description du régime IPD
Délai de partage IPD
Critères d'accès au partage IPD
Type d'informations de prise en charge du partage d'IPD
- PROTOCOLE D'ÉTUDE
- SÈVE
- CIF
- ANALYTIC_CODE
- RSE
Informations sur les médicaments et les dispositifs, documents d'étude
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