Ablation Techniques, Liver Metastases, Lung Metastases, Nasopharyngeal Carcinoma, Neoplasm Metastasis, Oligometastatic Disease
Conditions
Keywords
local ablation, thermal ablation, oligometastases, metachronous metastasis, PD-1 inhibitor, gemcitabine, cisplatin, nasopharyngeal carcinoma
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.
Detailed description
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.
Interventions
PROCEDURECT-guided percutaneous local ablation
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.
DRUGGemcitabine
1000 mg/m2 intravenously on days 1 and 8 of each 21-day cycle for 6 cycles.
DRUGCisplatin
80 mg/m2 intravenously on day 1 of each 21-day cycle for 6 cycles.
DRUGPD-1 inhibitor
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.
Sponsors
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants are randomized 1:1 to local ablation plus systemic therapy or to systemic therapy alone.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Investigator | From randomization to progression or death, up to approximately 28 months | 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. |
| Overall Survival (OS) | From randomization to death from any cause, up to approximately 28 months | 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. |
| 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 | Proportion of participants whose best overall response is CR, PR, or stable disease (SD) per RECIST 1.1. |
| 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 | 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. |
| 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 | Number and proportion of participants with treatment-emergent AEs, serious AEs, and treatment-related AEs, graded per NCI CTCAE v5.0. |
Countries
China
Contacts
CONTACTYi-Quan Jiang, MD
PRINCIPAL_INVESTIGATORJinhua Huang, MD
Sun Yat-Sen University Cancer Center
Outcome results
None listed