Surgery vs. Watch-and-Wait Strategy in Complete Responders for Hepatocellular Carcinoma (SWITCH)

Официальное название

Surgery Versus Maintenance After Conversion-therapy-Achieved Complete/Partial Response in Hepatocellular Carcinoma: a Prospective Multicenter Non-randomized Cohort Study

Обзор

The "Surgery versus Maintenance after Conversion-therapy-achieved Complete/Partial Response in Hepatocellular Carcinoma (SWITCH)" study is a multicenter, open-label, prospective non-randomized cohort study with the protocol number SWITCH-01 (Version 0.1, dated October 5, 2025). Sponsored by West China Hospital of Sichuan University and led by Principal Investigator Wu Hong, the study involves 10 participating centers and has completed NCT registration. Its core objective is to evaluate and compare the efficacy and safety of two management strategies-surgical resection and maintenance therapy-in patients with hepatocellular carcinoma (HCC) who have achieved complete response (CR) or partial response (PR) after conversion therapy and are deemed eligible for curative liver resection (R0) by a multidisciplinary team (MDT). The study is designed to address the clinical dilemma of optimal management for initially unresectable HCC patients who attain favorable responses to conversion therapy, providing high-level evidence for clinical decision-making.

Вмешательства

• Другое Surgical Resection
  Patients in the Surgical Resection (SR) cohort should undergo curative resection within 1-2 weeks after the index date. Perioperative medication management shall be conducted in accordance with the participating center's standards, and unified pathological assessments shall be performed for pathological complete response (pCR), major pathological response (MPR), and surgical margin status. Adjuvant therapy shall be initiated 4-8 weeks postoperatively, using the same preoperative PD-1/PD-L1 inhib
• Другое Maintenance Therapy Group
  Patients in the Maintenance Therapy (MT) cohort shall continue treatment with PD-1/PD-L1 inhibitor ± tyrosine kinase inhibitor (TKI) starting from the index date, until the occurrence of radiological progression, death, or fulfillment of the drug discontinuation criteria. \[The index date is defined as the first date on which the Multidisciplinary Team (MDT) simultaneously confirms that "complete response (CR)/partial response (PR) has been achieved and surgical resection is feasible," and it s

Первичные конечные точки

• Time to Treatment Failure (TTF) per RECIST v1.1 [Срок оценки: From date of enrollment until treatment failure, assessed up to 36 months]

Вторичные конечные точки (5)

• Time to Treatment Failure (TTF) per mRECIST [Срок оценки: From date of enrollment until treatment failure, assessed up to 36 months]
• Overall Survival (OS) [Срок оценки: From date of enrollment until death, assessed up to 36 months]
• 12-month Overall Survival (OS) Rate [Срок оценки: At 12 months post-enrollment]
• Pattern of Recurrence or Progression [Срок оценки: From date of enrollment until first recurrence/progression, assessed up to 36 months]
• Incidence of Adverse Events (AEs) [Срок оценки: From date of enrollment through 90 days after the last dose of study treatment or surgery]

Критерии участия

Критерии включения

• Aged 18-80 years.
• Diagnosed with locally advanced, metastatic, and/or initially unresectable hepatocellular carcinoma (uHCC) via histology/cytology or clinical criteria (AASLD standards for cirrhotic patients; histopathological confirmation required for non-cirrhotic patients).
• Previously judged unresectable or inappropriate for resection by MDT during initial diagnosis or disease course, with at least one evaluable lesion per RECIST v1.1.
• Completed conversion therapy \[systemic therapy (PD-1/PD-L1 ± TKI) ± local therapy (TACE/HAIC/radiation/ablation, etc.)\], achieved CR or PR (primarily assessed by mRECIST, with concurrent RECIST v1.1 documentation), and confirmed via re-evaluation with the same imaging modality ≥4 weeks later.
• Meets necessary conditions for resection: Child-Pugh Class A liver function, ICG R15 <30%, and future liver remnant (FLR) accounting for ≥40% of standard liver volume (SLV) in patients with chronic liver disease, hepatic parenchymal injury, or cirrhosis, or ≥30% in patients without liver fibrosis or cirrhosis.
• For patients with previous portal vein/hepatic vein/inferior vena cava tumor thrombus (without atrial tumor thrombus), enrollment is permitted only if the thrombus has significantly regressed after conversion therapy, MDT confirms feasibility of R0 resection, and risks are acceptable.
• ECOG performance status 0-1.
• Adequate organ and bone marrow function, as evidenced by: hemoglobin ≥90g/L; absolute neutrophil count ≥1.5×10⁹/L; platelets ≥60×10⁹/L; total bilirubin ≤1.5×upper limit of normal (ULN); AST, ALT, and ALP ≤2.5×ULN; serum creatinine ≤1.5×ULN or estimated creatinine clearance ≥50ml/min (Cockcroft-Gault formula); urine protein <(++) or 24-hour urine protein <1.0g.
• Normal coagulation function without active bleeding: INR ≤1.5×ULN; APTT ≤1.5×ULN.
• For patients with active hepatitis B virus (HBV) infection: those already receiving anti-HBV therapy (per local standard treatment) must agree to continue during the study; those not receiving anti-HBV therapy must initiate treatment (per local standard treatment) during screening and agree to continue throughout the study.
• For patients with HCV infection: excluded if HCV RNA is detectable.
• No pregnancy or pregnancy plans: fertile females must have a negative urine/serum pregnancy test within 7 days before first dosing and agree to use effective contraception during the study and for 120 days after last dosing; non-sterilized males must agree to use effective contraception during the study and for 120 days after last dosing.

Критерии исключения

• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma-HCC.
• Extrahepatic metastasis confirmed by chest, abdominal, and pelvic CT and/or MRI.
• Inability to achieve R0 resection.
• Previous liver transplantation or on the liver transplantation waiting list.
• Decompensated cirrhosis (persistent or refractory ascites, hepatic encephalopathy, progressive jaundice, etc.); Child-Pugh Class B with score ≥8 or Class C; ALBI Grade 3.
• Significant and uncontrollable portal hypertension (e.g., markedly elevated HVPG with recurrent variceal bleeding, refractory ascites).
• Active gastrointestinal bleeding within the past 4 weeks or uncorrectable coagulation disorders.
• Active infection/sepsis or unresolved Grade ≥2 immune-related adverse events (irAEs).
• Severe cardiopulmonary/renal insufficiency (e.g., NYHA Class III-IV, recent myocardial infarction/stroke, dialysis dependency).
• Pregnancy or lactation.
• Other active malignant tumors within the past 5 years (exceptions for low-risk tumors such as basal cell carcinoma of the skin or carcinoma in situ of the cervix).
• Inability to undergo standardized imaging assessments (multiphase contrast-enhanced CT/MRI) or poor compliance.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07410715 · 2025-2584

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗