A Prospective Multicenter Clinical Study of SCCG Protocol and ctDNA 5hmc in Predicting the Chemotherapy Sensitivity and Monitoring the Recurrence and Metastasis of Hepatoblastoma in Children and Adolescents

Official title

A Prospective Multicenter Clinical Study of the South China Collaborative Group Protocol for the Treatment of Hepatoblastoma in Children and Adolescents

Overview

Hepatoblastoma is the most common malignant liver tumor in infants and preschool children, comprising 65% of pediatric liver malignancies in those under 15, with its incidence on the rise in recent years \[1\]. Standard therapy combines surgical resection and chemotherapy: early-stage patients boast a survival rate over 90%, yet high-risk cases only reach around 40%, highlighting unmet treatment needs. Notably, there is no universal definition for high-risk hepatoblastoma. The U.S. COG (AHEP0731) categorizes it as stage 4 disease, AFP \<100ng/ml at diagnosis (any stage), or small cell undifferentiated histology; conversely, SIOP includes factors like major vascular invasion (inferior vena cava/portal vein), intra-abdominal extrahepatic spread, distant metastasis, AFP \<100ng/ml, or tumor rupture, regardless of PRETEXT stage. To improve outcomes, international teams have tested intensified chemotherapy: Europe's SIOPEL reported that escalated cisplatin-doxorubicin regimens lifted high-risk patients' 3-year overall survival to over 80% \[2\], though with heightened toxicity. Similarly, Germany's IPA (ifosfamide-cisplatin-doxorubicin) and Japan's ITEC (ifosfamide-doxorubicin-carboplatin-VP-16) regimens delivered significant survival benefits but also amplified side effects \[3,4\]. Against this backdrop, the Guangdong Anti-Cancer Association's Pediatric Oncology Committee, led by Sun Yat-sen University Cancer Center and involving 15 hospitals, is launching a multicenter prospective trial to identify optimal chemotherapy regimens for Chinese hepatoblastoma children. Parallelly, liquid biopsy has become an oncology research priority, offering four core advantages over tissue biopsy: non-invasiveness (peripheral blood sampling avoids tumor seeding), real-time genetic/progression monitoring (eliminating repeated invasive procedures), comprehensive molecular profiling (overcoming intratumoral heterogeneity), and high accuracy (capturing primary tumor-derived data). Given hepatoblastoma's propensity for early distant metastasis and 30-40% advanced-stage survival (with limited late-stage chemo efficacy), the Nano-5hmC-Seal cfDNA epigenetic profiling method holds promise as a novel biomarker for early diagnosis, treatment prediction, recurrence monitoring, and prognosis assessment in this disease.

Detailed description

Sun Yat-sen University Cancer Center, the Guangdong Anti-Cancer Association's Pediatric Oncology Committee (15 participating hospitals) is launching a multicenter prospective trial to optimize chemotherapy for Chinese patients.

Liquid biopsy, with advantages of non-invasiveness, real-time monitoring, comprehensive profiling, and high accuracy, is an oncology priority. Given hepatoblastoma's early metastasis and poor advanced-stage outcomes (30-40% survival), Nano-5hmC-Seal cfDNA epigenetic profiling is a promising biomarker for diagnosis, treatment prediction, recurrence monitoring, and prognosis.

Interventions

• Drug Very low-risk group
  Very low-risk group: No chemotherapy after pure fetal type surgery, followed up and observed. Chemotherapy with other types of single-agent DDP regimens for 4 courses.
• Drug Low-risk group
  Low-risk group: 2 to 4 courses of DDP monotherapy chemotherapy, elective surgery, 2 courses of DDP monotherapy chemotherapy after surgery, totaling 4 to 6 courses.
• Drug Intermediate-risk group
  Intermediate risk group: randomized treatment: group A SIOPEL - 3 HR solutions can be 2 \~ 4 course of chemotherapy, continue to A total of 6 course of chemotherapy after surgery. Group B C5VD solution after 2 \~ 4 course of chemotherapy, elective surgical procedures continue to a total of 6 course of chemotherapy after surgery.
• Drug High-risk group
  High-risk group：Chemotherapy with the C-CD+ICE+ sorafenib regimen for 3 to 5 courses was followed by elective surgery, with a total of 6 to 7 courses
• Other 5hmc dynamic monitoring
  Peripheral blood was regularly drawn from patients in the very low-risk group, low-risk group, intermediate-risk group and high-risk group for 5hmc dynamic monitoring to evaluate its value in clinical efficacy and recurrence detection

Primary outcome measures

• PFS [Time frame: PFS is defined as the time interval from the start of treatment until the occurrence of disease progression or death of the patient from any cause, whichever happens first (up to 24 months）.]

Secondary outcome measures (2)

• OS [Time frame: The assessment of OS will be carried out over an estimated period of up to 24 months.]
• Consistency [Time frame: The assessment will be carried out over an estimated period of up to 24 months.]

Eligibility criteria

Inclusion criteria

• Patients with primary hepatoblastoma confirmed by pathology.

• The age of the subjects was less than 18 years old. ③ Obtain the informed consent from the guardians and sign the informed consent form

Exclusion criteria

• Recurrent hepatoblastoma or other malignant tumor.

• Age> 18 years old. ③ Patients with other tumors and received chemotherapy and abdominal radiotherapy.

• Heart, brain and kidney failure patients.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• Sun Yat-sen University Cancer Center — Guangzhou
• Sun Yat-sen University Cancer Center — Guangzhou

Identifiers

NCT: NCT07300449 · SCCG-HB

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗