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

Sun Yat-sen University

Status and phase: Enrolling; Phase 2

Conditions: Hepatoblastoma

Treatments: Drug: Very low-risk group; Drug: Low-risk group; Drug: Intermediate-risk group; Drug: High-risk group; Other: 5hmc dynamic monitoring

Study type: Interventional

Funder types: Other

Identifiers

NCT07300449

SCCG-HB

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: Under 18 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 4 patient groups

Arm 1: Very low-risk group

Experimental group

Description:

The study used CHIC staging to stage hepatoblastoma

Treatment:

Other: 5hmc dynamic monitoring

Drug: Very low-risk group

Arm 2: low risk group

Experimental group

Description:

Patients received 2 to 4 courses of DDP monotherapy followed by elective surgery, then 2 additional courses of DDP monotherapy postoperatively, totaling 4 to 6 treatment cycles.

Treatment:

Other: 5hmc dynamic monitoring

Drug: Low-risk group

Arm 3：intermediate risk group

Experimental group

Description:

Treatment protocol randomization: Group A received SIOPEL-3 HR chemotherapy for 2-4 cycles followed by elective surgery, with continued chemotherapy for 6 additional cycles postoperatively. The patients in group B were given C5VD chemotherapy for 2-4 courses and then underwent elective operation.

Treatment:

Other: 5hmc dynamic monitoring

Drug: Intermediate-risk group

Arm 4： High risk group

Experimental group

Description:

Surgical resection after 3-5 courses of C-CD+ICE+solanifin chemotherapy

Treatment:

Other: 5hmc dynamic monitoring

Drug: High-risk group