JPLT4:PHITT

JRCT ID: jRCTs061180004

Registered date:31/10/2018

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: hepatoblastoma, hepatocellular carcinoma
• Date of first enrollment: 13/11/2018
• Target sample size: 263
• Countries of recruitment: East Asia(Taiwan, Hong Kong, Singapore and other),Japan
• Study type: Interventional

Intervention(s)

Group A - Very Low Risk HB Patients: The patients will have a primary resection of their tumor. Following surgical resection, patients with Well Differentiated Fetal(WDF) histology must receive no adjuvant chemotherapy. All non-WDF patients will receive 2 cycles at 21 day intervals of cisplatin (100mg/m2) chemotherapy (CDDP-M).
Group B - Low Risk HB Patients: The patients will have a tumors deemed unresectable at diagnosis but no other adverse features. Patients resected after 2 cycles at 14 day intervals of chemotherapy (cisplatin 80mg/m2) will be eligible for a randomization comparing 2 vs. 4 cycles of post-operative chemotherapy.
Group C - Intermediate Risk HB Patients:Patients will have locally advanced tumors including PRETEXT I-III tumors with a positive annotation factor and all PRETEXT IV tumors. Patients will be randomized to one of 2 chemotherapy arms:C5VD(Cisplatin 100mg/m2, 5-FU 600mg/m2, Doxorubicin 30mg/m2 x2, Vincristine 1.5mg/m2 x3) at 21 day intervals or higher dose CDDP-M(Cisplatin 100mg/m2) at 14 day intervals. The resection of the primary tumor can be considered at ANY point during therapy, but should occur at least prior to the last 2 cycles of chemotherapy when possible.
Group D - High Risk HB Patients: The patients will have pulmonary metastatic disease. Patients will receive initial chemotherapy according to the cisplatin-intensive SIOPEL-4 regimen. Following 3 blocks of chemotherapy patients will be stratified into 2 risk groups. In Group D1, the patients who will either have had a chemotherapy-induced lung CR, or will be rendered a lung CR by surgical metastectomy (recommended before resection of the primary tumor) will have chemotherapy consolidation with carboplatin/doxorubicin. Patients who have not achieved a lung CR (either with chemotherapy and/or surgery) at the end of block A3 will be randomized to intensified 6 courses at 21 day intervals of consolidation therapy of carboplatin (500mg/m2)/doxorubicin (20mg/m2 X2) with either carboplatin (400mg/m2 X2)/ etoposide (200mg/m2 X2) (Group D2) or vincristine (1.5mg/m2 at 1 and 8 days & irinotecan 50mg/m2 at 1-5 days) (Group D3).
Group E - Resected hepatocellular carcinoma (HCC) Patients: In the Patients who have an underlying predisposition to HCC through genetic, viral or metabolic conditions (Group E1), the recommendation is for these patients to receive no adjuvant chemotherapy. : Patients (Group E2) with de novo HCC will receive 4 cycles of PLADO chemotherapy(cisplatin(80mg/m2) / doxorubicin (30mg/m2 x2).
Group F - Unresected/metastatic HCC Patients: Patients will be randomized to preoperative chemotherapy consisting of either 3 courses of every 21 days with PLADO + sorafenib (150mg/m2 twice daily orally at 3-21 days) or 4 courses of every 14 days with either regimens of PLADO + sorafenib (150mg/m2 twice daily orally at 3-14 days) /GEMOX(gemcitabin 1000mg/m2 and oxaliplati 100mg/m2) +sorafenib(150mg/m2 twice daily orally at 2-14 days).

Outcome(s)

Primary Outcome

1)To evaluate if the treatment of Low Risk hepatoblastoma (HB) can be reduced (Group B1)
2)To compare different treatment regimens for Intermediate risk HB (Group C)
3)To compare different post induction treatment regimens for High Risk HB (Group D2)
4)To determine if the outcome is improved when GEMOX is added to PLADO in the treatment of unresected hepatocellular carcinoma HCC (Group F)
5)To collect samples for biological and toxicity studies. (All groups)

Secondary Outcome

1)To report outcome (including event-free survival (EFS), failure-free survival (FFS), overall survival (OS), toxicity and surgical outcome) in all patient groups.
2)To validate a new global risk stratification, defined by Children's Hepatic Tumours International Collaboration (CHIC)
3)To evaluate clinically relevant factors, including the following:
- Provide a comprehensive and highly-validated panel of diagnostic and prognostic biomarkers
- Determine if paediatric HCC is a biologically different entity to adult HCC
- Develop genomic and/or biomarker analysis to predict children who may have an increased risk of developing toxicity with chemotherapy.
4)To establish a collection of clinically and pathologically-annotated biological samples.
5)Evaluate a surgical planning tool for an impact on decision making processes in POST-TEXT III and IV HB

Key inclusion & exclusion criteria

• Age minimum: >=
• Age maximum: <= 30age old
• Gender: Both

Include criteria

1)Clinical diagnosis of hepatoblstoma (HB) and histologically defined diagnosis of HB or hepatocellular carcinoma (HCC).*
2)Age <=30 years
3)Written informed consent for trial entry

Exclude criteria

1)Any previous chemotherapy or currently receiving anti-cancer agents
2)Recurrent disease
3)Previously received a solid organ transplant; other than orthotopic liver transplantation (OLT).
4)Uncontrolled infection
5)Unable to follow or comply with the protocol for any reason
6)Second malignancy
7)Pregnant or breastfeeding women

Related Information

• Primary Sponsor: Hiyama Eiso