A Multi-institutional Study for Treatment of Children With Newly Diagnosed Hepatoblastoma Using a Modified PHITT Strategy

Last updated: May 14, 2025
Sponsor: Shanghai Children's Medical Center
Overall Status: Active - Recruiting

Phase

3

Condition

Hepatoblastoma

Treatment

Consolidation (Carboplatin +Doxorubicin/Vincristine + Irinotecan)-Group D2

Sodium Thiosulfate Injection

Biopsy

Clinical Study ID

NCT04478292
NCMC-SH-HEP-2020
  • Ages < 18
  • All Genders

Study Summary

A Phase 3 multi-institutional study for treatment of children with newly diagnosed hepatoblastoma using a modified Paediatric Hepatic International Tumour Trial (PHITT) strategy incorporating a randomized assessment of sodium thiosulfate as auditory protection for children with localized disease, and response adapted therapy for patients with metastatic disease

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Performance Level Patients must have a performance status corresponding to ECOGscores 0, 1, or 2. Use Karnofsky for patients >16 years of age and Lansky forpatients ≤16 years of age.

  • Diagnosis Patients must be newly diagnosed with histologically-proven primarypediatric HB

  • Emergent Treatment for HB In emergency situation when a patient meets all othereligibility criteria and has had baseline required observations, but is too ill toundergo a biopsy safely, the patient may be enrolled without a biopsy.

  • Prior Therapy Patients may have had surgical resection of the hepatic malignancyprior to enrollment. All other anti-cancer therapy for the current liver lesion isprohibited.

  • Organ Function Requirements

I) Adequate renal function defined as:

Creatinine clearance or radioisotope Glomerular Filtration Rate (GFR) ≥ 70 mL/min/1.73 m2

II) Adequate liver function defined as:

Total bilirubin ≤ 5 x upper limit of normal (ULN) for age, and Aspartate aminotransferase (AST) or Alanine transaminase (ALT) < 10 x upper limit of normal (ULN) for age.

III) Adequate pulmonary function defined as:

Normal pulmonary function tests (including DLCO) if there is clinical indication for determination (e.g. dyspnea at rest, known requirement for supplemental oxygen)

Exclusion

Exclusion Criteria:

  • Prior chemotherapy or tumor directed therapy expect for surgical resection of thehepatic malignancy (i.e. radiation therapy, biologic agents, local therapy (embolization, radiofrequency ablation, and laser)). Therefore, patients with apre-disposition syndrome who have a prior malignancy are not eligible.

  • Patients who are currently receiving another investigational drug.

  • Patients who are currently receiving other anticancer agents.

  • Patients with uncontrolled infection.

  • Patients who previously received a solid organ transplant.

Study Design

Total Participants: 330
Treatment Group(s): 11
Primary Treatment: Consolidation (Carboplatin +Doxorubicin/Vincristine + Irinotecan)-Group D2
Phase: 3
Study Start date:
March 01, 2021
Estimated Completion Date:
September 30, 2027

Study Description

Primary aims:

  1. Localized Disease: Groups B and C: To evaluate and validate the efficacy of sodium thiosulfate (STS) to reduce the hearing impairment caused by a cisplatin monotherapy in non-metastatic patients without adverse features (localized PRETEXT I-III tumors without positive VPEFR annotation factors) (Group B - treated with cisplatin mono-therapy) or with adverse features (localized PRETEXT I-III tumors with positive VPEFR annotation factors) (Group C - treated with regimen C5VD)

  2. Metastatic Disease: Group D: To determine the 3-year Event-free survival (EFS) in patients with metastatic disease treated with International Society of Paediatric Oncology (SIOPEL 4) induction therapy followed by response adapted consolidation therapy.

  3. To determine the 3-year EFS in patients with HB whose tumor is completely resected at diagnosis (Group A) and either receive no adjuvant chemotherapy (Group A1, completely resected well differentiated fetal (WDF) histology HB) or 2 cycles of standard dose cisplatin monotherapy (Group A2, completely resected non-well differentiated fetal histology HB)

Secondary aims:

  1. To determine any impact of STS on chemotherapy response and survival in children with localized hepatoblastoma

  2. To assess the feasibility of complete resection after 2 cycles of interval compressed lower dose cisplatin monotherapy (80 mg/m2/cycle) in non-metastatic patients and without adverse features

  3. To assess the feasibility of complete resection after 2 cycles of C5VD in non-metastatic patients with adverse features.5. To determine the adherence to PRETEXT and Post-treatment extent of disease (POSTTEXT) based surgical guidelines

  4. To determine the prognostic relevance in HB of a "small cell undifferentiated", tumor component, percentage of tumor necrosis in post chemotherapy specimens, and the relevance of a positive microscopic margin in resected HB specimens.

  5. To determine the concordance between institutional, regional expert panel (prospective) and international expert panel (retrospective) review assessment of PRETEXT and POSTTEXT stage, and correlate with outcome variables.

  6. To prospectively collect patient HB tumor, peripheral blood and urine specimens, for translational biology studies.

Connect with a study center

  • Shanghai Children's Medical Center

    Shanghai, Shanghai 200127
    China

    Active - Recruiting

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