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HepatoblastomaPhase 3NCT04478292

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

A Phase 3 study testing Sodium Thiosulfate Injection, Primary surgery resection and mono CDDP-Group A2 in people with Hepatoblastoma, run by Shanghai Children's Medical Center at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages Up to 18 years
Conditions the study is for
Hepatoblastoma
What is being tested?
Sodium Thiosulfate Injection, Primary surgery resection and mono CDDP-Group A2
Could I receive a placebo?
No, everyone receives an active treatment
How many people
330 participants
Where
1 siteChina
Study dates
1 Mar 2021to 30 Sep 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Performance Level Patients must have a performance status corresponding to ECOG scores 0, 1, or 2. Use Karnofsky for patients >16 years of age and Lansky for patients ≤16 years of age.
  • Diagnosis Patients must be newly diagnosed with histologically-proven primary pediatric HB
  • Emergent Treatment for HB In emergency situation when a patient meets all other eligibility criteria and has had baseline required observations, but is too ill to undergo a biopsy safely, the patient may be enrolled without a biopsy.
  • Prior Therapy Patients may have had surgical resection of the hepatic malignancy prior to enrollment. All other anti-cancer therapy for the current liver lesion is prohibited.
  • Organ Function Requirements
  • Adequate renal function defined as:
Show all 11Show fewer
  • Creatinine clearance or radioisotope Glomerular Filtration Rate (GFR) ≥ 70 mL/min/1.73 m2
  • 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.
  • 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)

Who cannot join

  • Prior chemotherapy or tumor directed therapy expect for surgical resection of the hepatic malignancy (i.e. radiation therapy, biologic agents, local therapy (embolization, radiofrequency ablation, and laser)). Therefore, patients with a pre-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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Haishan Ruan, MS contact

+8618801902467

ruanhaishan@scmc.com.cn

Yujia Tang, MD contact

+8618516342079

tangyuejia@scmc.com.cn

China1 site, 1 recruiting

  • Shanghai Children's Medical Center

    Shanghai, Shanghai Municipality, 200127

    Hongxiang Gao, M.D., +8615216606578, gaohongxiang@scmc.com.cn

    YiJin Gao, Ph.D.

    Recruiting

Other trials in China

About this study

Official title: A Phase 3 Multi-institutional Study for Treatment of Children With Newly Diagnosed Hepatoblastoma Using a Modified PHITT Strategy Incorporating a Randomized Assessment of Sodium Thiosulfate as Otoprotection for Children With Localized Disease, and Response Adapted Therapy for Patients With Metastatic Disease

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

Read the detailed 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.
Conditions
Hepatoblastoma
Being tested
Sodium Thiosulfate Injection, Primary surgery resection, mono CDDP-Group A2, Cisplatin, 5-Fluorouracil, Vincristine, Doxorubicin-Group C, Biopsy
Keywords
hepatoblastoma, sodium thiosulfate, auditory protection
Medical subject headings
Hepatoblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sodium Thiosulfate InjectionDrug

    Also called STS

    Weight ≥ 10 kg: 20 g/m2/dose STS or Weight 5-10 kg: 15 g/m2/dose STS or Weight < 5 kg: 10 g/m2/dose STS will be administered by IV over 2 hours beginning 6 hours after the completion of each cisplatin infusion.

  • Primary surgery resectionProcedure or surgery

    Resection of the primary tumor up-front

  • mono CDDP-Group A2Drug

    Cisplatin 100 mg/m2/dose Day 1 . All non-WDF patients (A2) will receive 2 cycles of mono cisplatin (100 mg/m2/dose) chemotherapy. Each cycle lasts 3 weeks (21 days).

  • Cisplatin, 5-Fluorouracil, Vincristine, Doxorubicin-Group CDrug

    Also called C5VD Group C

    All the patients in Group C (2 arms) will receive 6 cycles chemotherapy in total. Cisplatin 100 mg/m2/dose Day 1; 5-Fluorouracil 600 mg/m2/dose Day 1; Vincristine 1.5 mg/m2/dose Day 1,8 and 15; Doxorubicin 30 mg/m2/dose Day 1 and 2; (Dexrazoxane : 300 mg/m2/dose Day 1 and 2, where is available)

  • BiopsyProcedure or surgery

    Tumors are deemed unresectable at diagnosis.

  • Resection or transplantProcedure or surgery

    Ideal timing to resect of the primary tumors or transplant if if excellent response achieved at 1st or 2nd evaluation timepoint. But surgery timing is not mandated. Irrespective of the timing of surgery, patients should complete all planned protocol cycles of chemotherapy (including post transplantation). If surgical resection of the primary tumor is delayed until the end of therapy, no further post-operative chemotherapy should be given.

  • Resection of pulmonary nodulesProcedure or surgery

    Resection of pulmonary nodules should be considered in Group D2, patients at any cycle if continuing to respond to consolidation therapy.

  • mono CDDP- Group BDrug

    Cisplatin 80 mg/m2/dose Day 1. All patients in Group B (2 arms) will receive 6 cycles of mono cisplatin chemotherapy. Each cycle lasts 2 weeks (14 days).

  • Block 1 to 3 (Cisplatin, Doxorubicin) Group DDrug

    Block 1 and 2: Cisplatin 70 mg/m2/dose Day1, 8 and 15; Doxorubicin 30 mg/m2/dose, Day 8 and 9; (Dexrazoxane: 300 mg/m2/dose Day 1 and 2, where is available); Block 3: Cisplatin 70 mg/m2/dose Day1and 8; Doxorubicin 30 mg/m2/dose Day 8 and 9; (Dexrazoxane BSA ≥ 0.6 m2/dose: 300 mg/m2/dose Day 8 and 9, where is available) All patients in Group D will receive 3 blocks in induction, followed by consolidation therapy. Block 1 and 2 last 28 days. Block 3 is 21 cycles.

  • Consolidation (Carboplatin, Doxorubicin) -Group D1Drug

    Also called Group D1 CD

    Following Block 1-3 of induction therapy, Group D1 patients will receive 3 cycles of Carboplatin + Doxorubicin consolidation therapy. Each cycle lasts 3 weeks (21 days). Carboplatin 500 mg/m2/dose Day 1; Doxorubicin 20 mg/m2/dose Day 1 and 2; (Dexrazoxane: 200 mg/m2/dose Day 1 and 2, where is available).

  • Consolidation (Carboplatin +Doxorubicin/Vincristine + Irinotecan)-Group D2Drug

    Also called Group D2 CD/VI

    Following Block 1-3 of induction therapy, patients in Group D2, will receive 6 cycles of consolidation chemotherapy with Carboplatin + Doxorubicin in Cycles 1, 3, and 5 alternating with Vincristine + irinotecan in Cycles 2, 4, and 6. One cycle of therapy lasts 3 weeks (21 days). Cycle 1, 3 and 5: Carboplatin 500 mg/m2/dose Day 1; Doxorubicin 20 mg/m2/dose Day 1 and 2; (Dexrazoxane: 200 mg/m2/dose Day 1 and 2, where is available).

    Cycle 2, 4 and 6: Vincristine 1.5 mg/m2/dose, Day 1 and 8; Irinotecan 50 mg/m2/dose, Day 1 to 5;

Study groups in NCT04478292
Study groupRoleWhat they receive
Group AExperimental* Group A1： tumor is completely resected at diagnosis and receives no adjuvant chemotherapy（well differentiated fetal [WDF] histology HB) ； * Group A2：tumor is completely resected followed by 2 cycles of standard dose cisplatin monotherapy （non-well differentiated fetal histology HB)
Receives: Procedure: Primary surgery resection; Drug: mono CDDP-Group A2
Group BExperimental* Patients will be randomized to one of 2 arms: Arm CDDP or Arm CDDP plus STS. In each arm, patients will be stratified by resectablity after completion of 2 cycles of protocol therapy (6 cycles of standard dose cisplatin monotherapy with or without STS). All the patients in 2 arms will receive 6 cycles chemotherapy in total. * Resection of the primary tumor will be performed after completing the 2nd cycle of chemotherapy. * Those patients whose tumors after 2 cycles do not meet criteria for definitive surgical, 2nd resectablity evaluation will be scheduled after 4 cycles of chemotherapy.
Receives: Drug: Sodium Thiosulfate Injection; Procedure: Biopsy; Procedure: Resection or transplant; Drug: mono CDDP- Group B
Group CExperimental* Patients in Group C will have locally advanced tumors including PRETEXT I-III tumors with a positive VPEFR annotation factor and all PRETEXT IV tumors. * Patients will be randomized to one of 2 arms: Arm C5VD or Arm C5VD plus STS. In each arm, patients will be stratified by resectablity after completion of 2 cycles of protocol therapy. All the patients in 2 arms will receive 6 cycles chemotherapy in total. * Resection of the primary tumor will be performed after completing the 2nd cycle of chemotherapy. * Those patients whose tumors after 2 cycles do not meet criteria for definitive surgical, 2nd resectablity evaluation will be scheduled after 4 cycles of chemotherapy.
Receives: Drug: Sodium Thiosulfate Injection; Drug: Cisplatin, 5-Fluorouracil, Vincristine, Doxorubicin-Group C; Procedure: Biopsy; Procedure: Resection or transplant
Group DExperimental* These patients have metastatic disease, suspected HB patients ≥ 8 years of age, or have an AFP ≤ 100 at diagnosis. * Patients will receive initial chemotherapy according to the cisplatin-intensive SIOPEL-4 induction regimen. Resection (including transplant) of the primary tumor should be completed after induction Block 3, but primary tumor resection can be planned any time after completing induction therapy. * Following 3 blocks of induction chemotherapy, patients will be stratified into 2 risk groups: Group D1 includes patients who either have a chemotherapy-induced lung CR or are rendered a lung CR by surgical metastasectomy. These patients will have chemotherapy consolidation with carboplatin/doxorubicin. In Group D2, patients will have not yet achieved a lung CR at the end of induction Block 3. These patients will get intensified consolidation therapy of carboplatin/doxorubicin with vincristine/irinotecan. * Resection of pulmonary nodules should be considered in Group D2.
Receives: Procedure: Biopsy; Procedure: Resection or transplant; Procedure: Resection of pulmonary nodules; Drug: Block 1 to 3 (Cisplatin, Doxorubicin) Group D; Drug: Consolidation (Carboplatin, Doxorubicin) -Group D1; Drug: Consolidation (Carboplatin +Doxorubicin/Vincristine + Irinotecan)-Group D2

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Audiogram

    The grade (from 0 to 4, higher scores mean a worse outcome) of audiograms evaluated by Boston Grading Scale for Ototoxicity.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).

    Measured: From diagnosis through study completion, an average of 1 year

  2. 3 -year Event-free survival (EFS)

    Calculated from the time of randomisation to the first of the following events: progression, relapse, secondary malignancy or death.

    Measured: UP to 3years

Secondary outcomes (2)

  1. Treatment-related adverse events

    Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0

    Measured: UP to 3years

  2. Response to chemotherapy

    Complete response (CR):

    no evidence of disease and normal serum AFP value (for age).

    Partial response (PR):

    any tumour volume shrinkage associated with a decreasing serum AFP value, > 1 log below the original measurement.

    Stable disease (SD):

    no tumour volume change and no change, or < 1 log fall of the serum AFP concentration.

    Progressive disease (PD):

    unequivocal increase in 1 or more dimensions and/or any unequivocal increase of the serum AFP concentration (three successive 1-2 weekly determinations) even without clinical (physical and/or radiological) evidence of tumour re-growth.

    Measured: UP to 3years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jul 2020
  2. Study start1 Mar 2021
  3. Primary completion31 Mar 2027 (estimated)
  4. Study completion30 Sep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
330 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04478292
Sponsor's protocol ID
NCMC-SH-HEP-2020
Status last verified
Apr 2026
First submitted
8 Jun 2020
Last updated
4 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Study protocol, SAP and ICF were shared before study initiation. Patient data and the information about the process of the study will be shared within the 3 participants annually after enrollment patients.

Publications

  • Brock PR, Maibach R, Childs M, Rajput K, Roebuck D, Sullivan MJ, Laithier V, Ronghe M, Dall'Igna P, Hiyama E, Brichard B, Skeen J, Mateos ME, Capra M, Rangaswami AA, Ansari M, Rechnitzer C, Veal GJ, Covezzoli A, Brugieres L, Perilongo G, Czauderna P, Morland B, Neuwelt EA. Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss. N Engl J Med. 2018 Jun 21;378(25):2376-2385. doi: 10.1056/NEJMoa1801109.

    PubMed 29924955

  • Freyer DR, Chen L, Krailo MD, Knight K, Villaluna D, Bliss B, Pollock BH, Ramdas J, Lange B, Van Hoff D, VanSoelen ML, Wiernikowski J, Neuwelt EA, Sung L. Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer (ACCL0431): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2017 Jan;18(1):63-74. doi: 10.1016/S1470-2045(16)30625-8. Epub 2016 Dec 1.

    PubMed 27914822

  • Freyer DR, Brock P, Knight K, Reaman G, Cabral S, Robinson PD, Sung L. Interventions for cisplatin-induced hearing loss in children and adolescents with cancer. Lancet Child Adolesc Health. 2019 Aug;3(8):578-584. doi: 10.1016/S2352-4642(19)30115-4. Epub 2019 May 31.

    PubMed 31160205

  • Meyers RL, Maibach R, Hiyama E, Haberle B, Krailo M, Rangaswami A, Aronson DC, Malogolowkin MH, Perilongo G, von Schweinitz D, Ansari M, Lopez-Terrada D, Tanaka Y, Alaggio R, Leuschner I, Hishiki T, Schmid I, Watanabe K, Yoshimura K, Feng Y, Rinaldi E, Saraceno D, Derosa M, Czauderna P. Risk-stratified staging in paediatric hepatoblastoma: a unified analysis from the Children's Hepatic tumors International Collaboration. Lancet Oncol. 2017 Jan;18(1):122-131. doi: 10.1016/S1470-2045(16)30598-8. Epub 2016 Nov 22.

    PubMed 27884679

  • Brock PR, Knight KR, Freyer DR, Campbell KC, Steyger PS, Blakley BW, Rassekh SR, Chang KW, Fligor BJ, Rajput K, Sullivan M, Neuwelt EA. Platinum-induced ototoxicity in children: a consensus review on mechanisms, predisposition, and protection, including a new International Society of Pediatric Oncology Boston ototoxicity scale. J Clin Oncol. 2012 Jul 1;30(19):2408-17. doi: 10.1200/JCO.2011.39.1110. Epub 2012 Apr 30.

    PubMed 22547603

  • Zsiros J, Brugieres L, Brock P, Roebuck D, Maibach R, Zimmermann A, Childs M, Pariente D, Laithier V, Otte JB, Branchereau S, Aronson D, Rangaswami A, Ronghe M, Casanova M, Sullivan M, Morland B, Czauderna P, Perilongo G; International Childhood Liver Tumours Strategy Group (SIOPEL). Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): a prospective, single-arm, feasibility study. Lancet Oncol. 2013 Aug;14(9):834-42. doi: 10.1016/S1470-2045(13)70272-9. Epub 2013 Jul 4.

    PubMed 23831416

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sodium Thiosulfate Injection, Primary surgery resection and mono CDDP-Group A2 in people with Hepatoblastoma, run by Shanghai Children's Medical Center at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 4 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Haishan Ruan, MS (+8618801902467, ruanhaishan@scmc.com.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Audiogram (time frame: From diagnosis through study completion, an average of 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04478292, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2026.

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