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

ConditionHepatoblastoma
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
AgeUp to 18
SponsorShanghai Children's Medical Center

About this trial

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

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Sodium Thiosulfate Injection

    Drug

    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 resection

    Procedure/Surgery

    Resection of the primary tumor up-front

  • mono CDDP-Group A2

    Drug

    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 C

    Drug

    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)

  • Biopsy

    Procedure/Surgery

    Tumors are deemed unresectable at diagnosis.

  • Resection or transplant

    Procedure/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 nodules

    Procedure/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 B

    Drug

    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 D

    Drug

    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 D1

    Drug

    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 D2

    Drug

    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;

Treatment groups

330 Participants
are divided into 4 treatment groups
Group A: Group AExperimental treatment 2 interventions
Group B: Group BExperimental treatment 4 interventions
Group C: Group CExperimental treatment 4 interventions
Group D: Group DExperimental treatment 6 interventions

Trial outcomes

Primary outcomes

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).

Time frame
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.

Time frame
UP to 3years

Secondary outcomes

1

Treatment-related adverse events

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

Time frame
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.

Time frame
UP to 3years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Shanghai Children's Medical Center

Lead sponsor

Shanghai Children's Hospital

Collaborator

Source ClinicalTrials.gov
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