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

Sponsor
Shanghai Children's Medical Center
Study ID
NCT04478292
Phase
PHASE3
Status
Recruiting
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Conditions

  • Hepatoblastoma

Eligibility Criteria

Sex
ALL
Age
N/A - 18 Years
Healthy Volunteers
Not accepted

Interventions

  • 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
    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
    Tumors are deemed unresectable at diagnosis.
  • Resection or transplant — PROCEDURE
    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
    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;

Study Details

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

Key Dates

Start date
Mar 1, 2021
Status verified
Apr 2026
Primary completion
Mar 31, 2027
Completion
Sep 30, 2027

Study Design

Enrollment
330 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Group A
    * 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)
  • Experimental: Group B
    * 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.
  • Experimental: Group C
    * 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.
  • Experimental: Group D
    * 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.

Primary Outcome Measure

Audiogram [ Time Frame: From diagnosis through study completion, an average of 1 year ]

Central Contacts

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