Clinical trial · Interventional
Risk-Based Therapy in Treating Younger Patients With Newly Diagnosed Liver Cancer
Treatment of Children With All Stages of Hepatoblastoma With Temsirolimus (NSC#683864) Added to High Risk Stratum Treatment
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This phase III trial studies the side effects and how well risk-based therapy works in treating younger patients with newly diagnosed liver cancer. Surgery, chemotherapy drugs (cancer fighting medicines), and when necessary, liver transplant, are the main current treatments for hepatoblastoma. The stage of the cancer is one factor used to decide the best treatment. Treating patients according to the risk group they are in may help get rid of the cancer, keep it from coming back, and decrease the side effects of chemotherapy.
Conditions
Conditions (4)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| PRETEXT I Hepatoblastoma | PRETEXT I Hepatoblastoma | ONTOLOGY_EXACT | 0.98 |
| PRETEXT II Hepatoblastoma | PRETEXT II Hepatoblastoma | ONTOLOGY_EXACT | 0.98 |
| PRETEXT III Hepatoblastoma | PRETEXT III Hepatoblastoma | ONTOLOGY_EXACT | 0.98 |
| PRETEXT IV Hepatoblastoma | PRETEXT IV Hepatoblastoma | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (10)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Cisplatin | Drug | Cisplatin | ALIAS |
| Dexrazoxane | Drug | — | UNRESOLVED |
| Doxorubicin Hydrochloride | Drug | Doxorubicin | ALIAS |
| Fluorouracil | Drug | Fluorouracil | ALIAS |
| Irinotecan Hydrochloride | Drug | Irinotecan | ALIAS |
| Laboratory Biomarker Analysis | Other | — | UNRESOLVED |
| Liver Transplantation | Procedure | — | UNRESOLVED |
| Temsirolimus | Drug | Temsirolimus | ALIAS |
Design
Arms and outcomes
Arms (5)
- type
- EXPERIMENTAL
- label
- High-risk group (regimen H)
- description
- Patients receive up front VIT chemotherapy comprising vincristine sulfate IV over 1 minute on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5, and temsirolimus IV over 30 minutes on days 1 and 8. Treatment with VIT repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 4 courses of VIT in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity. Patients undergo tumor resection or liver transplant after course 4 of C5VD followed by 2 courses of adjuvant C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6.
- interventionNames
- Drug: Cisplatin
- Drug: Doxorubicin Hydrochloride
- Drug: Fluorouracil
- Drug: Irinotecan Hydrochloride
- Other: Laboratory Biomarker Analysis
- Procedure: Liver Transplantation
- Drug: Temsirolimus
- Procedure: Therapeutic Conventional Surgery
- Drug: Vincristine Sulfate
- type
- EXPERIMENTAL
- label
Eligibility
Eligibility (as posted)
- Sex
- All
- Maximum age
- 21 Years
Show eligibility criteria text
Inclusion Criteria:
* Patients must be newly diagnosed with histologically-proven hepatoblastoma
* In emergency situations 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 on AHEP0731 without a biopsy
* Clinical situations in which such emergent treatment may be indicated include, but are not limited to, the following circumstances:
* Anatomic or mechanical compromise of critical organ function by tumor (e.g., respiratory distress/failure, abdominal compartment syndrome, urinary obstruction, etc)
* Uncorrectable coagulopathy
* For a patient to maintain eligibility for AHEP0731 when emergent treatment is given, the following must occur:
* The patient must have a clinical diagnosis of hepatoblastoma, including an elevated alpha fetoprotein, and must meet all AHEP0731 eligibility criteria at the time of emergent treatment
* Patient must be enrolled on AHEP0731 prior to initiating protocol therapy; a patient will be ineligible if any chemotherapy is administered prior to AHEP0731 enrollment
* If the patient receives AHEP0731 chemotherapy PRIOR to undergoing a diagnostic biopsy, pathologic review of material obtained in the future during either biopsy or surgical resection must either confirm the diagnosis of hepatoblastoma or not reveal another pathological diagnosis to be included in the analysis of the study aims
* Patients will be staged for risk classification and treatment at diagnosis using Children's Oncology Group (COG) staging guidelines
* At the time of study enrollment, the patient's treatment regimen must be identified; if the patient's primary tumor was resected prior to the day of enrollment and a blood specimen for the determination of serum alpha fetoprotein was not obtained prior to that surgery, the patient will be considered to have alpha fetoprotein of greater than 100 ng/mL for the purpose of treatment assignment; if tumor samples obtained prior to the date of enrollment were not sufficient to determine whether small cell undifferentiated (SCU) histology was present, treatment assignment will be made assuming SCU is not present in the tumor
* For patients with stage I or II disease, specimens for rapid central review have been submitted and the rapid central review diagnosis and staging must be available to be provided on the AHEP0731 eligibility case report form (CRF)
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores 0, 1, or 2; use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Patients may have had surgical resection of some or all sites of hepatoblastoma prior to enrollment
* Organ function requirements are not required for enrolled patients who are stage I, PFH and will not be receiving chemotherapy
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 OR serum creatinine based on age/gender as follows:
* 1 month to \< 6 months: 0.4 mg/dL
* 6 months to \< 1 year: 0.5 mg/dL
* 1 to \< 2 years: 0.6 mg/dL
* 2 to \< 6 years: 0.8 mg/dL
* 6 to \< 10 years: 1 mg/dL
* 10 to \< 13 years: 1.2 mg/dL
* 13 to \< 16 years: 1.5 mg/dL (male) or 1.4 mg/dL (female)
* \>= 16 years: 1.7 mg/dL (male) or 1.4 mg/dL (female)
* Total bilirubin \< 1.5 x upper limit of normal (ULN) for age
* Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 10 x ULN for age
* Absolute neutrophil count (ANC) \> 750/uL
* Platelet count \> 75,000/uL
* Shortening fraction \>= 27% by echocardiogram
* Ejection fraction \>= 47% by radionuclide angiogram (multi gated acquisition scan \[MUGA\]); Note: the echocardiogram (or MUGA) may be done within 28 days prior to enrollment
* Serum triglyceride level =\< 300 mg/dL (=\< 3.42 mmol/L)
* Serum cholesterol level =\< 300 mg/dL (7.75 mmol/L)
* Random or fasting blood glucose within the upper normal limits for age; if the initial blood glucose is a random sample that is outside of the normal limits, then a follow-up fasting blood glucose can be obtained and must be within the upper normal limits for age
* Normal pulmonary function tests (including diffusing capacity of the lungs for carbon monoxide \[DLCO\]) if there is clinical indication for determination (e.g. dyspnea at rest, known requirement for supplemental oxygen); Note: for patients who do not have respiratory symptoms or requirement for supplemental oxygen, pulmonary function tests (PFTs) are NOT required
* Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and if seizures are well controlled
* Prothrombin time (PT) \< 1.2 x ULN
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
* Patients with stage I or II disease who do not have specimens submitted for rapid central pathology review by day 14 after initial surgical resection
* Patients that have been previously treated with chemotherapy for hepatoblastoma or other hepatoblastoma-directed therapy (e.g., radiation therapy, biologic agents, local therapy \[embolization, radiofrequency ablation, laser\]) are not eligible
* Patients who have received any prior chemotherapy are not eligible
* Patients who are currently receiving another investigational drug are not eligible
* Patients who are currently receiving other anticancer agents are not eligible
* Patients who have previously received a solid organ transplant are not eligible
* Patients who have an uncontrolled infection are not eligible
* Females who are pregnant or breast feeding are not eligible for this study
* Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
* Males and females of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method
* Patients receiving corticosteroids are not eligible; patients must have been off corticosteroids for 7 days prior to start of chemotherapy
* Patients who are currently receiving enzyme inducing anticonvulsants are not eligible
* Patients must not be receiving any of the following potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers or inhibitors: erythromycin, clarithromycin, azithromycin, ketoconazole, itraconazole, voriconazole, posaconazole, grapefruit juice or St. John's wort
* Patients who are currently receiving therapeutic anticoagulants (including aspirin, low molecular weight heparin, warfarin and others) are not eligible
* Patients who are currently receiving angiotensin-converting enzymes (ACE) inhibitors are not eligible
* Patients must not have had major surgery within 6 weeks prior to enrollment on the high risk stratum; patients with history of recent minor surgical procedures (vascular catheter placement, bone marrow evaluation, laparoscopic surgery, liver tumor biopsy) will be eligibleReferences
Publications (3)
- DERIVEDThompson PA, Malogolowkin MH, Furman WL, Piao J, Krailo MD, Chung N, Brock L, Towbin AJ, McCarville EB, Finegold MJ, Ranganathan S, Dunn SP, Langham MR, McGahren ED, Tiao GM, Weldon CB, O'Neill AF, Rodriguez-Galindo C, Meyers RL, Katzenstein HM. Vincristine/irinotecan/temsirolimus upfront window treatment of high-risk hepatoblastoma: A report from the Children's Oncology Group AHEP0731 Study Committee. Pediatr Blood Cancer. 2023 Jul;70(7):e30365. doi: 10.1002/pbc.30365. Epub 2023 Apr 19. PMID 37073741
- DERIVEDTrobaugh-Lotrario A, Katzenstein HM, Ranganathan S, Lopez-Terrada D, Krailo MD, Piao J, Chung N, Randazzo J, Malogolowkin MH, Furman WL, McCarville EB, Towbin AJ, Tiao GM, Dunn SP, Langham MR, McGahren ED, Feusner J, Rodriguez-Galindo C, Meyers RL, O'Neill AF, Finegold MJ. Small Cell Undifferentiated Histology Does Not Adversely Affect Outcome in Hepatoblastoma: A Report From the Children's Oncology Group (COG) AHEP0731 Study Committee. J Clin Oncol. 2022 Feb 10;40(5):459-467. doi: 10.1200/JCO.21.00803. Epub 2021 Dec 7. PMID 34874751
- DERIVEDKatzenstein HM, Langham MR, Malogolowkin MH, Krailo MD, Towbin AJ, McCarville MB, Finegold MJ, Ranganathan S, Dunn S, McGahren ED, Tiao GM, O'Neill AF, Qayed M, Furman WL, Xia C, Rodriguez-Galindo C, Meyers RL. Minimal adjuvant chemotherapy for children with hepatoblastoma resected at diagnosis (AHEP0731): a Children's Oncology Group, multicentre, phase 3 trial. Lancet Oncol. 2019 May;20(5):719-727. doi: 10.1016/S1470-2045(18)30895-7. Epub 2019 Apr 8. PMID 30975630