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NCT00980460 · CITED IN SOURCE DOCUMENTS

Risk-Based Therapy in Treating Younger Patients With Newly Diagnosed Liver Cancer

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2026-06-30

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

Who could take part
eligibility Criteria
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 eligible
healthy Volunteers
false
maximum Age
21 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. 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.
    intervention Names
    1. Drug: Cisplatin
    2. Drug: Doxorubicin Hydrochloride
    3. Drug: Fluorouracil
    4. Drug: Irinotecan Hydrochloride
    5. Other: Laboratory Biomarker Analysis
    6. Procedure: Liver Transplantation
    7. Drug: Temsirolimus
    8. Procedure: Therapeutic Conventional Surgery
    9. Drug: Vincristine Sulfate
    label
    High-risk group (regimen H)
    type
    EXPERIMENTAL
  2. description
    (regimen W replaced by regimen H as of Amendment 3B) Patients receive up front VI chemotherapy comprising vincristine sulfate IV on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5. Treatment with VI 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 1 courses of VI 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.
    intervention Names
    1. Drug: Cisplatin
    2. Drug: Doxorubicin Hydrochloride
    3. Drug: Fluorouracil
    4. Drug: Irinotecan Hydrochloride
    5. Other: Laboratory Biomarker Analysis
    6. Procedure: Therapeutic Conventional Surgery
    7. Drug: Vincristine Sulfate
    label
    High-risk group (regimen W)
    type
    EXPERIMENTAL
  3. description
    Patients receive C5VD chemotherapy comprising cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, vincristine sulfate IV over 1 minute on days 2, 9, and 16, and doxorubicin hydrochloride IV over 15 minutes on days 1-2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo surgical resection after course 2 OR surgical resection or liver transplantation after course 4 of C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6. (Closed to accrual as of 3/12/2012)
    intervention Names
    1. Drug: Cisplatin
    2. Drug: Dexrazoxane
    3. Drug: Doxorubicin Hydrochloride
    4. Drug: Fluorouracil
    5. Other: Laboratory Biomarker Analysis
    6. Procedure: Liver Transplantation
    7. Procedure: Therapeutic Conventional Surgery
    8. Drug: Vincristine Sulfate
    label
    Intermediate-risk group (regimen F)
    type
    EXPERIMENTAL
  4. description
    Patients undergo surgery and then receive adjuvant cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, and vincristine sulfate IV over 1 minute on days 2, 9, and 16. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
    intervention Names
    1. Drug: Cisplatin
    2. Drug: Fluorouracil
    3. Other: Laboratory Biomarker Analysis
    4. Procedure: Therapeutic Conventional Surgery
    5. Drug: Vincristine Sulfate
    label
    Low-risk group (regimen T)
    type
    EXPERIMENTAL
  5. description
    Patients undergo surgery and then receive no further treatment.
    intervention Names
    1. Other: Laboratory Biomarker Analysis
    2. Procedure: Therapeutic Conventional Surgery
    label
    Very low-risk group
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. High-risk group (regimen H)
    2. High-risk group (regimen W)
    3. Intermediate-risk group (regimen F)
    4. Low-risk group (regimen T)
    description
    Given IV
    name
    Cisplatin
    other Names
    1. Abiplatin
    2. Blastolem
    3. Briplatin
    4. CDDP
    5. Cis-diammine-dichloroplatinum
    6. Cis-diamminedichloridoplatinum
    7. Cis-diamminedichloro Platinum (II)
    8. Cis-diamminedichloroplatinum
    9. Cis-dichloroammine Platinum (II)
    10. Cis-platinous Diamine Dichloride
    11. Cis-platinum
    12. Cis-platinum II
    type
    DRUG
  2. arm Group Labels
    1. Intermediate-risk group (regimen F)
    description
    Given IV
    name
    Dexrazoxane
    other Names
    1. 2, 6-Piperazinedione, 4,4'-propylenedi-, (P)- (8CI)
    2. 2,6-Piperazinedione, 4, 4'-(1-methyl-1,2-ethanediyl)bis-, (S)- (9CI)
    3. ADR 529
    4. ADR-529
    5. ADR529
    6. ICRF 187
    7. ICRF-187
    8. ICRF187
    9. Razoxane (+)-form
    10. Soluble ICRF (L-isomer)
    type
    DRUG
  3. arm Group Labels
    1. High-risk group (regimen H)
    2. High-risk group (regimen W)
    3. Intermediate-risk group (regimen F)
    description
    Given IV
    name
    Doxorubicin Hydrochloride
    other Names
    1. 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
    2. ADM
    3. Adriacin
    4. Adriamycin
    5. Adriamycin Hydrochloride
    6. Adriamycin PFS
    7. Adriamycin RDF
    8. ADRIAMYCIN, HYDROCHLORIDE
    9. Adriamycine
    10. Adriblastina
    11. Adriblastine
    12. Adrimedac
    type
    DRUG
  4. arm Group Labels
    1. High-risk group (regimen H)
    2. High-risk group (regimen W)
    3. Intermediate-risk group (regimen F)
    4. Low-risk group (regimen T)
    description
    Given IV
    name
    Fluorouracil
    other Names
    1. 5 Fluorouracil
    2. 5 Fluorouracilum
    3. 5 FU
    4. 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
    5. 5-Fluorouracil
    6. 5-Fluracil
    7. 5-Fu
    8. 5FU
    9. AccuSite
    10. Carac
    11. Fluoro Uracil
    12. Fluouracil
    type
    DRUG
  5. arm Group Labels
    1. High-risk group (regimen H)
    2. High-risk group (regimen W)
    description
    Given IV
    name
    Irinotecan Hydrochloride
    other Names
    1. Campto
    2. Camptosar
    3. Camptothecin 11
    4. Camptothecin-11
    5. CPT 11
    6. CPT-11
    7. CPT11
    8. Irinomedac
    9. Irinotecan Hydrochloride Trihydrate
    10. Irinotecan Monohydrochloride Trihydrate
    11. U 101440E
    12. U-101440E
    type
    DRUG
  6. arm Group Labels
    1. High-risk group (regimen H)
    2. High-risk group (regimen W)
    3. Intermediate-risk group (regimen F)
    4. Low-risk group (regimen T)
    5. Very low-risk group
    description
    Correlative studies
    name
    Laboratory Biomarker Analysis
    type
    OTHER
  7. arm Group Labels
    1. High-risk group (regimen H)
    2. Intermediate-risk group (regimen F)
    description
    Undergo liver transplant
    name
    Liver Transplantation
    other Names
    1. Hepatic Transplantation
    2. Liver Grafting
    3. Liver Transplant
    4. Transplantation of Liver
    type
    PROCEDURE
  8. arm Group Labels
    1. High-risk group (regimen H)
    description
    Given IV
    name
    Temsirolimus
    other Names
    1. CCI 779
    2. CCI-779
    3. CCI-779 Rapamycin Analog
    4. CCI779
    5. Cell Cycle Inhibitor 779
    6. Rapamycin Analog
    7. Rapamycin Analog CCI-779
    8. Torisel
    type
    DRUG
  9. arm Group Labels
    1. High-risk group (regimen H)
    2. High-risk group (regimen W)
    3. Intermediate-risk group (regimen F)
    4. Low-risk group (regimen T)
    5. Very low-risk group
    description
    Undergo surgery
    name
    Therapeutic Conventional Surgery
    type
    PROCEDURE
  10. arm Group Labels
    1. High-risk group (regimen H)
    2. High-risk group (regimen W)
    3. Intermediate-risk group (regimen F)
    4. Low-risk group (regimen T)
    description
    Given IV
    name
    Vincristine Sulfate
    other Names
    1. Kyocristine
    2. Leurocristine Sulfate
    3. Leurocristine, sulfate
    4. Oncovin
    5. Vincasar
    6. Vincosid
    7. Vincrex
    8. Vincristine, sulfate
    type
    DRUG
Study design
allocation
NON_RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
236
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Estimated 5-year EFS where EFS is calculated as the time from study enrollment to disease progression, disease relapse, occurrence of a second malignant neoplasm, death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients without an event are censored at last contact.
    measure
    Event-free Survival
    time Frame
    Time from patient enrollment to progression, treatment failure, death from any cause, diagnosis of a second malignant neoplasm, or last follow-up, assessed up to 5 years
  2. description
    All grade 3 or 4 or greater non-hematological toxicities. The frequency of each toxicity type will be quantified as the number of reporting periods on which the toxicity of the relevant grade is reported. This measure does not apply to patients enrolled in the VERY LOW RISK group.
    measure
    Number of Cycles on Which Grade 3 or Higher Adverse Events Coded According to CTC AE Version 5 Were Observed
    time Frame
    During protocol therapy up to 1 year after enrollment
  3. description
    Number of patients who experience on-protocol-therapy death possibly, probably or likely related to systemic chemotherapy. This outcome measure applies to INTERMEDIATE RISK patients only.
    measure
    Number of Deaths
    time Frame
    During protocol therapy or within 30 days of the termination of protocol therapy up to 1 year after enrollment
  4. description
    RECIST v 1.1 and serum alphafetoprotein responses are evaluated separately. RECIST v 1.1 complete response (CR) is defined as disappearance of all target lesions and partial response (PR) is defined as reduction of at last 30% in the sum of the longest dimension of all target lesions (CR and PR measured by CT or MRI) between enrollment. Serum alphafetoprotein response is a decrease of at least 90% from the last serum alphafetoprotein measurement from the baseline prior to the start of chemotherapy to the end of cycle 2. This is calculated for HIGH RISK regimen W and HIGH RISK regimen H only.
    measure
    Disease Status at the End of 2 Courses of Therapy
    time Frame
    First two cycles of therapy- up to 42 days after enrollment
secondary Outcomes
  1. description
    A patient for whom referral is considered appropriate who receives a consultation after enrollment will be considered a success with respect to feasibility.
    measure
    Feasibility of Referral for Liver Transplantation
    time Frame
    3 cycles of therapy - up to 3 months after enrollment
Full study description
brief Summary
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.
detailed Description
PRIMARY OBJECTIVES: I. To estimate the event-free survival (EFS) in children with stage I (non-pure fetal histology \[PFH\], non-small cell undifferentiated \[SCU\]) and stage II (non-SCU) hepatoblastoma treated with surgical resection followed by 2 cycles of cisplatin, fluorouracil, and vincristine sulfate (C5V). II. To determine the feasibility and toxicity of adding doxorubicin (doxorubicin hydrochloride) to the chemotherapy regimen of C5V for children with intermediate-risk hepatoblastoma. III. To estimate the response rate to vincristine (vincristine sulfate), irinotecan (irinotecan hydrochloride), and temsirolimus in previously untreated children with high-risk, metastatic hepatoblastoma. IV. To determine whether timely (between diagnosis and end of second cycle of chemotherapy) consultation with a treatment center with surgical expertise in major pediatric liver resection and transplant can be achieved in 70% of patients with potentially unresectable hepatoblastoma. V. To foster the collection of tumor tissue and biologic samples to facilitate translational research and to provide data that may aid in risk-adapted approaches for subsequent clinical trials. SECONDARY OBJECTIVES: I. To estimate the EFS of patients with stage I PFH treated with surgery alone. II. To determine whether orthotopic liver transplantation (OLT) can be accomplished after successful referral and completion of 4 cycles of initial chemotherapy. III. To estimate the 2-year EFS for patients once identified as candidates for possible OLT, the 2-year EFS for patients referred to a transplant center that are resected without OLT, and the 2-year EFS for patients referred to a transplant center who receive OLT. IV. To register children with hepatoblastoma who receive OLT with PLUTO (Pediatric Liver Unresectable Tumor Observatory), an international cooperative registry for children transplanted for liver tumors. V. To determine if pretreatment extent of disease (PRETEXT) grouping can predict tumor resectability. VI. To monitor the concordance between institutional assessment of PRETEXT grouping and PRETEXT grouping as performed by expert panel review. VII. To estimate the proportion of stage IV patients who have surgical resection of metastatic pulmonary lesions. VIII. To determine the proportion and estimate the EFS of patients with potentially poor prognostic factors including alpha fetoprotein (AFP) \< 100 ng/mL at diagnosis, microscopic positive surgical margins, surgical complications, multifocal tumors, microscopic vascular invasion, macrotrabecular histologic subtype, and SCU histologic subtype. OUTLINE: Patients are assigned to 1 of 4 treatment groups according to risk group. VERY LOW-RISK GROUP: Patients undergo surgery and receive no further treatment. LOW-RISK GROUP: (regimen T) Patients undergo surgery and then receive adjuvant cisplatin intravenously (IV) over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, and vincristine sulfate IV over 1 minute on days 2, 9, and 16. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. INTERMEDIATE-RISK GROUP: (regimen F) (closed to accrual as of 3/12/2012) Patients receive C5VD chemotherapy comprising cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, vincristine sulfate IV over 1 minute on days 2, 9, and 16, and doxorubicin hydrochloride IV over 15 minutes on days 1-2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo surgical resection after course 2 OR surgical resection or liver transplantation after course 4 of C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6. HIGH-RISK GROUP: (regimen W) (regimen W replaced by regimen H as of Amendment 3B) Patients receive up front VI chemotherapy comprising vincristine sulfate IV on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5. Treatment with VI 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 1 courses of VI 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. HIGH-RISK GROUP: (regimen H) 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. After completion of study therapy, patients who receive chemotherapy are followed up periodically for at least 4 years.
Source references
references
  1. citation
    Thompson 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
    type
    DERIVED
  2. citation
    Trobaugh-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
    type
    DERIVED
  3. citation
    Katzenstein 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
    type
    DERIVED
see Also Links
  1. label
    Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.
Source notices and limitations
    Discovery and provenance
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      occurrences
      1. context exact
        l trials is to perform surgery initially when a complete resection can be done with a simple, negative-margin hemihepatectomy. The COG <a href="/clinicaltrials/NCT00980460">AHEP0731 (NCT00980460)</a> trial studied the use of PRETEXT and POSTTEXT to determine the optimal approach and timing of surgery. POSTTEXT imaging grouping wa
        end
        61985
        exact text
        NCT00980460
        start
        61974
      2. context exact
        surgery initially when a complete resection can be done with a simple, negative-margin hemihepatectomy. The COG <a href="/clinicaltrials/NCT00980460">AHEP0731 (NCT00980460)</a> trial studied the use of PRETEXT and POSTTEXT to determine the optimal approach and timing of surgery. POSTTEXT imaging grouping was performed after two a
        end
        62008
        exact text
        NCT00980460
        start
        61997
      3. context exact
        trast agent. If the diagnosis is in doubt, a confirmatory biopsy is done.</li><li>Children's Oncology Group (COG) surgical guidelines (<a href="/clinicaltrials/NCT00980460">AHEP0731 [NCT00980460]</a> appendix) recommend tumor resection at diagnosis without preoperative chemotherapy in children with PRE-Treatment EXTent of disease
        end
        131323
        exact text
        NCT00980460
        start
        131312
      4. context exact
        gnosis is in doubt, a confirmatory biopsy is done.</li><li>Children's Oncology Group (COG) surgical guidelines (<a href="/clinicaltrials/NCT00980460">AHEP0731 [NCT00980460]</a> appendix) recommend tumor resection at diagnosis without preoperative chemotherapy in children with PRE-Treatment EXTent of disease (PRETEXT) group I tumo
        end
        131346
        exact text
        NCT00980460
        start
        131335
      5. context exact
        ge at presentation.[<a href="#cit/section_7.53">53</a>,<a href="#cit/section_7.84">84</a>] However, in a prospective study by the COG (<a href="/clinicaltrials/NCT00980460">AHEP0731 [NCT00980460]</a>), the presence of small cell undifferentiated histology did not correlate with age, sex, or AFP levels at diagnosis.[<a href="#cit/
        end
        154452
        exact text
        NCT00980460
        start
        154441
      6. context exact
        href="#cit/section_7.53">53</a>,<a href="#cit/section_7.84">84</a>] However, in a prospective study by the COG (<a href="/clinicaltrials/NCT00980460">AHEP0731 [NCT00980460]</a>), the presence of small cell undifferentiated histology did not correlate with age, sex, or AFP levels at diagnosis.[<a href="#cit/section_7.86">86</a>]</
        end
        154475
        exact text
        NCT00980460
        start
        154464
      7. context exact
        ldren survived, and one child died of complications from transplant.[<a href="#cit/section_7.90">90</a>]</li><li>A report from the COG <a href="/clinicaltrials/NCT00980460">AHEP0731 (NCT00980460)</a> trial identified 35 of 177 evaluable patients (19%) with small cell undifferentiated hepatoblastoma confirmed by central review.[<a
        end
        158085
        exact text
        NCT00980460
        start
        158074
      8. context exact
        child died of complications from transplant.[<a href="#cit/section_7.90">90</a>]</li><li>A report from the COG <a href="/clinicaltrials/NCT00980460">AHEP0731 (NCT00980460)</a> trial identified 35 of 177 evaluable patients (19%) with small cell undifferentiated hepatoblastoma confirmed by central review.[<a href="#cit/section_7.8
        end
        158108
        exact text
        NCT00980460
        start
        158097
      9. context exact
        tabindex="-1">Approximately 20% to 30% of children with hepatoblastoma have resectable disease at diagnosis. COG surgical guidelines (<a href="/clinicaltrials/NCT00980460">AHEP0731 [NCT00980460]</a> appendix) recommend tumor resection at diagnosis without preoperative chemotherapy in children with PRETEXT I tumors and PRETEXT II
        end
        180769
        exact text
        NCT00980460
        start
        180758
      10. context exact
        ately 20% to 30% of children with hepatoblastoma have resectable disease at diagnosis. COG surgical guidelines (<a href="/clinicaltrials/NCT00980460">AHEP0731 [NCT00980460]</a> appendix) recommend tumor resection at diagnosis without preoperative chemotherapy in children with PRETEXT I tumors and PRETEXT II tumors with greater th
        end
        180792
        exact text
        NCT00980460
        start
        180781
      11. context exact
        r without microscopic margins, and postoperative chemotherapy):</p> <div class="pdq-content-list"><ol id="_649"><li>In the COG <a href="/clinicaltrials/NCT00980460">AHEP0731 (NCT00980460)</a> trial, 49 of 51 patients with stage I or stage II hepatoblastoma (without pure fetal histology) received two cycles of adjuvant che
        end
        183524
        exact text
        NCT00980460
        start
        183513
      12. context exact
        argins, and postoperative chemotherapy):</p> <div class="pdq-content-list"><ol id="_649"><li>In the COG <a href="/clinicaltrials/NCT00980460">AHEP0731 (NCT00980460)</a> trial, 49 of 51 patients with stage I or stage II hepatoblastoma (without pure fetal histology) received two cycles of adjuvant chemotherapy consisting of
        end
        183547
        exact text
        NCT00980460
        start
        183536
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        Updated: January 6, 2025
        datetime
        2025-01-06T12:00:00Z
        display
        January 6, 2025

    Preserved source evidence · Not medical advice