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

Not Recruiting

Trial ID: NCT00980460


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.

Official Title

Treatment of Children With All Stages of Hepatoblastoma With Temsirolimus (NSC#683864) Added to High Risk Stratum Treatment

Stanford Investigator(s)


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

   - 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

   - 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


procedure: therapeutic conventional surgery

drug: cisplatin

drug: doxorubicin hydrochloride

drug: fluorouracil

drug: irinotecan hydrochloride

drug: vincristine sulfate

procedure: liver transplantation

other: laboratory biomarker analysis

drug: temsirolimus

drug: Dexrazoxane

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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