This family protocol summary is about the Children’s Oncology Group study AHEP0731. It tells who is eligible and gives basic information about the study. More details about the study are in the consent form. You can get this from your oncologist.

AHEP0731 is a Phase III clinical trial. A trial is another word for a study. This study (clinical trial) is a therapeutic clinical trial. That means it is done to learn about treatment - its safety and how well it works. The purpose of a Phase III trial is to learn if a drug or treatment that is known to work in treating a type of cancer is better in some way than the standard treatment. For example, does it have better cure rates, longer control of disease, fewer or less serious side effects, or fewer days in the hospital?

AHEP0731 compares several different treatments. These treatments are called study arms. Usually, one study arm is the standard or the best proven current treatment. The other study arms have some changes or additions. The new treatment is thought to be at least as good as the standard treatment. It is not known if the new treatment will be better than the standard treatment.

In a Phase III trial, each child is assigned to a study arm by a method called randomization. This is a process like flipping a coin that assures that each child has a fair and equal chance of being assigned to any of the study arms. This way the study arms can be compared fairly.

In most clinical trials, we will not know which treatment is better until all of the children taking part in the trial have completed treatment and have been getting checked for several years. If one of the treatments is found to be better or safer than the others while the trial is still going on, the trial will be stopped. All children still in the trial will be given the treatment with the best results when possible.

It is important to understand that participating in a clinical trial is entirely voluntary. The decision about whether or not to participate will not affect the care provided by the health care team in any way. You can find additional information about participation in clinical trials at Always discuss any questions that you may have with your health care team.

Study Number


Study Title

Treatment of Children with All Stages of Hepatoblastoma with Temsirolimus Added to High Risk Stratum Treatment

Study Opening Date

AHEP0731 opened on 9/14/09. The committee hopes to enroll 240 patients. Patients will be treated in 4 different groups (stratums).

  • Stratum 2 closed on May 28, 2014 because the number of patients needed for the study had been enrolled
  • Stratum 3 closed on March 12, 2012 because the number of patients needed for the study had been enrolled
  • Stratum 4 reached accrual goals and temporarily closed on 6/30/16 for assessment and then reopened on 7/29/16

General Patient Eligibility

  • Age: 21 years old or youger
  • Diagnosis: Newly diagnosed Hepatoblastoma

Please consult your doctor to determine whether you or your child may participate in this study.

General Background and Study Goal

Hepatoblastoma is the most common cancer of the liver in children. When the tumor can be surgically removed, surgery alone has been very successful in curing hepatoblastoma. In children whose tumor cannot be surgically removed or has spread to other areas of the body (metastasized) hepatoblastoma can be harder to cure. For those patients, surgery, chemotherapy drugs (cancer fighting medicines) and for some patients, liver transplant have been used to treat hepatoblastoma.

Specific features of hepatoblastoma have been used to predict how children will respond to therapy. These features include:

  • If all the tumor can be completely removed by surgery
  • If the tumor cells have spread to other parts of the body
  • How the tumor cells look under the microscope
    • Hepatoblastoma can be made up of many different types of cells. Tumors made up of only "pure fetal" cells (PFH) are less aggressive, and those that contain any amount of "small cell undifferentiated" (SCU) cells may be harder to cure
  • AFP (alpha-fetoprotein) levels
    • AFP is a protein that is secreted by hepatoblastoma tumors, and is measured with a blood test. A low level of AFP at diagnosis can indicate that the tumor may be harder to cure and may benefit from more therapy.

Summary of the Treatment

All patients will be assigned to a risk group based on tumor type, staging, and AFP level.

  • Very Low Risk/Stratum 1
    • tumor is completely removed by surgery (Stage 1) AND
    • tumor is composed of only one type of tumor cell called pure fetal histology (PFH)
  • Low Risk/Stratum 2
    • tumor is not completely removed by surgery, but only a very small amount of tumor cells left in the body (Stage 2) OR
    • tumor is completely removed by surgery but not all the tumor cells are PFH. Tumor with SCU cells cannot be treated on this stratum.
  • Intermediate Risk/Stratum 3
    • Tumor is not completely removed by surgery and there is a larger amount of tumor left in the body (Stage 3) OR
    • Tumor spread to the lymph nodes in the abdomen (even if all the tumor is removed) OR
    • Tumor is Stage 1-3, but contains small cell undifferentiated (SCU) cells.
      • SCU cells are more aggressive and need more intensive treatment even if the tumor is completely removed.
  • High Risk/Stratum 4
    • Tumor is not completely removed by surgery and has spread outside of the abdomen OR
    • Any stage tumor with a low AFP level.

On this study, the treatment of Hepatoblastoma is based on the risk group:

  • Very Low Risk/ Stratum 1
    • Surgery only
  • Low Risk/ Stratum 2
    • Surgery
    • 2 cycles of C5V Chemotherapy
      • Cisplatin, 5-fluorouracil and Vincristine
        • 1 cycle of chemotherapy lasts 21 days
  • Intermediate Risk/Stratum 3
    • 6 cycles of C5VD
      • Cisplatin, 5-fluorouracil, Vincristine and Doxorubicin
        • 1 cycle of chemotherapy lasts 21 days
    • Surgery/transplant
      • Some children may have a liver transplant
  • High Risk/Stratum
    • 2 cycles of VIT Chemotherapy (Vincristine, Irinotecan, Temsirolimus **)
    • Further treatment will be based on tumor response after 2 cycles of chemotherapy
      • Patients who have a good response to the 2 cycles of VIT will receive 6 additional cycles of C5VD and 2 additional cycles of VIT in addition to surgery
        • Some children may have a liver transplant
      • Patients who do not have a good response to the 2 cycles of VIT will receive 6 additional cycles of C5VD and surgery
        • Some children may have a liver transplant

**In October 2014, the study was amended to add the drug Temsirolimus to vincristine and irinotecan for high risk patients.

Special Considerations

Patients classified as Very Low and Low Risk will have their tumor centrally evaluated prior to study enrollment.

Risks and Side Effects

Chemotherapy can cause side effects during and after treatment. All patients will be closely monitored for possible side effects of the medicines. All risks and side effects will be explained by your treatment team during the consent process. They can answer any questions that you may have about giving permission for your child to be in the clinical trial or other aspects of care. Please refer to the consent form for a detailed explanation of the side effects associated with the treatment on this study

Contact Information

Your child's oncologist and nurses are the best sources for further information.

Study Chair

Howard Katzenstein MD


Initial development Name Date
Written by Christie Powell February 28, 2012
Reviewed/approved by (PI) Howard Katzenstein MD June 23, 2016
Ongoing review
Reviewed and updated by Elizabeth Bell January 26, 2016
Christie Powell, CRNP February 8, 2017
February 6, 2018