Introduction

This family protocol summary provides a general overview of the Children's Oncology Group ANBL1232. It tells who is eligible and gives basic information about the study. More details about the study are in the consent form and protocol. You can get these from your oncologist.

ANBL1232 is a Phase 3 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 more about how well treatments work and the side effects of the treatments. The purpose of a Phase 3 trial is to learn if a new 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?

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 followed for several years. If one of the treatments is found to be better or safer than the others while the trial is still on-going, 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 www.childrensoncologygroup.org. Always discuss any questions that you may have with your health care team.

Study Number

ANBL1232

Study Title

Utilizing Response and Biology Based Risk Factors to Guide Therapy in Patients with Non-High Risk Neuroblastoma

Study Opening Date

ANBL1232 opened on 7/28/2014. The study team plans to enroll up to 621 patients. It is expected that this study will remain open until the summer of 2019.

General Patient Eligibility

There are 3 groups of patients who are eligible for treatment on this protocol:

Group A:

• Less than 12 months of age at the time of diagnosis
• The tumor is located only in one place and has not spread
• The tumor size is less than 5 centimeters (about 2 inches) from side to side
• No prior surgery or biopsy of the tumor

Group B:

• Less than 18 months of age at the time of diagnosis
• No surgery to remove the tumor, only biopsy
• The tumor is not causing any symptoms or problems to other organs
• The tumor is made up of "favorable" biology features. "Favorable" or "unfavorable" biology features are certain characteristics of the tumor cells determined with special tests in the laboratory.

Group C:

• Less than 18 months of age at the time of diagnosis
• The tumor is in more than one place, but involves only specific organs (liver, skin, bone marrow)

Some patients may also have the following risk factors:

• The tumor involves the liver, causing the liver to be large
• The tumor is causing symptoms
• The tumor is made up of "unfavorable" biology features

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

General Background and Treatment

The goal of this study is to see if non-high-risk neuroblastoma can be treated without surgery or by changing the amount of chemotherapy given and still get very good results.

Group A

Standard therapy for Group A patients in the past would be surgery to take the tumor out. Recent studies have shown that these tumors will often become smaller or completely go away on their own without surgery.

In this study:

• No surgery or other treatments will be planned
• Children will be closely observed for 96 weeks (about 2 years) with frequent tests and scans to look for any signs that the cancer has grown or spread to other parts of the body
• If at any time during the 96 week period the tumor grows or the cancer spreads, then your child will stop taking part in the trial and your doctor will discuss treatment options with you. Surgery may be recommended.

Group B

Standard therapy for Group B patients in the past would be to start chemotherapy and/or perform surgery to remove the tumor.

In this study:

• Scans will be done 8 weeks after diagnosis to check tumor size and look for signs of tumor spread.
  • If the tumor does not get bigger and the cancer does not spread, these patients will be observed for 3 years.
  • If the tumor gets bigger, patients will be given chemotherapy and/or have surgery
    • Chemotherapy will be given in blocks of 2 cycles and patients can get up to 8 cycles in total. After every 2 cycles there will be tests and scans to see if the tumor is getting smaller.
      • If the tumor gets at least 50% smaller, chemotherapy will stop and the patient will be observed with tests and scans for up to 3 years after finishing chemotherapy.
      • If the tumor does not get smaller or spreads, treatment will stop and your doctor will discuss other treatment options.
  • If the cancer spreads at any time during this study, treatment on this trial will stop and the doctor will discuss treatment options.

Group C

Standard therapy for Group C patients depends on whether or not they have symptoms, and whether the tumor cells have "favorable" or "unfavorable" biology features.

It is standard for patients without symptoms and with "favorable" biology features to be observed without treatment. It is standard for patients with symptoms or with "unfavorable" biology features to be given chemotherapy. The amount of chemotherapy given depends on the tumor response to therapy.

Recent studies show that very young patients whose cancer involves the liver or who have symptoms caused by the cancer have a higher chance of having complications. In this study, we hope that by starting chemotherapy immediately for these patients, we can prevent the complications and get better results.

A symptom score system will be used to decide on the timing and amount of chemotherapy given. The scoring system will help improve treatment since the amount of chemotherapy given will be decided by the patient's response to therapy and their own symptom score.

In this study:

• Patients will NOT get chemotherapy immediately but will be closely observed for 3 years with tests and scans if they:
  • do not have symptoms, and
  • have "favorable" tumor cells

• Patients will get chemotherapy treatment immediately and the scoring system will be used to decide when to stop chemotherapy if they:
  • are less than 3 months old and have a tumor that involves the liver,
  • have symptoms at diagnosis, or
  • have "unfavorable" tumor cell biology

• If symptoms develop while being observed, the scoring system will be used to decide when to start and stop chemotherapy:
  • Chemotherapy will begin if the patient reaches a symptom score of 2 or more
• If the primary tumor (tumor that is the source of all of all other tumor locations) grows more than 25% while patients are being observed, further therapy will be started:
  • Chemotherapy would be started if the primary tumor is larger and not easily removed with surgery.
  • Surgery may be considered for smaller tumors (originally less than 5 cm (2 inches) in diameter), or the patient may continue to be observed.

The amount of chemotherapy given depends on how well the tumor responds to therapy and if symptoms go away. The use of the symptom score is to see if we can give a more personalized amount of chemotherapy.

• Chemotherapy will be given in blocks of 2 cycles and patients may get up to 8 cycles total
  • If the tumor responds well (tumor is at least 50% smaller and symptom score is 0), then patients will go back to being closely observed for up to 3 years after finishing chemotherapy.
  • If the tumor does not respond well, treatment on this trial will stop and the doctor will discuss other treatment options.

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

FAMILY PROTOCOL SUMMARY REVIEW/APPROVALS