Introduction

This family protocol summary provides a general overview of the Children's Oncology Group (COG) study ANBL1221. It explains 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

ANBL1221 is a Phase 2 clinical trial. A trial is another word for a study. This study (clinical trial) is a therapeutic clinical trial. The purpose of a Phase 2 trial is to learn if a new treatment works in treating a specific type of cancer and how it affects the body. That means it is done to learn more about how well treatments work and the side effects of the treatments.

In a Phase 2 trial, patients with a specific type of cancer receive a new treatment using a dose that was found to be safe in a Phase I trial. Patients are checked for side effects of the treatment and to see whether the cancer shrinks or goes away.

Phase 2 are offered to patients whose disease has not responded to other treatments or to patients whose disease doesn't have a standard treatment. Phase 2 trials may be offered to patients with the type of disease that responded well in Phase I trials.

In this study, each child was 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 makes sure the study arms can be compared fairly. The randomization process is described in the COG Family Handbook for Children with Cancer.

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

ANBL1221

Official Title

A Phase 2 Randomized Trial of Irinotecan/Temozolomide with Temsirolimus or Chimeric 14.18 Antibody (ch14.18) in Children with Refractory, Relapsed or Progressive Neuroblastoma

Study Opening Date

ANBL1221 opened on February 4, 2013 with a plan to enroll up to 74 patients. It was temporarily closed on March 27, 2015 for a scheduled review. Upon review, too few patients treated on Regimen A responded to therapy and so this regimen was closed. The study reopened on 8/1/16 with all patients then being enrolled on Regimen B.

Study Closing Date

The study closed on 11/20/17 and there are no final results yet to report; this is because it has been too short of a time to review all the information.

General Patient Eligibility

• All ages were eligible
• Diagnosis: Neuroblastoma that has returned for the first time, progressed or has become resistant after 4 cycles of conventional therapy
• Neuroblastoma must be measureable by CT/MRI, or positive by MIBG/PET imaging, or confirmed by biopsy.

General Background and Study Goal

New ways to treat patients with neuroblastoma that has not responded to primary treatment or has returned are needed. Targeted therapies are increasingly being used in the treatment of cancer. This trial set out to compare two molecularly targeted medications given along with chemotherapy. Targeted therapies are different from standard chemotherapy in that they act on specific cancer molecules to block their growth and spread, without destroying nearby healthy cells. Temsirolimus and ch14.18 are the targeted therapies used in this protocol. Both medications have been used in children with neuroblastoma and have shown promising benefits.

All patients who are part of this study were treated with temozolomide and irinotecan. Their use in combination with the targeted agents will determine if one targeted therapy agent has an improved response rate or has fewer side effects than the other agent. Half of the patients will receive ch14.18 and half will receive temsirolimus. The results of this study will help researchers select which targeted therapy agents should be used in future studies.

Summary of the Treatment

This study was initially a randomized study looking at two different targeted agents in combination with a standard relapsed neuroblastoma regimen of irinotecan and temozolomide.

• Regimen A patients received irinotecan, temozolomide and temsirolimus
• Regimen B patients received irinotecan, temozolomide and ch14.18.

Patients on Regimen B also received a medication called GM-CSF. Prior studies have shown that GM-CSF and ch14.18 work better together than ch14.18 alone.

Treatment cycles are given every 21 days. Tumor response will be assessed following cycle 2, 4, and 6, and then every 4 cycles until therapy is completed. Treatment can continue for up to 17 cycles, about 1 year.

Special Considerations

• Temozolomide must be taken on an empty stomach as its absorption is affected by food
• Irinotecan can cause diarrhea so an antibiotic will be prescribed for ten days every cycle, 2 days before, during, and 3 days after the irinotecan.
• For patients assigned to Regimen B: Ch14.18 is given continuously through the IV and requires several days of hospitalization
• For patients assigned to Regimen B, GM-CSF is given as a subcutaneous injection for 7 days during each cycle.

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

Rajen Mody, MD, MS
CS Mott Children’s Hospital
Ann Arbor, MI

FAMILY PROTOCOL SUMMARY REVIEW/APPROVALS