Introduction

This family protocol summary provides a general overview of the Children's Oncology Group (COG) ACNS1123 clinical trial. A trial is another word for a study. 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.

ACNS1123 is a Phase 2 clinical trial. 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 2 trial is to learn if a new treatment works in treating a specific type of cancer and how it affects the body.

In a Phase 2 trial, patients with a specific type of cancer receive a new treatment. Patients are checked for side-effects of the treatment and to see whether the cancer shrinks or goes away. The ACNS1123 study is unique in that it is not trying a new drug treatment. Instead, this study will reduce the dose and area of radiation therapy that has been used to treat germ cell tumors within the brain and spinal cord. Its aim is to reduce long-term problems from standard doses of radiation therapy, thereby increasing long-term quality of life. The study committee feels that doing this will not decrease the current cure rate.

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 your 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

ACNS1123

Official Title

Phase 2 Trial of Response-Based Radiation Therapy for Patients with Localized Central Nervous System Germ Cell Tumors (CNS GCT)

Trial Opening Date

ACNS1123 opened on May 29, 2012. The ACNS1123 study committee hopes to enroll a total of 248 patients - 125 patients on Stratum 1 and 123 patients on Stratum 2. It is expected that this study will remain open to enrollment for a total of 7 years.

Trial Closing Date

This study has been closed to accrual as of December, 2016.

General Patient Eligibility

• Age: 3 - 21 years
• Diagnosis:
  • Localized CNS non-germinomatous germ cell tumor
  • Localized CNS germinoma

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

General Background and Study Goal

Primary intracranial germ cell tumors (GCTs) represent 3-5% of all central nervous system (CNS) tumors. Approximately two-thirds of intracranial GCTs are germinomas and the remaining one-third are non-germinomatous germ cell tumors (NGGCTs). The treatment for each type of germ cell tumor is different. In this study, NGGCTs will be treated on stratum 1 and germinomas will be treated on stratum 2.

In the past, both NGGCT and germinomas were treated with radiation therapy to the entire brain and spine, called craniospinal irradiation (CSI), with additional irradiation (called a “boost”) to the tumor site. However, irradiation to the whole brain and spine can cause significant long-term problems. ACNS1123 aims to reduce the long-term problems associated with CSI in children and adolescents with localized germ cell tumors in the CNS. Localized means the tumor has not spread to other areas of the brain or spine.

Radiation therapy is measured by dose and volume. The dose of radiation therapy refers to the amount of radiation energy absorbed by the body. The irradiation volume refers to the total area of treatment. This study will treat germ cell tumors with radiation therapy to the tumor site as well as to the ventricles within the brain (whole ventricular irradiation - WVI) instead of whole brain and spine irradiation. The ventricles are the fluid filled spaces in the brain.

Stratum 1: NGGCT: the current standard of treatment for children and adolescents with NGGCT is chemotherapy to shrink the tumor followed by CSI, with additional irradiation (boost) to the tumor site. Recent studies have shown that certain patients with NGGCT can be cured with a lower dose and lower volume of irradiation to the brain and no irradiation to the spine. This study intends to treat patients initially with chemotherapy, evaluate the response, and then treat eligible patients with radiation therapy to the whole ventricles and the tumor site instead of the whole brain and whole spine.

Stratum 2: Germinoma: the standard treatment for intracranial germinoma is CSI followed by a boost to the primary tumor site. Recent studies have not given spinal irradiation and instead used whole brain irradiation (WBI) or whole ventricular irradiation (WVI) followed by additional irradiation (boost) to the primary tumor, with excellent responses. This study intends to treat patients with chemotherapy first, evaluate the tumor response, and then treat patients with lower doses of irradiation to the whole ventricles and the tumor site instead of the whole brain and whole spine.

Another goal of this study is to learn about the thinking, learning, and behavioral functioning of children and young adults being treated for newly diagnosed localized CNS germ cell tumors. To study this, patients will also be enrolled on another study: ALTE07C1.

Summary of the Treatment

Stratum 1: Patients with NGGCTs
The initial treatment is called induction. Patients will receive 6 cycles of treatment using the chemotherapy drugs carboplatin and etoposide and ifosfamide. The length of Induction is approximately 18 weeks. Following induction therapy, tumor response will be evaluated with MRI, blood tests and spinal fluid.

Patients who have had complete disappearance or partial shrinkage of their tumor and blood and spinal fluid tests that do not show elevated tumor markers will begin radiation therapy. Radiation dose is 30.6 Gy to the whole ventricle (WVI) with a 23.4 Gy boost to only those areas of the brain involved by tumor.

Those patients who still have tumor present after Induction chemotherapy will have a “second-look” surgery. If tumor is removed surgically, and biopsy shows non-active disease, these patients will also go on to receive radiation therapy.

Stratum 2: Patients with germinoma
The initial treatment is called induction. Patients will receive 4 cycles of treatment using the chemotherapy drugs carboplatin and etoposide. The length of Induction is approximately 12 weeks. Following induction therapy, tumor response will be evaluated with MRI, blood tests and spinal fluid.

Patients who have had complete or partial disappearance of their tumor will begin radiation therapy. Radiation dose is 18 Gy to the whole ventricle (WVI) with a 12 Gy boost to only those areas of the brain involved by tumor, called involved-field radiation therapy (IFRT).

Depending on the tumor response, doctors may recommend a “second-look” surgery for some patients who still have tumor present after chemotherapy. If tumor is removed surgically, and biopsy shows non-active disease, these patients will also go on to receive radiation therapy.

Special Considerations

• Patients enrolled on ACNS1123 must also agree to enroll on another study: ALTE07C1. You will be asked to sign a separate consent form for ALTE07C1. You can find a summary of this study on https://www.childrensoncologygroup.org/index.php/alte07c1
• The overall goal of ALTE07C1 is to learn about the neuropsychological (for example, thinking, learning, and remembering) and behavioral functioning of children being treated for cancer.
• Radiation Therapy (RT) can only be delivered at COG approved radiation therapy facilities.

Risks and Side Effects

Chemotherapy and radiation therapy 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 Chairs

Ute Bartels, MD
Hospital for Sick Children
Toronto, ON

Girish Dhall, MD
Children's Hospital Los Angeles
Los Angeles, CA

FAMILY PROTOCOL SUMMARY REVIEW/APPROVALS