Title
The "Head Start 4" Protocol Newly Diagnosed Children (Less than 10 Years Old) with Medulloblastoma and Other Central Nervous System Embyonal Tumors

Description
The 5 chemotherapy drugs used in the Induction part of treatment are vincristine (given over a few minutes through the central line), cisplatin (given as an infusion over 6 hours through the central line), cyclophosphamide (given as an infusion over 1 hour through the central line), etoposide (given as an infusion over 2 hours through the central line) and high-dose methotrexate (given as an infusion over 4 hours through the central line). Following recovery from the third cycle of Induction chemotherapy, about 9 to 12 weeks after starting the chemotherapy, your child will undergo repeat MRI scans of the brain and spine, as well as a repeat lumbar puncture. If these tests find no obvious signs of remaining tumor, then your child will be considered to have achieved a complete remission from the cancer. This does not mean cure. The tests are not a microscope that can see all remaining cancer cells, and we know that such cancer cells do remain. If treatment was stopped at this time point, your child's tumor would almost certainly grow back within a very few months. However, in this treatment plan, those children who have achieved a complete remission after 3 cycles of Induction chemotherapy will proceed directly to the Consolidation treatment. If these tests find obvious signs of remaining tumor, we will discuss with you whether surgery might be possible to completely remove any residual tumor before continuing with Consolidation treatment. Otherwise, children with remaining (residual) tumor after 3 cycles will receive two additional Induction chemotherapy cycles, for about 6 to 8 weeks, using the same drugs, before going on to receive the Consolidation treatment. The chemotherapy given during the Consolidation phase is marrow ablative (intense) and your child will receive re-infusion of blood cells (collected during Induction part) after the chemotherapy. The three drugs to be used in this research study are thiotepa, etoposide and carboplatin. These drugs will be given over 6 days to help kill the cancer cells. After 72 hours from getting these drugs, your child's own, previously collected and frozen blood cells will be thawed and returned through their central line.

Objective
The standard approach to the treatment of these brain tumors in young children may include surgery, radiation therapy to the brain and spinal cord and chemotherapy. Radiation therapy is the use of high energy x-rays to kill cancer cells. Chemotherapy means treatment with cancer killing drugs.
This research study will compare two different treatment regimens to see which is better for treating your child's type of brain cancer.

Treatment This research study has two parts. The first part of the study is called Induction. During Induction, a test will be done on your child's tumor for biologic and genetic markers that will help us to know how to best treat your child on this research study. Your child will be given either 3 cycles or 5 cycles of chemotherapy. Your child will also have a procedure performed called leukapheresis in which some of his/her own blood cells are collected and stored for later use. The second part of the research study is called Consolidation. Based on the results of the tumor marker tests discussed above, your child may receive either a single cycle of Consolidation drug therapy or, your child may be randomized to either a single or multiple (three) cycles of Consolidation drug therapy. If your child will be randomized, the treatment he/she will receive (single or multiple consolidation cycles) is decided by a process called randomization. Randomization means that the treatment is assigned based on chance.

Key Eligibility

• Patients must be less than 10 years of age at the time of definitive confirmatory eligible histologic or cytological diagnosis of eligible CNS tumor within the brain or spinal cord, who have not previously received either irradiation or chemotherapy. This includes medulloblastomas and CNS embryonal tumors


• Children must commence Induction chemotherapy within 28 days of the most recent definitive surgical procedure and within 21 days of the most recent neuro-imaging studies and and lumbar CSF cytological examination

Applicable Disease Sites
Brain/Central Nervous System

Participating Institutions
UW Health University Hospital