Protracted Etoposide During Induction Therapy for High Risk Neuroblastoma

Summary

High-risk neuroblastoma is an aggressive childhood cancer that shows up as a lump or mass in the belly or around the spinal cord in the chest, neck, or pelvis. Often the tumor has spread around the body to the bones or to the soft center of the bone, called the bone marrow. High-risk neuroblastoma often responds to treatment at first, but it frequently comes back and may be even more difficult to treat.

Chemotherapy (drug treatments for cancer) is usually given at high doses in short bursts (3 to 5 days) followed by a few weeks of rest and recovery. This burst and recovery is called a "cycle" and usually takes about 21 days. Some scientists and physicians have tried to give chemotherapy at lower doses for more days, called "metronomic" chemotherapy. This method of giving chemotherapy has been used to treat neuroblastoma that has failed more standard types of treatment (relapsed neuroblastoma) and has shown some promise for those patients. One of the reasons it may work is by killing the blood vessels that feed the tumor as well as killing tumor cells themselves (the way that burst chemotherapy works). We think that giving a burst of chemotherapy together with metronomic therapy may kill the tumor while decreasing the side effects that we have seen in the past.

Treatment for high risk neuroblastoma usually occurs in 3 stages: induction, consolidation, and maintenance. During the induction phase, patients will receive chemotherapy and possibly more surgery to get rid of most of the tumor cells. Most of the chemotherapy drugs during induction will be given in the standard burst method. One of the chemotherapy drugs, etoposide, will be given in lower, metronomic doses. The doctors will study how the tumors respond and the side effects patients have. After induction most childrens' tumors will have disappeared, also called remission. These children will receive the second stage of treatment called consolidation. During this stage, subjects will receive radiation treatments to the tumor and then higher doses of chemotherapy. Because of the side effects of the high doses of chemotherapy, we will collect and store some special blood cells (called hematopoietic stem cells) early in treatment and keep them frozen. After the high doses of chemotherapy, these cells will be thawed and given to the subject. . This is called hematopoietic stem cell transplant (HSCT). The final stage of treatment, called maintenance, consists of a drug taken by mouth for 6 months.

Surgery to remove large, or bulky, tumors is a standard part of treatment for high risk neuroblastoma. A few children can have their main tumor removed before chemotherapy, but most require the tumor to shrink first. Surgery has usually been scheduled for after 3 to 5 cycles of therapy, but no one really knows how quickly the tumors are ready to come out. Because chemotherapy has significant side effects that can change the risks of surgery, we will study how early surgeries to remove tumors can happen.

This study is being done to evaluate the outcomes of disease response and survival in children with high risk neuroblastoma treated on this regimen.

Conditions

• Neuroblastoma

Interventions

DRUG

Protracted Oral Etoposide

Cisplatin with Oral Protracted Etoposide for cycles 1, 2 and 4 Day 1 - 5 * Hour 0: Etoposide 50 mg/m2 po daily * Hours 1 to 7: Cisplatin 40 mg/m2 Day 6 - 14 * Etoposide 50 mg/m2 po once daily

DRUG

Doxorubicin

Given together with cyclophosphamide for cycle 3 and 5 of induction chemotherapy Day 1 and 2 * Hours 0 to 6: Cyclophosphamide 2000 mg/m2 (67 mg/kg if \< 12 kg) with Mesna 400 mg/m2 (13 mg/kg if \< 12 kg) in D5½NS 600 mL/m2 IV over 6 hours to run at 100 mL/m2/hr * Hours 6 to 6.25: Doxorubicin 37.5 mg/m2 (1.25 mg/kg if \< 12 kg) IV over 15 minutes

DRUG

IV Bolus Etoposide

Cisplatin with Bolus IV Etoposide Day 1 Hours 0 to 6: Cisplatin 40 mg/m2 Days 2, 3, 4: Hours 0 to 1: Etoposide 200 mg/m2 Hours 1 to 7: Cisplatin 40 mg/m2 Day 5: Hours 0 to 6: Cisplatin 40 mg/m2

DRUG

Cisplatin

Cycle 1, 2, and 4

DRUG

Cyclophosphamide

Cycle 3 and 5 with doxorubicin

DRUG

Mesna

Standard weight-based dosing with cyclophosphamide

DRUG

Hematopoietic Factor

Standard weight-based dosing after cycle 3 and 5 and if needed for neutropenic recovery after cycles 1,2 and 4

PROCEDURE

Primary tumor resection

Resection of primary tumor after cycle 3, 4, or 5 as clinically appropriate

Sponsors & Collaborators

• Baylor College of Medicine

  lead OTHER

Principal Investigators

• Peter Zage, MD · Baylor College of Medicine

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-03-31

Primary Completion

2009-07-31

Completion

2015-03-31

FDA Drug

Yes

Countries

• United States

Study Locations