Cyclophosphamide, Topotecan, and Bevacizumab (CTB) in Patients With Relapsed/Refractory Ewing's Sarcoma and Neuroblastoma

Summary

The purpose of this study is to find out what effects, good and/or bad treatment with a new combination of drugs, cyclophosphamide, topotecan, and bevacizumab has on the patient and their cancer.

The medications, cyclophosphamide and topotecan, are standard drugs often used together for the treatment of cancer in children with either Ewing's sarcoma or neuroblastoma.

Bevacizumab is an experimental drug called an antibody that targets a protein important in the growth of cancer cells called vascular endothelial growth factor (VEGF). VEGF is made by tumor and other surrounding cells to help make blood vessels needed for the growth and spread of cancer cells in the body. The way that bevacizumab works is to stop the cancer cells from making their own blood supply, causing the tumor to stop growing bigger or from spreading. In adult clinical trials, bevacizumab has shown promising anti-cancer activity in patients with cancer of the colon/rectum (colorectal) and breast. It has been approved by the Food and Drug Administration (FDA) for use in patients with colorectal cancer but not in cancers found in children. Bevacizumab has been tested in early clinical studies in children and has been shown to be safe.

Other goals of this study will include research tests designed to test the following changes in the patient or their cancer: to see how the body handles and breaks down bevacizumab (pharmacokinetics), to look at changes in proteins in the blood that may affect the way the cancer responds to the combination (angiogenic profile, angiogenesis associated serum biomarkers), to look at changes in genes that may affect how the cancer responds to treatment with this combination of medications (metabolic signature), and to monitor the effects of changes in the way the body grows and develops before and after bevacizumab is given.

Conditions

• Neuroblastoma
• Sarcoma

Interventions

DRUG

Cyclophosphamide, Topotecan, and Bevacizumab

The treatment schedule for this study will consist of a 21-day cycle. Dose modification will only occur with administration of the investigational agent, bevacizumab. The schedule of administration is summarized as follows. Administration of bevacizumab will precede the administration of the cyclophosphamide and topotecan by 3 days (Day - 3) to allow for vascular stabilization prior to initiation of chemotherapy. The chemotherapy backbone will consist of cyclophosphamide and topotecan administered as follows: cyclophosphamide 250 mg/m2/day IV over 30 minutes ± 5 minutes on Days 0-4 followed by topotecan 0.75 mg/m2/day IV over 30 minutes ± 5 minutes on Day 0-4 of every cycle. The dosing of cyclophosphamide and topotecan will be fixed.

Sponsors & Collaborators

• Genentech, Inc.

  collaborator INDUSTRY

• Children's Mercy Hospital Kansas City

  collaborator OTHER

• Penn State University

  collaborator OTHER

• University of Colorado, Denver

  collaborator OTHER

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  collaborator OTHER

• Phoenix Children's Hospital Center for Cancer & Blood Disorders

  collaborator UNKNOWN

• Alberta Children's Hospital

  collaborator OTHER

• MD Anderson Cancer Center Orlando

  collaborator UNKNOWN

• M.D. Anderson Cancer Center

  collaborator OTHER

• Memorial Sloan Kettering Cancer Center

  lead OTHER

Principal Investigators

• Tanya Trippett, MD · Memorial Sloan Kettering Cancer Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-12-31

Primary Completion

2018-10-31

Completion

2018-10-31

Countries

• United States
• Canada

Study Locations