PBTC-022: PHASE II STUDY OF BEVACIZUMAB PLUS IRINOTECAN (CAMPTOSAR)

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a phase II study of the investigational agent bevacizumab combined with the conventional chemotherapy irinotecan in children with recurrent brain tumors called malignant gliomas and diffuse brain stem gliomas. Treatment failure is frequently mediated by drug resistance. A treatment that may have worked at first does not work with a second attempt. Novel strategies are required for improving outcomes. Tumor angiogenesis (blood vessel formation) plays a major role in tumor growth, invasion, and metastasis. A protein called Vascular Endothelial Growth Factor (VEGF) is a major mediator of angiogenesis and is often found in brain tumors. The drug called bevacizumab is an antibody that is a specific inhibitor of VEGF and has been shown in pre-clinical and clinical studies to be safe and useful in controlling tumor growth by itself, or in combination with standard chemotherapy. The combination of bevacizumab plus chemotherapy is expected to have a synergistic effect in tumor control. Randomized phase III studies in adults have demonstrated that such a combination improves tumor response rates and survival. Phase I studies have shown bevacizumab to be safe when used in children with recurrent solid tumors. A phase II study of bevacizumab plus irinotecan was conducted in adults with recurrent malignant glioma and demonstrated a 63% objective response rate and prolongation of progression-free survival. Hence, a phase II study of bevacizumab plus irinotecan is needed in children with recurrent malignant glioma and diffuse brain stem glioma to assess objective response rates, survival, and toxicity of this combination.