Cediranib, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma
Basic Trial Information
This phase I/II trial is studying the side effects and best dose of cediranib to see how well it works when given together with temozolomide and radiation therapy in treating patients with newly diagnosed glioblastoma. Cediranib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving cediranib together with temozolomide and radiation therapy may kill more tumor cells.
Further Study Information
I. To determine the safety profile and optimal dose of AZD2171 (cediranib) (15mg or 20mg or 30mg) in combination with temozolomide and radiation in patients with newly diagnosed glioblastoma (Phase Ib) II. To determine median progression-free survival of patients with newly diagnosed glioblastoma treated with AZD2171 in combination with temozolomide and radiation (Phase II)
I. To determine the radiographic response proportion in newly diagnosed glioblastoma patients with measurable disease. (Phase II) II. To determine the median overall survival. (Phase II) III. To determine the "vascular normalization" window in newly diagnosed glioblastoma patients by the application of serial, non-invasive, MRI parameters. (Phase II) IV. To measure the glucose metabolism changes in a subset of newly diagnosed glioblastoma patients by performing FDG PET studies. (Phase II) V. Measurement of circulating endothelial and progenitor cells and plasma levels of VEGF-A; VEGF-B; VEGF-C; VEGF-D; sVEGFR1, sVEGFR2, bFGF, PlGF, PDGF-AA; PDGF-AB; PDGF-BB; SDF1α; tumstatin; thrombospondin-1; interleukin-8; collagen IV sICAM1, sVCAM1 as markers for response to AZD2171 in newly diagnosed glioblastoma patients. (Phase II) VI. Correlation of treatment outcomes with pre-AZD2171 tumor specimens with respect to cell proliferation, apoptosis, microvascular density (MVD), basement membrane and pericyte coverage, angiopoietin-1 and -2 expression to determine whether these immunohistochemical analyses can be predictive of the response to AZD2171. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of cediranib followed by a phase II study.
Patients begin study treatment within 21-42 days after craniotomy or 14-21 days after stereotactic biopsy.
CHEMORADIOTHERAPY: Patients receive cediranib orally (PO) once daily and oral temozolomide once daily for 6 weeks. Within 2-6 hours of dosing, patients undergo concurrent intensity-modulated radiotherapy (IMRT) once daily, 5 days a week for 6 weeks. Cediranib monotherapy: Patients receive cediranib PO once daily for 4 weeks (weeks 7-10). Cediranib and temozolomide monthly therapy: Patients receive cediranib PO once daily for 24 weeks (weeks 11-34) and temozolomide once daily, 5 days a week in weeks 11, 15, 19, 23, 27, and 31. Cediranib monotherapy: Patients receive a fixed-dose of cediranib once daily for 24 weeks (weeks 35-58).
CHEMORADIOTHERAPY: Patients receive cediranib PO at the recommended phase II dose determined in phase Ib, temozolomide PO, and undergo concurrent IMRT as in phase Ib (weeks 1-6). Cediranib monotherapy: Patients receive cediranib PO (at the recommended phase II dose determined in phase Ib) once daily for 4 weeks (weeks 7-10). Cediranib and temozolomide monthly therapy: Patients receive cediranib PO (at the recommended phase II dose determined in phase Ib) once daily for 24 weeks (weeks 11-34) and temozolomide once daily, 5 days a week in weeks 11, 15, 19, 23, 27, and 31. Cediranib monotherapy: Patients receive a fixed-dose of cediranib once daily for 24 weeks (weeks 35-58).
Patients undergo blood and urine sample collection at baseline and periodically during study. Blood samples are measured for tumstatin, as well as other well established biomarkers, including VEGF-A, -D, sVEGFR1, sVEGFR2, sICAM1, sVCAM1, PlGF, PDGF-AA, PDGF-AB, PDGF-BB, thrombospondin-1, and IL-8 by electrochemiluminescence detection. Circulating endothelial cell (CEC) assays are evaluated to assess the kinetics of CECs and progenitor cells prior to and during antiangiogenic therapy with cediranib and chemoradiotherapy. Urine samples are collected for proteomic analyses to evaluate serial change of growth factors such as VEGF and PlGF and of matrix metalloproteinases in response to treatment with cediranib. Archival tumor tissue is collected for analysis of tumor microvascular density, basement membrane and pericyte coverage, angiopoietin-1 and -2 expression, tumor cell proliferation, and apoptosis by immunostaining methods and immunoenzyme techniques.
Patients also undergo dynamic contrast enhanced (DCE)-MRI and T2-weighted or perfusion-weighted MRI at baseline and periodically during study to monitor antiangiogenic effect on tumor vasculature through parameters reflecting both tumor perfusion and permeability; and diffusion tensor imaging to measure degree of water diffusion and fractional anisotropy. A subset of patients undergo fludeoxyglucose F 18 positron emission tomography (FDG-PET) periodically to monitor antiangiogenic effects on glucose utilization.
After completion of study treatment, patients are followed periodically for 1 year.
Trial Contact Information
Trial Lead Organizations/Sponsors
National Cancer Institute
Tracy Batchelor, Principal Investigator
Link to the current ClinicalTrials.gov record.
Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.