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| Sponsor: | M.D. Anderson Cancer Center |
|---|---|
| Collaborator: |
National Cancer Institute (NCI) |
| Information provided by (Responsible Party): | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT00458731 |
Purpose
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. AZD2171 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Bevacizumab and AZD2171 may also stop the growth of cancer cells by blocking blood flow to the cancer. Giving bevacizumab together with AZD2171 may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of bevacizumab and AZD2171 in treating patients with metastatic or unresectable solid tumor, lymphoma, intracranial glioblastoma, gliosarcoma or anaplastic astrocytoma.
| Condition | Intervention | Phase |
|---|---|---|
|
Brain and Central Nervous System Tumors Lymphoma Intestinal Neoplasms Unspecified Adult Solid Tumor, Protocol Specific |
Biological: Bevacizumab (Avastin™) Drug: AZD2171 (Cediranib Maleate) |
Phase I |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase I Clinical Trial Evaluating the Toxicity, Pharmacokinetics and Biological Effect of Intravenous Bevacizumab (Avastin™) in Combination With Escalating Doses of Oral AZD2171 for Patients With Advanced Malignancies |
| Estimated Enrollment: | 66 |
| Study Start Date: | May 2007 |
| Estimated Primary Completion Date: | May 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Bevacizumab + AZD2171 |
Biological: Bevacizumab (Avastin™)
Starting dose 3 mg/kg IV every two weeks (days 1 and 15)
Other Names:
Drug: AZD2171 (Cediranib Maleate)
Starting dose 20 mg oral daily for 21 consecutive days (days 1-21)
Other Name: Cediranib
|
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a dose-escalation study.
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral AZD2171 once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of bevacizumab and AZD2171 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Blood samples are acquired at baseline, on day 2, and after 2 courses of treatment for pharmacokinetic studies. Samples are analyzed by TUNEL, immunofluorescence staining, laser-scanning cytometry, flow cytometry, enzyme-linked immunosorbent assay, and immunohistochemistry to assess apoptosis in tumor and endothelial cells, microvessel density mean vessel volume, nitric oxide concentration, and signal transduction pathways (i.e., ERK ½, P38 mitogen-activated protein kinase, protein kinase B, circulating endothelial and progenitor cells, basic fibroblast growth factor, vascular endothelial growth factor (VEGF) receptor phosphorylation, VEGF, and hypoxia inducible factor-1α). Some patients also undergo tissue biopsy at baseline and after 2 courses of treatment for characterization of vascular and angiogenesis markers. Some patients also undergo DCE-MRI at baseline, once between days 22-24, and after every 2 courses of treatment to assess blood perfusion.
After completion of study treatment, patients are followed for 6 weeks.
PROJECTED ACCRUAL: A total of 66 patients will be accrued for this study.
Eligibility| Ages Eligible for Study: | 15 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contacts and Locations| United States, Texas | |
| M. D. Anderson Cancer Center at University of Texas | |
| Houston, Texas, United States, 77030-4009 | |
| Study Chair: | David Hong, MD | M.D. Anderson Cancer Center |
More Information
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT00458731 History of Changes |
| Other Study ID Numbers: | 2005-0910, U01CA062461, P30CA016672, MDA-MDACC-2005-0910, CDR0000538277 |
| Study First Received: | April 9, 2007 |
| Last Updated: | December 15, 2011 |
| Health Authority: | United States: Food and Drug Administration |
|
Advanced Cancer Intravenous Bevacizumab Avastin Oral AZD2171 Cediranib Maleate small intestine cancer unspecified adult solid tumor, protocol specific AIDS-related peripheral/systemic lymphoma AIDS-related primary CNS lymphoma anaplastic large cell lymphoma angioimmunoblastic T-cell lymphoma extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue intraocular lymphoma nodal marginal zone B-cell lymphoma primary central nervous system non-Hodgkin lymphoma |
primary central nervous system Hodgkin lymphoma recurrent adult Burkitt lymphoma recurrent adult diffuse large cell lymphoma recurrent adult diffuse mixed cell lymphoma recurrent adult diffuse small cleaved cell lymphoma recurrent adult Hodgkin lymphoma recurrent adult immunoblastic large cell lymphoma recurrent adult lymphoblastic lymphoma recurrent adult T-cell leukemia/lymphoma recurrent cutaneous T-cell non-Hodgkin lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma recurrent mantle cell lymphoma recurrent marginal zone lymphoma |
|
Astrocytoma Neoplasms Glioblastoma Intestinal Neoplasms Lymphoma Lymphoma, Non-Hodgkin Nervous System Neoplasms Lymphoma, Large-Cell, Immunoblastic Central Nervous System Neoplasms Lymphoma, Large-Cell, Anaplastic Gliosarcoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal |
Neoplasms by Histologic Type Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases Intestinal Diseases Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Nervous System Diseases Lymphoma, T-Cell |