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Bevacizumab and AZD2171 in Treating Patients With Metastatic or Unresectable Solid Tumor or Lymphoma

This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), June 2007

Sponsors and Collaborators: M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
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 or lymphoma.


Condition Intervention Phase
Lymphoma
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: bevacizumab
Drug: cediranib
Procedure: TdT-mediated dUTP nick end labeling assay
Procedure: biopsy
Procedure: dynamic contrast-enhanced magnetic resonance imaging
Procedure: flow cytometry
Procedure: fluorescent antibody technique
Procedure: immunohistochemistry staining method
Procedure: laboratory biomarker analysis
Procedure: pharmacological study
Phase I

MedlinePlus related topics:   Cancer    Fungal Infections    Hodgkin's Disease    Intestinal Cancer    Leukemia, Adult Acute    Leukemia, Adult Chronic    Lymphoma   

ChemIDplus related topics:   Bevacizumab    Cediranib   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose [ Designated as safety issue: Yes ]
  • Pharmacokinetics of bevacizumab and AZD2171 [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Vascular endothelial growth factor expression in malignant effusions [ Designated as safety issue: No ]
  • Response rate [ Designated as safety issue: No ]
  • Association between nitric oxide and blood pressure [ Designated as safety issue: No ]

Estimated Enrollment:   51
Study Start Date:   May 2007
Estimated Primary Completion Date:   October 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

  • Determine the safety and toxicity of bevacizumab and AZD2171 in patients with metastatic or unresectable solid tumor or lymphoma.
  • Determine the pharmacokinetic profile of this regimen in these patients.

Secondary

  • Correlate serum concentrations of nitric oxide (NO) and NO synthase with vascular endothelial growth factor (VEGF) expression in patients treated with this regimen.
  • Evaluate changes in tumor vasculature detected by dynamic contrast-enhanced MRI in patients treated with this regimen.
  • Determine the potential predictive role of angiogenesis molecular endpoints (e.g., VEGF) in malignant effusion samples.
  • Determine, preliminarily, the efficacy of this regimen in these patients.

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). 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 51 patients will be accrued for this study.

  Eligibility
Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed metastatic or unresectable solid tumor or lymphoma

    • If assessing a single target lesion, histological confirmation of that particular lesion is required
  • Stable brain metastasis allowed provided the following criteria are met:

    • Stable disease on MRI ≥ 4 weeks after completion of whole brain radiation
    • No evidence of progression on MRI 4 weeks after completion of stereotactic radiosurgery
    • Brain metastasis was completely excised
  • No squamous cell non-small cell lung carcinoma

PATIENT CHARACTERISTICS:

  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • WBC ≥ 3,000/mm³
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Bilirubin ≤ 2.0 mg/dL (unless Gilbert's syndrome is present)
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5.0 times ULN if due to liver involvement)
  • Serum creatinine ≤ 2.0 mg/dL
  • Proteinuria < 1+ by dipstick or urine analysis
  • Urine protein:creatinine ratio < 1.0 OR urine protein < 1,000 mg by 24-hour urine collection
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • No significant traumatic injury within the past 28 days
  • No QTc prolongation (i.e., QTc > 500 msec) or other significant ECG abnormality within the past 14 days
  • No serious or non-healing wound, ulcer, or bone fracture
  • No bleeding diathesis, defined as PT and aPTT ≥ 1.5 times ULN or INR ≥ 1.5
  • No active gastric or duodenal ulcer
  • No uncontrolled systemic vascular hypertension, defined as systolic blood pressure (BP) > 140 mm Hg and diastolic BP > 90 mm Hg
  • No concurrent uncontrolled illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics
  • No conditions requiring drugs or biologics with proarrhythmic potential
  • No clinically significant cardiovascular disease, including the following:

    • Cerebrovascular accident within the past 6 months
    • Myocardial infarction or unstable angina within the past 6 months
    • New York Heart Association class II-IV congestive heart failure
    • Serious cardiac arrhythmia requiring medication
    • Unstable angina pectoris
    • Clinically significant peripheral vascular disease
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • Recovered from all prior therapy
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • More than 28 days since prior major surgeries or open biopsy
  • More than 7 days since prior core biopsy
  • No concurrent major surgery
  • No other concurrent investigational agents
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00458731

Locations
United States, Texas
M. D. Anderson Cancer Center at University of Texas     Recruiting
      Houston, Texas, United States, 77030-4009
      Contact: Clinical Trials Office - M. D. Anderson Cancer Center at the U     713-792-3245        

Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)

Investigators
Study Chair:     Luis H. Camacho, MD, MPH     M.D. Anderson Cancer Center    
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site
 

Study ID Numbers:   CDR0000538277, MDA-MDACC-2005-0910
First Received:   April 9, 2007
Last Updated:   July 23, 2008
ClinicalTrials.gov Identifier:   NCT00458731
Health Authority:   Unspecified

Keywords provided by National Cancer Institute (NCI):
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 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
recurrent mycosis fungoides/Sezary syndrome
recurrent small lymphocytic lymphoma
small intestine lymphoma
splenic marginal zone lymphoma
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma

Study placed in the following topic categories:
Sezary syndrome
Lymphoma, Mantle-Cell
Hodgkin lymphoma, adult
Lymphoma, small cleaved-cell, diffuse
Bevacizumab
Lymphoma, large-cell, immunoblastic
Central nervous system lymphoma, primary
Duodenal Neoplasms
Mycoses
Lymphoma, Large-Cell, Anaplastic
Hodgkin Disease
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Digestive System Neoplasms
Leukemia, B-cell, chronic
Waldenstrom Macroglobulinemia
B-cell lymphomas
Leukemia, T-Cell
Gastrointestinal Neoplasms
Anaplastic large cell lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell, Cutaneous
Hodgkin's disease
Gastrointestinal Diseases
Cutaneous T-cell lymphoma
Lymphoma, Follicular
Lymphoma, B-Cell, Marginal Zone
Sezary Syndrome
Mycosis Fungoides
Lymphoma, B-Cell

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Immune System Diseases
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Ileal Diseases
Angiogenesis Inhibitors
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Jejunal Diseases
Therapeutic Uses
Angiogenesis Modulating Agents
Growth Inhibitors

ClinicalTrials.gov processed this record on August 27, 2008




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