Cediranib Maleate in Treating Patients With Malignant Mesothelioma That Cannot Be Removed By Surgery

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00309946
First received: March 29, 2006
Last updated: July 25, 2014
Last verified: October 2013
  Purpose

This phase II trial is studying how well cediranib maleate works in treating patients with malignant mesothelioma that cannot be removed by surgery. Cediranib maleate 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


Condition Intervention Phase
Advanced Malignant Mesothelioma
Epithelial Mesothelioma
Localized Malignant Mesothelioma
Recurrent Malignant Mesothelioma
Sarcomatous Mesothelioma
Drug: cediranib maleate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of AZD2171 (NSC#732208) in Patients With Malignant Mesothelioma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Objective Response Rate, Complete (CR) or Partial (PR) Response [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
    Evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. To be assigned a status of PR or CR, changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response are first met.


Secondary Outcome Measures:
  • Changes in Laboratory Correlates [ Time Frame: Baseline, days 15 and 29 of course 1, and then every 28 days ] [ Designated as safety issue: No ]
    Examined using paired t-test or Wilcoxon signed-ranks test.

  • Pharmacogenomics by Correlating Genetic Polymorphisms With Drug Activity and Toxicity [ Time Frame: Week 1 of course 1 ] [ Designated as safety issue: Yes ]
    Focus on variants of genes in the pathway targeted by cediranib maleate, including kdr/flk-1 (the specific target of cediranib maleate) and the genes that encode Vascular endothelial growth factor A (VEGF-A) or HIF1α. If additional information relevant to other genes of interest in the pathway becomes available the samples will be utilized for such analysis as well.


Enrollment: 51
Study Start Date: December 2005
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (enzyme inhibitor therapy)
Initial cediranib maleate dosing was 45 mg (once daily) during a 28-day cycle. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. Due to substantial toxicity, the starting dose was subsequently lowered to 30 mg daily.
Drug: cediranib maleate
Given orally
Other Names:
  • AZD2171
  • Recentin

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed malignant pleural, peritoneal, or tunica vaginalis mesothelioma

    • Epithelial, sarcomatoid, or mixed subtype
  • International Mesothelioma Interest Group stage II-IV disease (for patients with pleural mesothelioma)
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR > 10 mm by spiral CT scan

    • Pleural effusion and ascites are not considered measurable lesions
  • Disease not amenable to curative surgery
  • No known brain metastases
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 OR Karnofsky PS 70-100%
  • Life expectancy > 3 months
  • White blood cell (WBC) ≥ 3,000/mm³
  • Absolute neutrophil count ≥ 1,500/mm³
  • Hemoglobin ≥ 8 g/dL
  • Platelets ≥ 100,000/mm³
  • Total bilirubin normal
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 times upper limit of normal(ULN)
  • Creatinine normal OR creatinine clearance > 60 mL/min
  • Fertile patients must use effective contraception
  • Not pregnant or nursing
  • Negative pregnancy test
  • No history of allergic reactions to compounds of similar chemical or biologic composition to AZD2171
  • Mean corrected QT interval (QTc) ≤ 500 msec (with Bazett's correction) by EKG
  • No history of long QT syndrome
  • Proteinuria ≤ 1+ on two consecutive dipsticks taken ≥ 1 week apart
  • No other concurrent malignancy
  • No New York Heart Association class III or IV cardiac disease
  • No uncontrolled intercurrent illness including, but not limited to, any of the following:

    • Hypertension
    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness or social situations that would limit study compliance
  • No more than 1 prior cytotoxic chemotherapy

    • Prior intrapleural cytotoxic agents (including bleomycin) do not count towards prior cytotoxic chemotherapy
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
  • No prior radiotherapy to the only site of measurable disease
  • At least 4 weeks since prior radiotherapy and recovered
  • At least 4 weeks since prior major surgery and recovered
  • More than 30 days since prior participation in an investigational trial
  • No prior treatment with a vascular endothelial growth factor (VEGF) inhibitor
  • No other concurrent investigational agents
  • No concurrent commercial agents for the malignancy
  • No concurrent medication that may markedly affect renal function (e.g., vancomycin, amphotericin, or pentamidine)
  • No concurrent hematopoietic growth factors except epoetin alfa
  • No concurrent palliative radiotherapy
  • No combination antiretroviral therapy for HIV-positive patients
  • No concurrent drugs or biologics with proarrhythmic potential
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00309946

Locations
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
Sponsors and Collaborators
Investigators
Principal Investigator: Hedy Kindler University of Chicago Comprehensive Cancer Center
  More Information

Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00309946     History of Changes
Other Study ID Numbers: NCI-2009-00126, N01CM17102, CDR0000463521, 14203B
Study First Received: March 29, 2006
Results First Received: July 1, 2013
Last Updated: July 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Mesothelioma
Neoplasms, Mesothelial
Lung Neoplasms
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Cediranib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014