S0509: AZD2171 in Treating Patients With Malignant Pleural Mesothelioma That Cannot Be Removed By Surgery

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00243074
First received: October 20, 2005
Last updated: October 30, 2012
Last verified: October 2012
  Purpose

RATIONALE: AZD2171 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.

PURPOSE: This phase II trial is study how well AZD2171 works in treating patients with malignant pleural mesothelioma that cannot be removed by surgery.


Condition Intervention Phase
Malignant Mesothelioma
Drug: cediranib maleate
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Novel Oral Anti-Angiogenic Agent AZD2171 (NSC-732208) in Malignant Pleural Mesothelioma

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Overall response rate (complete response and partial response) [ Time Frame: 3 years or until death ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: 3 years or until death ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: 3 years or until death ] [ Designated as safety issue: No ]
  • Time to treatment failure [ Time Frame: Every 8 weeks until progression ] [ Designated as safety issue: No ]
  • Relationship between molecular/genetic correlates of the angiogenesis pathway with survival and response [ Time Frame: At week 1, week 8 and week 16 ] [ Designated as safety issue: No ]

Enrollment: 53
Study Start Date: November 2005
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AZD2171 Drug: cediranib maleate
45 mg/day by mouth, Days 1 - 28, Daily. There will be no pause between cycles.

Detailed Description:

OBJECTIVES:

Primary

  • Determine the objective confirmed, complete, and partial response rates in patients with unresectable malignant pleural mesothelioma treated with AZD2171.

Secondary

  • Determine the clinical benefit, in terms of objective response and stable disease rates, in patients treated with this drug.
  • Determine the 1-year median overall survival and progression-free survival in patients treated with this drug.
  • Determine the frequency and severity of toxic effects in patients treated with this drug.
  • Correlate, preliminarily, pre- and post-treatment plasma vascular endothelial growth factor and soluble vascular cell adhesion molecule with clinical outcomes in patients treated with this drug.
  • Correlate, preliminarily, circulating endothelial cells with clinical outcomes in patients treated with this drug.
  • Correlate variants of genes in the pathway targeted by this drug and variants of genes involved in the development of hypertension with the antiangiogenic property of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral AZD2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 5 years from study entry.

PROJECTED ACCRUAL: A total of 40 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 epithelial, sarcomatous, or biphasic malignant pleural mesothelioma

    • Unresectable disease

      • Residual disease after prior cytoreductive surgery allowed
  • Measurable disease by CT scan or MRI
  • Prior treatment with platinum-based chemotherapy required
  • No known CNS metastasis

PATIENT CHARACTERISTICS:

Performance status

  • Zubrod 0-2

Life expectancy

  • Not specified

Hematopoietic

  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • AST or ALT ≤ 1.5 times upper limit of normal (ULN)
  • Bilirubin normal

Renal

  • Creatinine ≤ 1.5 times ULN OR
  • Creatinine clearance ≥ 50 mL/min
  • Proteinuria ≤ 1+ by 2 consecutive dipstick tests taken ≥ 1 week apart

Cardiovascular

  • No history of familial long QT syndrome
  • Mean QTc ≤ 470 msec
  • Systolic BP ≤ 150 mm Hg AND diastolic BP ≤ 100 mm Hg
  • Must have New York Heart Association class I or II disease

    • Class II must be controlled with treatment

Gastrointestinal

  • Able to swallow and/or receive enteral medications via gastrostomy feeding tube
  • Not requiring IV alimentation
  • No active peptic ulcer
  • No intractable nausea or vomiting

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in remission
  • No history of hypersensitivity reaction to compounds of similar chemical or biological composition to the study drug

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Prior monoclonal antibody therapy targeting vascular endothelial growth factor (VEGF), VEGF receptor 1 (VEGFR1) or VEGF receptor 2 (VEGFR2) allowed
  • No other prior immunotherapy or biologic therapy
  • No prior thymidine kinase inhibitor against VEGFR1 or VEGFR2
  • No concurrent drugs or biologics with proarrythmic potential

Chemotherapy

  • See Disease Characteristics
  • No more than 1 prior chemotherapy regimen
  • At least 28 days since prior chemotherapy (42 days for nitrosoureas or mitomycin) and recovered

Radiotherapy

  • At least 21 days since prior radiotherapy and recovered

Surgery

  • See Disease Characteristics
  • At least 28 days since prior major surgery (e.g., thoracotomy or laparotomy) and recovered
  • No prior surgery that would affect absorption

Other

  • Stable antihypertensive therapy allowed provided blood pressure (BP) parameters are met
  • Concurrent enrollment on SWOG-S9925 allowed
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  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: NCT00243074

  Show 90 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Study Chair: Linda Garland, MD University of Arizona
Study Chair: Antoinette J. Wozniak, MD Barbara Ann Karmanos Cancer Institute
  More Information

Additional Information:
Publications:
Garland LL, Chansky K, Wozniak A, et al.: SWOG S0509: A phase II study of novel oral antiangiogenic agent AZD2171 (NSC-732208) in malignant pleural mesothelioma. [Abstract] J Clin Oncol 27 (Suppl 15): A-7511, 2009.

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00243074     History of Changes
Other Study ID Numbers: CDR0000446178, U10CA032102, S0509
Study First Received: October 20, 2005
Last Updated: October 30, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:
epithelial mesothelioma
sarcomatous mesothelioma
advanced malignant mesothelioma
recurrent malignant mesothelioma

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
Maleic acid
Cediranib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 19, 2014