S0509 - AZD2171 in Treating Patients With Malignant Pleural 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:
NCT00243074
First received: October 20, 2005
Last updated: September 21, 2015
Last verified: February 2014
  Purpose
This phase II trial is study how well AZD2171 works in treating patients with malignant pleural mesothelioma that cannot be removed by surgery. 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

Condition Intervention Phase
Advanced Malignant Mesothelioma
Epithelial Mesothelioma
Recurrent Malignant Mesothelioma
Sarcomatous Mesothelioma
Drug: cediranib maleate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
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 National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall Response Rate [ Time Frame: Disease assessments for response were performed every 8 weeks for as long as the patient remained on protocol treatment, up to 5 years. ] [ Designated as safety issue: No ]
    confirmed complete and partial responses per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.".


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: Daily during protocol treatment; then every 8 weeks until progression; then every 6 months for up to 3 years. ] [ Designated as safety issue: No ]
    From the date of enrollment until the date of death due to any cause. Patients last known to be alive were censored at the date of last contact.

  • Progression-free Survival [ Time Frame: Every 8 weeks until disease progression or death, up to 5 years. ] [ Designated as safety issue: No ]
    From the date of enrollment until the date of disease progression (as determined by standard RECIST), symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free were censored at the date of last contact. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

  • Disease Control Rate [ Time Frame: Every 8 weeks until disease progression progression, up to 5 years. ] [ Designated as safety issue: No ]
    The percentage of patients with a best of response of stable disease or better per standard RECIST. That is, patients whose best response was not increasing disease or death.

  • Objective Response Rate Per Modified RECIST for Pleural Tumors [ Time Frame: Disease assessments for response were performed every 8 weeks as long as the patient remained on protocol treatment, up to 5 years. ] [ Designated as safety issue: No ]
    The sum of 6 pleural thickness measurements is added to sum of the longest diameters of all non-pleural measurable lesions. The resulting values are evaluated using RECIST.

  • Adverse Event Rates [ Time Frame: Daily during protocol treatment ] [ Designated as safety issue: Yes ]
    Adverse events per the NCI Common Toxicity Criteria version 3.0 that were possibly, probably or definitely related to protocol treatment.

  • Adverse Events [ Time Frame: Patients were assessed for adverse events every day for as long as they remained on protocol treatment, up to 5 years. ] [ Designated as safety issue: Yes ]
    Only adverse events that are possibly, probably or definitely related to study drug are reported.


Enrollment: 54
Study Start Date: November 2005
Study Completion Date: December 2011
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cediranib maleate)
Patients receive oral AZD2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: cediranib maleate
Given orally
Other Names:
  • AZD2171
  • Recentin
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

I. Determine the clinical benefit, in terms of objective response and stable disease rates, in patients treated with this drug.

II. Determine the 1-year median overall survival and progression-free survival in patients treated with this drug.

III. Determine the frequency and severity of toxic effects in patients treated with this drug.

IV. 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.

V. Correlate, preliminarily, circulating endothelial cells with clinical outcomes in patients treated with this drug.

VI. 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:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Performance status

    • Zubrod 0-2
  • WBC >= 3,000/mm^3
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • AST or ALT =< 1.5 times upper limit of normal (ULN)
  • Bilirubin normal
  • Creatinine =< 1.5 times ULN OR
  • Creatinine clearance >= 50 mL/min
  • Proteinuria =< 1+ by 2 consecutive dipstick tests taken >= 1 week apart
  • 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
  • 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
  • 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 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 proarrhythmic potential
  • No more than 1 prior chemotherapy regimen
  • At least 28 days since prior chemotherapy (42 days for nitrosoureas or mitomycin) and recovered
  • At least 21 days since prior radiotherapy and recovered
  • At least 28 days since prior major surgery (e.g., thoracotomy or laparotomy) and recovered
  • No prior surgery that would affect absorption
  • 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

Locations
United States, Texas
Southwest Oncology Group
San Antonio, Texas, United States, 78245
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Linda Garland Southwest Oncology Group
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00243074     History of Changes
Other Study ID Numbers: NCI-2012-02902  S0509  U10CA032102  CDR0000446178 
Study First Received: October 20, 2005
Results First Received: October 30, 2012
Last Updated: September 21, 2015
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 21, 2016