Gefitinib in Treating Patients With Malignant Mesothelioma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00025207
First received: October 11, 2001
Last updated: January 15, 2013
Last verified: January 2013
  Purpose

Phase II trial to study the effectiveness of gefitinib in treating patients who have malignant mesothelioma. Biological therapies such as gefitinib may interfere with the growth of the tumor cells and slow the growth of malignant mesothelioma


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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study Of ZD 1839 (NSC 715055, IND 61187) In Patients With Malignant Mesothelioma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Percentage of patients who remain failure-free [ Time Frame: Time between the initiation of treatment and initial failure (disease progression, relapse, death), assessed up to 3 months ] [ Designated as safety issue: No ]
    Kaplan-Meier's product limit estimator and curves will be used.


Secondary Outcome Measures:
  • Tumor response rate [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    An exact binomial confidence interval will be generated.

  • Toxicities, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]
    For each type of toxicity experienced, the frequency of reported toxicity will be summarized by the most severe grade.

  • Overall survival [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Kaplan-Meier's product limit estimator and curves will be used.

  • Failure-free survival within patient subgroups defined in terms of epidermal growth factor receptor (EGFR) overexpression and cyclooxygenase-2 (COX-2) expression [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    An exact binomial confidence interval will be generated.


Enrollment: 40
Study Start Date: September 2001
Primary Completion Date: February 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (gefitinib)
Patients receive oral gefitinib once daily on days 1-21. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Drug: gefitinib
Given orally
Other Names:
  • Iressa
  • ZD 1839
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

OBJECTIVES:

I. Determine the activity of gefitinib, in terms of failure-free survival, in patients with malignant mesothelioma.

II. Determine the response rate in patients treated with this drug. III. Determine the toxicity of this drug in these patients. IV. Determine the overall survival of patients treated with this drug. V. Determine whether overexpression of epidermal growth factor receptor and expression of cyclo-oxygenase-2 can predict the effectiveness of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral gefitinib once daily on days 1-21. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year and then every 6 months for up to 3 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 7-10 months.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed malignant mesothelioma that is not amenable to curative surgery or radiotherapy

    • Epithelial, sarcomatoid, or mixed subtype
    • Any site of origin (including, but not limited to, the pleura, peritoneum, pericardium, or tunica vaginalis) allowed
  • Measurable disease, defined as lesions that can be accurately measured in at least 1 dimension (longest diameter) as at least 20 mm with conventional techniques or at least 10 mm with spiral CT scan

    • Must be outside prior radiation port
    • Lesions not considered measurable include the following:

      • Bone lesions
      • Leptomeningeal disease
      • Ascites
      • Pleural/pericardial effusion
      • Inflammatory breast disease
      • Lymphangitis cutis/pulmonis
      • Abdominal masses not confirmed and followed by imaging techniques
      • Cystic lesions
  • No known brain metastases
  • Performance status - CTC 0-1
  • Granulocyte count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • SGOT no greater than 2.5 times ULN
  • Creatinine no greater than 1.5 times ULN
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No other concurrent active malignancy except nonmelanoma skin cancer

    • Disease considered not currently active if completely treated with less than a 30% risk for relapse
  • No other concurrent uncontrolled illness
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study compliance
  • No prior epidermal growth factor receptor-inhibitor therapy
  • Prior intrapleural cytotoxic or sclerosing agents (including bleomycin) allowed
  • No prior systemic cytotoxic chemotherapy for malignant mesothelioma
  • No concurrent chemotherapy
  • At least 1 week since prior CYP3A4 inducers (e.g., dexamethasone, glucocorticoids, progesterone)
  • No concurrent CYP3A4 inducers (e.g., dexamethasone)
  • No concurrent hormonal therapy (e.g., tamoxifen) except steroids for adrenal failure or hormones for non disease-related conditions (e.g., insulin for diabetes)
  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy
  • No concurrent radiotherapy, including for palliation
  • See Disease Characteristics
  • At least 2 weeks since prior major surgery
  • At least 1 week since other prior CYP3A4 inducers (e.g., carbamazepine, ethosuximide, griseofulvin, nafcillin, nelfinavir mesylate, nevirapine, oxcarbazepine, phenobarbital, phenylbutazone, phenytoin, primidone, rifabutin, rifampin, rofecoxib, St. John's Wort, sulfadimidine, sulfinpyrazone, or troglitazone)
  • No other concurrent CYP3A4 inducers
  • No concurrent CYP3A4 substrates or inhibitors
  • No other concurrent investigational agent
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent chlorpromazine, amiodarone, or chloroquine
  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: NCT00025207

Locations
United States, Illinois
Cancer and Leukemia Group B
Chicago, Illinois, United States, 60606
Sponsors and Collaborators
Investigators
Principal Investigator: Ramaswamy Govindan Cancer and Leukemia Group B
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00025207     History of Changes
Other Study ID Numbers: NCI-2012-02414, CLB-30101, U10CA031946, CDR0000068938
Study First Received: October 11, 2001
Last Updated: January 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Gefitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014