Gefitinib in Treating Patients With Malignant Mesothelioma

A Phase II Study Of ZD 1839 (NSC 715055, IND 61187) In Patients With Malignant Mesothelioma

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

Study Overview

• Status: Completed
• Conditions: Recurrent Malignant Mesothelioma; Advanced Malignant Mesothelioma; Epithelial Mesothelioma; Sarcomatous Mesothelioma
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: gefitinib

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60606
      • Cancer and Leukemia Group B

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Other: laboratory biomarker analysis; Correlative studies; Drug: gefitinib; Given orally; Other Names: Iressa; ZD 1839

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients who remain failure-free	Kaplan-Meier's product limit estimator and curves will be used.	Time between the initiation of treatment and initial failure (disease progression, relapse, death), assessed up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor response rate	An exact binomial confidence interval will be generated.	Up to 4 years
Toxicities, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0	For each type of toxicity experienced, the frequency of reported toxicity will be summarized by the most severe grade.	Up to 4 years
Overall survival	Kaplan-Meier's product limit estimator and curves will be used.	Up to 4 years
Failure-free survival within patient subgroups defined in terms of epidermal growth factor receptor (EGFR) overexpression and cyclooxygenase-2 (COX-2) expression	An exact binomial confidence interval will be generated.	Up to 4 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ramaswamy Govindan, Cancer and Leukemia Group B

Study record dates

Study Major Dates

• Study Start: September 1, 2001
• Primary Completion (Actual): February 1, 2006

Study Registration Dates

• First Submitted: October 11, 2001
• First Submitted That Met QC Criteria: September 9, 2003
• First Posted (Estimate): September 10, 2003

Study Record Updates

• Last Update Posted (Estimate): January 17, 2013
• Last Update Submitted That Met QC Criteria: January 15, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Gefitinib
• Other Study ID Numbers: NCI-2012-02414; U10CA031946 (U.S. NIH Grant/Contract); CLB-30101; CDR0000068938 (Registry Identifier: PDQ (Physician Data Query))