Clinical trial NCT00025207: Gefitinib in Treating Patients With Malignant Mesothelioma
Official title: A Phase II Study Of ZD 1839 (NSC 715055, IND 61187) In Patients With Malignant Mesothelioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Malignant Mesothelioma
Epithelial Mesothelioma
Recurrent Malignant Mesothelioma
Sarcomatous Mesothelioma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-09-10
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

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 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

Primary outcomes:
measure: Percentage of patients who remain failure-free
timeFrame: Time between the initiation of treatment and initial failure (disease progression, relapse, death), assessed up to 3 months
Secondary outcomes:
measure: Tumor response rate
timeFrame: Up to 4 years
measure: Toxicities, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0
timeFrame: Up to 4 years
measure: Overall survival
timeFrame: Up to 4 years
measure: Failure-free survival within patient subgroups defined in terms of epidermal growth factor receptor (EGFR) overexpression and cyclooxygenase-2 (COX-2) expression
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Cancer and Leukemia Group B
state: Illinois
Study officials:
affiliation: Cancer and Leukemia Group B
name: Ramaswamy Govindan
role: PRINCIPAL_INVESTIGATOR
References: