Gefitinib in Treating Patients With Malignant Mesothelioma

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Epithelial Mesothelioma

Advanced Malignant Mesothelioma

Recurrent Malignant Mesothelioma

Sarcomatous Mesothelioma

Treatments

Drug: gefitinib

Other: laboratory biomarker analysis

Study type

Interventional

Funder types

NIH

Identifiers

NCT00025207

CLB-30101

CDR0000068938 (Registry Identifier)

U10CA031946 (U.S. NIH Grant/Contract)

NCI-2012-02414

Details and patient eligibility

About

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

Full 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.

Enrollment

40 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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