High Dose Gefitinib for the Treatment of Carcinomatous Meningitis in Adult Patients With Non-Small Cell Lung Cancer and Known or Suspected EGFR Mutations - Full Text View

Sponsors and Collaborators:	Dana-Farber Cancer Institute AstraZeneca Massachusetts General Hospital
Information provided by:	Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00372515

Purpose

The primary purposes of this study are to find out if using high doses of the drug Gefitinib (Iressa) as a way to treat patients with non-small cell lung cancer that has spread to the covering of the brain and/or spinal cord (meninges) results in any bad side effects; and to determine the highest dose that can be given to patients in this setting.

Condition	Intervention	Phase
Non-Small Cell Lung Cancer	Drug: Gefitinib	Phase I

MedlinePlus related topics: Cancer Lung Cancer Meningitis

Drug Information available for: ZD1839

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety/Efficacy Study
Official Title:	Phase I Study of High Dose Gefitinib (Iressa) for the Treatment of Carcinomatous Meningitis in Adult Patients With Non-Small Cell Lung Cancer and Known or Suspected EGFR Mutations

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:

To assess the safety of administering gefitinib in doses of 750mg to 1250mg in adult patients with carcinomatous meningitis from non-small cell lung cancer with known or suspected somatic EGFR mutations. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To measure the cytologic response rate, response duration, time to neurologic progression, and survival following high dose gefitinib therapy administered on this schedule [ Time Frame: 2 years ] [ Designated as safety issue: No ]
to measure gefitinib levels with serum and cerebrospinal fluid while on therapy, and to correlate these levels with toxicity, response and survival [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
to examine archived tumors for the presence or absence of EGFR mutations and resistance mutations, and to correlate those mutations with cytologic response, time to neurologic progression, and survival. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	18
Study Start Date:	June 2006
Estimated Study Completion Date:	July 2009
Estimated Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Intervention Details:

On days 1-14 gefitinib will be taken orally daily at either 750, 1000, or 1250mg (depends upon when subject entered trial). If medication is tolerated well, subject will take 500mg daily on days 15-28 of each 28-day cycle. Cycles (higher dose followed by lower dose) will be repeated as long as subject's cancer does not worsen and they do not experience any serious side effects.

Detailed Description:

The standard therapy for this type of cancer is to give chemotherapy directly into the spinal fluid, usually by a spinal tap. Some chemotherapy may, in some cases, be combined with radiation. This study looks at a different way of treating this type of cancer.
This study is specifically for patients whose lung cancer has changes in a protein called the epidermal growth factor receptor (EGFR). The study drug, gefitinib, was developed to stop the signals from the EGFR that tell certain types of lung cancers tumors to grow. By using higher doses than are normally used, we hope to increase the amount of drug in the spinal fluid to attempt to kill the cancer cells around the spinal cord and brain.
Since we are looking for the highest dose of gefitinib that can be given safely, not everyone who participates in this study will be receiving the same amount of drug.
Patients will start taking gefitinib daily by mouth on Day 1 and will continue taking this medication daily at home. On the first day the patient takes gefitinib and on Day 14 of each treatment cycle (1 cycle equals 28 days), the patient will undergo: Physical examination by the study doctor and a detailed neurological exam by a neuro-oncologist; sampling of cerebrospinal fluid (CSF) by lumbar puncture; review of current medications; measurement of vital signs; check on the patients ability to perform daily activities; blood work.
If the patient is tolerating the study medication well, then the patient will receive a lower dose for days 15-28 of the cycle.
At the end of each cycle on Day 28, the patient will meet with the study doctor and have the following: a physical examination; review of current medications; measurement of vital signs, check on the patients ability to perform daily activities; blood tests; MRI of the brain and spinal cord to assess tumor response; every two cycles a CT scan of the chest and abdomen to assess the tumor response.

Eligibility

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

Criteria

Inclusion Criteria:

Histologically or cytologically proven diagnosis of non-small cell lung cancer of any histologic subtype
High likelihood of gefitinib sensitivity, as evidenced by one or more of the following: previous complete or partial response to treatment with an epidermal growth factor receptor-tyrosine kinase inhibitor, erlotinib, or gefitinib; known somatic mutation of the EGFR tyrosine kinase
Recurrent or persistent disease as manifested by carcinomatous meningitis
ECOG PS 0-3
Age 18 years or older
Greater than 2 weeks since prior radiation therapy
Greater than 3 weeks since prior major surgery
Adequate hematologic, renal, and/or hepatic function
Coagulation parameters: international normalized ratio(INR)less than or equal to 1.5 and an activated thromboplastin time < 50 seconds

Exclusion Criteria:

Previous Grade 4 toxicity on gefitinib or erlotinib leading to dose reduction or interruption
Uncontrolled brain metastases, or brain metastases associated with mass effect that would contraindicate lumbar puncture
Any other malignancy within the past five years, except for adequately treated carcinoma of the cervix, basal or squamous cell carcinomas of the skin
Dysphagia
Active gastrointestinal disease or disorder that alters gastrointestinal motility or absorption
Incomplete healing from previous oncologic or other major surgery
Any pre-existing severe or unstable medical condition
Any condition requiring concurrent and ongoing use of anticoagulation
Inability to undergo collection of CSF, either by repeated lumbar puncture or placement of an Omaya reservoir
Pregnant or breastfeeding
Concurrent intrathecal drug administration or radiotherapy
Concurrent systemic chemotherapy or investigational agent
Anticoagulant except aspirin or heparin flushes
Enzyme-inducing anti-epileptic drug
CYP3A4 inhibitors

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00372515

Locations

United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Dana-Farber Cancer Institute

AstraZeneca

Massachusetts General Hospital

Investigators

Principal Investigator:

Bruce Johnson, MD

Dana-Farber Cancer Institute

More Information

No publications provided

Responsible Party:	Dana-Farber Cancer Institute ( David Jackman, MDq )
Study ID Numbers:	05-403
Study First Received:	September 6, 2006
Last Updated:	April 24, 2009
ClinicalTrials.gov Identifier:	NCT00372515 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:

epidermal growth factor
EGFR
lung cancer
Iressa
Gefitinib

Study placed in the following topic categories:

Thoracic Neoplasms
Meningeal Neoplasms
Central Nervous System Diseases
Central Nervous System Neoplasms
Protein Kinase Inhibitors
Meningitis
Carcinoma
Respiratory Tract Diseases
Central Nervous System Infections

Lung Neoplasms
Lung Diseases
Mitogens
Non-small Cell Lung Cancer
Gefitinib
Carcinoma, Non-Small-Cell Lung
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Thoracic Neoplasms
Meningeal Neoplasms
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Central Nervous System Neoplasms
Protein Kinase Inhibitors
Meningitis
Neoplasms by Site
Respiratory Tract Diseases
Lung Neoplasms
Therapeutic Uses
Gefitinib
Nervous System Neoplasms

Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Nervous System Diseases
Central Nervous System Diseases
Enzyme Inhibitors
Pharmacologic Actions
Carcinoma
Neoplasms
Central Nervous System Infections
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 06, 2009