search
Back to results

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

Primary Purpose

Non-Small Cell Lung Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Gefitinib
Sponsored by
David M. Jackman, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring epidermal growth factor, EGFR, lung cancer, Iressa, Gefitinib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General Hospital
  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

High dose gefitinib

Arm Description

Outcomes

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.

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
to measure gefitinib levels with serum and cerebrospinal fluid while on therapy, and to correlate these levels with toxicity, response and survival
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.

Full Information

First Posted
September 6, 2006
Last Updated
January 29, 2018
Sponsor
David M. Jackman, MD
Collaborators
AstraZeneca, Massachusetts General Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT00372515
Brief Title
High Dose Gefitinib for the Treatment of Carcinomatous Meningitis in Adult Patients With Non-Small Cell Lung Cancer and Known or Suspected EGFR Mutations
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
June 2006 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
David M. Jackman, MD
Collaborators
AstraZeneca, Massachusetts General Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer
Keywords
epidermal growth factor, EGFR, lung cancer, Iressa, Gefitinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
High dose gefitinib
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Gefitinib
Other Intervention Name(s)
Iressa
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruce Johnson, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
25784657
Citation
Jackman DM, Cioffredi LA, Jacobs L, Sharmeen F, Morse LK, Lucca J, Plotkin SR, Marcoux PJ, Rabin MS, Lynch TJ, Johnson BE, Kesari S. A phase I trial of high dose gefitinib for patients with leptomeningeal metastases from non-small cell lung cancer. Oncotarget. 2015 Feb 28;6(6):4527-36. doi: 10.18632/oncotarget.2886.
Results Reference
result
Links:
URL
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=2886
Description
A Phase I trial of high dose gefitinib for patients with leptomeningeal metastases from non-small cell lung cancer

Learn more about this trial

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

We'll reach out to this number within 24 hrs