Non-Small Cell Lung CancerPhase 1NCT00372515
High Dose Gefitinib for the Treatment of Carcinomatous Meningitis in Adult Patients With Non-Small Cell Lung Cancer and Known or Suspected EGFR Mutations
A Phase 1 study testing Gefitinib in people with Non-Small Cell Lung Cancer, run by David M. Jackman, MD at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- Gefitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 2 sitesUnited States
- Study dates
- Jun 2006to Apr 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this 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
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.
Read the 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.
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- Gefitinib
- Keywords
- epidermal growth factor, EGFR, lung cancer, Iressa, Gefitinib
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GefitinibDrug
Also called Iressa
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.
| Study group | Role | What they receive |
|---|---|---|
| High dose gefitinib | Experimental | Not described Receives: Drug: Gefitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Secondary outcomes (3)
To measure the cytologic response rate, response duration, time to neurologic progression, and survival following high dose gefitinib therapy administered on this schedule
Measured: 2 years
to measure gefitinib levels with serum and cerebrospinal fluid while on therapy, and to correlate these levels with toxicity, response and survival
Measured: 2 years
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2006 (estimated)
- Study startJun 2006
- Primary completionDec 2012
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- David M. Jackman, MD
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, Massachusetts General Hospital
- Responsible party
- Sponsor-investigator, David M. Jackman, MD, Dana-Farber Cancer Institute
- Investigators
- Bruce Johnson, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00372515
- Sponsor's protocol ID
- 05-403
- Status last verified
- Jan 2018
- First submitted
- 6 Sep 2006
- Last updated
- 31 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 25784657
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00372515
- Acronym / sponsor ID
- 05-403
- Conditions
- Non-Small Cell Lung Cancer
- Keywords
- epidermal growth factor, EGFR, lung cancer, Iressa, Gefitinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- David M. Jackman, MDUniversity, hospital or other
- Collaborators
- AstraZeneca, Massachusetts General Hospital
- Study start
- Jun 2006
- Primary completion
- Dec 2012 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 7 Sep 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| High dose gefitinib | Experimental | Drug: Gefitinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GefitinibAlso: IressaOn 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. | Drug | High dose gefitinib |
Primary outcome
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
3 secondary outcomes
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2018.
- Results publication: PubMed 25784657Jackman 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruce Johnson, MD principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gefitinib in people with Non-Small Cell Lung Cancer, run by David M. Jackman, MD at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00372515, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2018.