Lung CancerPhase 1NCT00738335
Stereotactic Radiosurgery and Erlotinib in Treating Patients With Non-Small Cell Lung Cancer and Brain Metastases
A Phase 1 study testing erlotinib hydrochloride, immunoenzyme technique and laboratory biomarker analysis in people with Lung Cancer and Metastatic Cancer, run by University of California, San Francisco at 1 site in United States.
Trial summary
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Stereotactic radiosurgery may be able to deliver x-rays directly to the tumor and cause less damage to normal tissue. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer, Metastatic Cancer
- What is being tested?
- erlotinib hydrochloride, immunoenzyme technique and laboratory biomarker analysis
- Type of treatment
- Surgery or procedure
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2009to Jul 2009
- 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
DISEASE CHARACTERISTICS:
- Histologically confirmed non-small cell lung cancer (NSCLC) meeting the following criteria:
- Fewer than 5 intraparenchymal brain metastases by gadolinium-enhanced MRI meeting the following criteria:
- Maximum diameter ≤ 4.0 cm
- If multiple lesions are present and one lesion is > 3.0 cm, the remaining lesions must be ≤ 3.0 cm in maximum diameter
- No metastases within 3 mm of the optic nerve or optic chiasm such that some portion of the optic nerve or chiasm would receive > 9 Gy from radiosurgery
- No metastases in the brainstem, midbrain, pons, or medulla
- No prior complete resection of a single brain metastasis or of all known brain metastases
- Subtotal resection allowed provided residual disease is ≤ 4.0 cm in maximum diameter
- No clinical or radiographic evidence of unstable systemic progression (other than the study lesion[s]) within the past month
- Patients with brain metastases at initial presentation do not require 1 month of scans documenting stable disease
- Isolated brain metastases with stable systemic disease allowed
- No leptomeningeal metastases by MRI and/or positive cerebrospinal fluid cytology
PATIENT CHARACTERISTICS:
- Karnofsky performance status 60-100%
- Life expectancy ≥ 3 months
- ANC > 1,000/mm³
- Platelet count > 100,000/mm³
- Hemoglobin > 10 g/dL
- PT and PTT normal
- AST < 2 times upper limit of normal (ULN)
- Alkaline phosphatase < 2 times ULN
- Total bilirubin < 2 times ULN
- Lactic dehydrogenase < 2 times ULN
- Serum creatinine < 1.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for ≥ 2 weeks after completion of study therapy
- Neurologic function status 0-2
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib hydrochloride
- No contraindication to MRI (e.g., cardiac pacemaker)
- No absolute contraindication to lumbar puncture
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Prior systemic therapy allowed
- No prior cranial radiotherapy
- Prior radiotherapy to noncranial sites allowed
- More than 1 week since prior intrathecal chemotherapy or prior treatment of leptomeningeal carcinoma
- No concurrent systemic therapy
- Prior or current erlotinib hydrochloride for treatment of systemic disease allowed provided systemic disease has not progressed while on erlotinib hydrochloride
- No concurrent enzyme-inducing anticonvulsant
- If patients are on an enzyme-inducing anticonvulsant (e.g., phenytoin, carbamazepine, or phenobarbital), the agent must be converted to a nonenzyme-inducing anticonvulsant before or at the start of erlotinib hydrochloride treatment
- No concurrent CYP3A4 inhibitors or inducers (e.g., Hypericum perforatum [St. John wort] or ketoconazole)
- No other concurrent investigational therapy
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115
About this study
Official title: A Phase I Open-Label, Dose-Finding Study to Evaluate the Safety and Efficacy of Concurrent Radiosurgery and Erlotinib Administration in Non-Small Cell Lung Cancer Patients With Brain Metastases
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Stereotactic radiosurgery may be able to deliver x-rays directly to the tumor and cause less damage to normal tissue. Erlotinib may make tumor cells more sensitive to radiation therapy. Giving erlotinib together with stereotactic radiosurgery may kill more tumor cells.
PURPOSE: This phase I clinical trial is studying the side effects of erlotinib when given together with stereotactic radiosurgery and to see how well it works in treating patients with non-small cell lung cancer with brain metastases.
Read the detailed description
OBJECTIVES:
Primary
- To determine the acute as well as long-term toxicity (especially grade III neurotoxicity) of concurrent erlotinib hydrochloride and single-fraction radiosurgery in patients with non-small cell lung cancer (NSCLC) and brain metastases.
Secondary
- To determine the freedom from progression in all detected lesions (i.e., radiosurgically treated and untreated) and the rate of response of radiosurgically treated lesions in patients receiving concurrent erlotinib hydrochloride and radiosurgery as compared with historical controls treated with gamma knife radiosurgery alone at UCSF.
- To measure the rate of freedom from any CNS progression in these patients at 1 year post treatment.
- To assess cerebrospinal fluid (CSF) distribution of erlotinib hydrochloride by measuring both erlotinib hydrochloride and its major metabolite, OSI-420, in plasma and CSF at 4 or more days after initial erlotinib hydrochloride administration but before radiosurgery, and again at 4 weeks after stereotactic radiosurgery (optional).
- To perform CSF and serum biomarker analysis for NSCLC using 2-dimensional liquid chromatography or mass spectrometry (2D-LC/MS).
- To determine the incidence of subclinical leptomeningeal disease in patients assigned to gamma-knife treatment and who do not exhibit signs or symptoms or carcinomatous meningitis.
OUTLINE: Patients receive oral erlotinib hydrochloride once daily for at least 7 days. Patients then undergo stereotactic radiosurgery on day 0. Beginning the day after radiosurgery, patients receive erlotinib hydrochloride once daily for 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients may continue to receive erlotinib hydrochloride at the discretion of their oncologist.
Patients undergo cerebrospinal fluid (CSF) and blood sample collection at baseline (at least 4 days after starting erlotinib hydrochloride and prior to radiosurgery) for pharmacokinetic and biomarker correlative studies. Samples are analyzed for concentrations of erlotinib hydrochloride by 2-dimensional-liquid chromatography/mass spectrometry and antithrombin by enzyme-linked immunosorbent assay.
After completion of study therapy, patients are followed every 3 months for 1 year.
- Conditions
- Lung Cancer, Metastatic Cancer
- Being tested
- erlotinib hydrochloride, immunoenzyme technique, laboratory biomarker analysis, liquid chromatography, mass spectrometry
- Keywords
- stage IV non-small cell lung cancer, tumors metastatic to brain, recurrent non-small cell lung cancer
- Medical subject headings
- Lung Neoplasms, Neoplasm Metastasis, Carcinoma, Non-Small-Cell Lung, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
erlotinib hydrochlorideDrug
immunoenzyme techniqueOther
laboratory biomarker analysisOther
liquid chromatographyOther
mass spectrometryOther
stereotactic radiosurgeryRadiation
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute and long-term toxicity (i.e., neurotoxicity, gastrointestinal, cutaneous, and hematologic) as assessed by NCI CTCAE v3.0.
Secondary outcomes (6)
Disease progression
Response rate of radiosurgically treated lesions in patients receiving concurrent erlotinib hydrochloride and radiosurgery on this study vs the response rate of historical controls previously treated with gamma knife radiosurgery alone
CNS progression at 1 year
Distribution of erlotinib hydrochloride in plasma and cerebrospinal fluid (CSF)
CSF and serum biomarkers
Incidence of subclinical leptomeningeal disease
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2008 (estimated)
- Study startJan 2009
- Primary completionJul 2009
- Study completionJul 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- James L. Rubenstein, MD, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00738335
- Sponsor's protocol ID
- CDR0000612064
- Other IDs
- UCSF-072520, CC# 072520, GENENTECH-UCSF-072520
- Status last verified
- Oct 2012
- First submitted
- 19 Aug 2008
- Last updated
- 4 Oct 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Open-Label, Dose-Finding Study to Evaluate the Safety and Efficacy of Concurrent Radiosurgery and Erlotinib Administration in Non-Small Cell Lung Cancer Patients With Brain Metastases
- ClinicalTrials.gov ID
- NCT00738335
- Acronym / sponsor ID
- CDR0000612064
- Conditions
- Lung Cancer, Metastatic Cancer
- Keywords
- stage IV non-small cell lung cancer, tumors metastatic to brain, recurrent non-small cell lung cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- Jan 2009
- Primary completion
- Jul 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 20 Aug 2008 (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.
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Stereotactic radiosurgery may be able to deliver x-rays directly to the tumor and cause less damage to normal tissue. Erlotinib may make tumor cells more sensitive to radiation therapy. Giving erlotinib together with stereotactic radiosurgery may kill more tumor cells.
PURPOSE: This phase I clinical trial is studying the side effects of erlotinib when given together with stereotactic radiosurgery and to see how well it works in treating patients with non-small cell lung cancer with brain metastases.
Detailed description
OBJECTIVES:
Primary
- To determine the acute as well as long-term toxicity (especially grade III neurotoxicity) of concurrent erlotinib hydrochloride and single-fraction radiosurgery in patients with non-small cell lung cancer (NSCLC) and brain metastases.
Secondary
- To determine the freedom from progression in all detected lesions (i.e., radiosurgically treated and untreated) and the rate of response of radiosurgically treated lesions in patients receiving concurrent erlotinib hydrochloride and radiosurgery as compared with historical controls treated with gamma knife radiosurgery alone at UCSF.
- To measure the rate of freedom from any CNS progression in these patients at 1 year post treatment.
- To assess cerebrospinal fluid (CSF) distribution of erlotinib hydrochloride by measuring both erlotinib hydrochloride and its major metabolite, OSI-420, in plasma and CSF at 4 or more days after initial erlotinib hydrochloride administration but before radiosurgery, and again at 4 weeks after stereotactic radiosurgery (optional).
- To perform CSF and serum biomarker analysis for NSCLC using 2-dimensional liquid chromatography or mass spectrometry (2D-LC/MS).
- To determine the incidence of subclinical leptomeningeal disease in patients assigned to gamma-knife treatment and who do not exhibit signs or symptoms or carcinomatous meningitis.
OUTLINE: Patients receive oral erlotinib hydrochloride once daily for at least 7 days. Patients then undergo stereotactic radiosurgery on day 0. Beginning the day after radiosurgery, patients receive erlotinib hydrochloride once daily for 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients may continue to receive erlotinib hydrochloride at the discretion of their oncologist.
Patients undergo cerebrospinal fluid (CSF) and blood sample collection at baseline (at least 4 days after starting erlotinib hydrochloride and prior to radiosurgery) for pharmacokinetic and biomarker correlative studies. Samples are analyzed for concentrations of erlotinib hydrochloride by 2-dimensional-liquid chromatography/mass spectrometry and antithrombin by enzyme-linked immunosorbent assay.
After completion of study therapy, patients are followed every 3 months for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| erlotinib hydrochloride | Drug | – |
| immunoenzyme technique | Other | – |
| laboratory biomarker analysis | Other | – |
| liquid chromatography | Other | – |
| mass spectrometry | Other | – |
| pharmacological study | Other | – |
| stereotactic radiosurgery | Radiation | – |
Primary outcome
Acute and long-term toxicity (i.e., neurotoxicity, gastrointestinal, cutaneous, and hematologic) as assessed by NCI CTCAE v3.0.
6 secondary outcomes
Disease progression
Response rate of radiosurgically treated lesions in patients receiving concurrent erlotinib hydrochloride and radiosurgery on this study vs the response rate of historical controls previously treated with gamma knife radiosurgery alone
CNS progression at 1 year
Distribution of erlotinib hydrochloride in plasma and cerebrospinal fluid (CSF)
CSF and serum biomarkers
Incidence of subclinical leptomeningeal disease
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2012.
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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.
James L. Rubenstein, MD, PhD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing erlotinib hydrochloride, immunoenzyme technique and laboratory biomarker analysis in people with Lung Cancer and Metastatic Cancer, run by University of California, San Francisco at 1 site 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?
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: withdrawn, as of the sponsor's last update on 4 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 was withdrawn before enrolling participants, so there are no results.
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?
Acute and long-term toxicity (i.e., neurotoxicity, gastrointestinal, cutaneous, and hematologic) as assessed by NCI CTCAE v3.0.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Oct 2012.