Stereotactic Radiosurgery and Erlotinib in Treating Patients With Non-Small Cell Lung Cancer and Brain Metastases - Full Text View

Sponsored by:	UCSF Helen Diller Family Comprehensive Cancer Center
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00738335

Purpose

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.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors Lung Cancer	Drug: erlotinib hydrochloride Other: immunoenzyme technique Other: laboratory biomarker analysis Other: liquid chromatography Other: mass spectrometry Other: pharmacological study Radiation: stereotactic radiosurgery	Phase I

MedlinePlus related topics: Cancer Lung Cancer Radiation Therapy

Drug Information available for: Erlotinib hydrochloride Erlotinib

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Acute and long-term toxicity (i.e., neurotoxicity, gastrointestinal, cutaneous, and hematologic) as assessed by NCI CTCAE v3.0. [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Disease progression [ Designated as safety issue: No ]
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 [ Designated as safety issue: No ]
CNS progression at 1 year [ Designated as safety issue: No ]
Distribution of erlotinib hydrochloride in plasma and cerebrospinal fluid (CSF) [ Designated as safety issue: No ]
CSF and serum biomarkers [ Designated as safety issue: No ]
Incidence of subclinical leptomeningeal disease [ Designated as safety issue: No ]

Estimated Enrollment:	54
Study Start Date:	January 2009
Estimated Primary Completion Date:	August 2012 (Final data collection date for primary outcome measure)

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.

Eligibility

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

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00738335

Locations

United States, California
UCSF Helen Diller Family Comprehensive Cancer Center	Recruiting
San Francisco, California, United States, 94115
Contact: Clinical Trials Office - UCSF Helen Diller Family Comprehensi 877-827-3222

Sponsors and Collaborators

UCSF Helen Diller Family Comprehensive Cancer Center

Investigators

Principal Investigator:

James L. Rubenstein, MD, PhD

UCSF Helen Diller Family Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000612064, UCSF-072520, CC# 072520, GENENTECH-UCSF-072520
Study First Received:	August 19, 2008
Last Updated:	February 26, 2009
ClinicalTrials.gov Identifier:	NCT00738335 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage IV non-small cell lung cancer
adult tumors metastatic to brain
recurrent non-small cell lung cancer

Study placed in the following topic categories:

Erlotinib
Thoracic Neoplasms
Central Nervous System Neoplasms
Protein Kinase Inhibitors
Recurrence
Carcinoma
Signs and Symptoms
Respiratory Tract Diseases

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

Additional relevant MeSH terms:

Erlotinib
Thoracic Neoplasms
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Nervous System Diseases
Enzyme Inhibitors
Central Nervous System Neoplasms
Protein Kinase Inhibitors
Pharmacologic Actions
Carcinoma

Neoplastic Processes
Neoplasms
Pathologic Processes
Neoplasms by Site
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Neoplasm Metastasis
Carcinoma, Non-Small-Cell Lung
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 06, 2009