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

Sponsors and Collaborators:	Cancer Institute of New Jersey National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00385398

Purpose

RATIONALE: Treatment with radiosurgery, temozolomide, and erlotinib may affect brain function (the ability to think, learn, remember, and judge) in patients with non-small cell lung cancer and brain metastases. A study that evaluates brain function may help doctors plan the best treatment.

PURPOSE: This phase II trial is studying the effect of radiosurgery, temozolomide, and erlotinib on brain function in patients with non-small cell lung cancer and brain metastases.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors Lung Cancer	Drug: erlotinib hydrochloride Drug: temozolomide Procedure: DNA methylation analysis Procedure: cognitive assessment Procedure: management of therapy complications Procedure: quality-of-life assessment Procedure: stereotactic radiosurgery	Phase II

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Temozolomide Erlotinib Erlotinib hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Phase II Study of Stereotactic Radiosurgery, Temozolomide and Erlotinib Chemotherapy for the Treatment of 1-3 Brain Metastases in Non-Small Cell Lung Cancer

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

Primary Outcome Measures:

Cognitive function [ Designated as safety issue: No ]

Secondary Outcome Measures:

Tumor response [ Designated as safety issue: No ]
Time to tumor progression in brain [ Designated as safety issue: No ]
Survival [ Designated as safety issue: No ]
Quality of life as measured by FACT subscale [ Designated as safety issue: No ]
Physical functioning as measured by Karnofsky performance status and Katz index of activities of daily living [ Designated as safety issue: No ]
Frequency of O6-methylguanine-DNA methyltransferase promoter methylation [ Designated as safety issue: No ]

Estimated Enrollment:	54
Study Start Date:	April 2006

Detailed Description:

OBJECTIVES:

Primary

Determine the effect of stereotactic radiosurgery, temozolomide, and erlotinib hydrochloride on cognitive function in patients with non-small cell lung cancer and brain metastases.

Secondary

Determine the feasibility and safety of this regimen, in terms of tumor response, time to tumor progression in brain, survival, physical functioning, and quality of life, in these patients.
Determine the frequency of O6-methylguanine-DNA methyltransferase promoter methylation in these patients.

OUTLINE: This is a multicenter study.

Patients undergo stereotactic radiosurgery on day -7. Patients receive oral temozolomide once daily on days 1-5 and oral erlotinib hydrochloride once daily on days 1-23. Treatment with temozolomide and erlotinib hydrochloride repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo cognitive function evaluation as measured by Mini-Mental Status Exam administration and scoring; quality of life assessment as measured by Functional Assessment of Cancer Therapy subscale; and physical functioning assessment as measured by Katz index of activities of daily living and Karnofsky performance status at baseline and then every 8 weeks during study treatment.

Tumor tissue is examined by O6-methylguanine-DNA methyltransferase (MGMT gene) promotor methylation.

After completion of study therapy, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.

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 meeting the following criteria:
- One to 3 brain metastases, meeting the following criteria:
  - No larger than 3 cm
  - Greater than 5 mm from the optic apparatus
  - Not involving the brainstem, pons, medulla, or midbrain
- Stable systemic disease for the past 3 months
  - Less than 3 months since completion of primary treatment
Measurable CNS disease as defined by RECIST criteria
No leptomeningeal disease documented by MRI or cerebrospinal fluid cytologic evaluation

PATIENT CHARACTERISTICS:

Life expectancy ≥ 12 weeks
Karnofsky performance status 60-100%
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 10 g/dL
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST ≤ 3.0 times ULN
Serum creatinine ≤ 1.5 mg/dL
Creatinine clearance > 50 mL/min
No other malignancy within the past 5 years, except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
No concurrent major medical illness or psychiatric impairment that, in the investigator's opinion, would preclude study participation
No concurrent active infections
No known HIV positivity
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective nonhormonal contraception during and for 3 months after completion of study treatment

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior complete resection of all brain metastases
No prior brain radiation therapy
No prior temozolomide or erlotinib hydrochloride
No concurrent enzyme-inducing anti-epileptic drugs
No concurrent recombinant interleukin-11
No other concurrent anticancer investigational or commercial agents or therapies, including chemotherapy, immunotherapy, hormonal cancer therapy, radiation therapy, or cancer surgery
No concurrent enrollment on another clinical trial
Surgery for symptomatic brain lesions prior to radiosurgery allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00385398

Sponsors and Collaborators

Cancer Institute of New Jersey

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Molly Gabel, MD

Cancer Institute of New Jersey

More Information

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

Study ID Numbers:	CDR0000539474, CINJ-030601, CINJ-0220060108, CINJ-NJ1506
Study First Received:	October 5, 2006
Last Updated:	October 22, 2008
ClinicalTrials.gov Identifier:	NCT00385398
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Thoracic Neoplasms
Erlotinib
Non-small cell lung cancer
Central Nervous System Neoplasms
Temozolomide
Carcinoma
Respiratory Tract Diseases

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

Additional relevant MeSH terms:

Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Nervous System Diseases
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

Neoplasms
Neoplastic Processes
Neoplasms by Site
Pathologic Processes
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009