Whole-Brain Radiation Therapy and Pemetrexed in Treating Patients With Brain Metastases From Non-Small Cell Lung Cancer

Phase 2

Terminated

Conditions: Lung Cancer
Metastatic Cancer

Interventions: Drug: pemetrexed disodium
Radiation: radiation therapy

Registration Number: NCT00280748

Lead Sponsor: UNC Lineberger Comprehensive Cancer Center

Brief Summary: RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving radiation therapy together with pemetrexed may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving whole-brain radiation therapy together with pemetrexed works in treating patients with brain metastases from non-small cell lung cancer.

Detailed Description: OBJECTIVES:

Primary

* Estimate the response in patients with intracranial brain metastases from non-small cell lung cancer treated with whole-brain radiotherapy and pemetrexed disodium.

Secondary

* Determine the toxicity of this regimen in these patients.

* Estimate the overall survival of patients treated with this regimen.

* Evaluate the functional status of patients treated with this regimen.

* Assess neurological function and progression in patients treated with this regimen.

* Determine the response of patients with extracranial disease treated with pemetrexed disodium.

OUTLINE: Patients undergo whole-brain radiotherapy 5 days a week for 3 weeks beginning on day 1. Patients also receive pemetrexed disodium IV on day 1, 2, or 3 and day 28 of course 1, and on day 1 of each subsequent course. Treatment with pemetrexed disodium repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 30 days and then every 2 months for 2 years.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 10

Inclusion Criteria

Karnofsky performance status 70-100% OR ≥ 70 years of age
Life expectancy > 3 months
Absolute neutrophil count (ANC) > 1,500/mm³
Platelet count > 100,000/mm³
Hemoglobin ≥ 8 g/dL
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times upper limit of normal (ULN)
Bilirubin ≤ 1.5 times ULN
Creatinine clearance ≥ 45 mL/min
Able to take vitamins, folic acid, and corticosteroids

Exclusion Criteria

Contraindication or intolerance to corticosteroid therapy
Other malignancies within the past 5 years and disease-free OR prognosis is best defined by the NSCLC in the opinion of the attending physician
Pregnant or nursing
Positive pregnancy test
Fertile patients must use effective contraception
HIV positive
Severe hypersensitivity to pemetrexed disodium
Unable to discontinue NSAIDs for ≥ 5 days
History of underlying dementia, Parkinson's disease, or Alzheimer's disease

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single Arm Study	radiation therapy	Single Arm Study
Single Arm Study	pemetrexed disodium	Single Arm Study

Primary Outcome Measures

Name	Time	Method
Response of Intracranial Metastases (Complete and Partial Response)	126 days	Radiographic response will be measured by RECIST, Response Evaluation Criteria In Solid Tumors Criteria, indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects Experiencing Adverse Events	maximum 5 months	Toxicities was assessed using Common Terminology Criteria for Adverse Events (CTCAE) grading scale. Only toxicities with attribution to chemotherapy of "definite" or "probable" are considered, as determined by treating physician.
Estimate the Overall Survival of Patients Treated With This Regimen.	4 years	Patients were followed for survival from start of treatment until death from any cause (up to 4 years)
Evaluate the Functional Status of Patients Treated With This Regimen.	baseline functional status only	Functional status evaluated using the Karnofsky functional status scale. The Karnofsky Performance Scale (KPS) Index allows patients to be classified as to their functional impairment. This can be used to compare effectiveness of different therapies and to assess the prognosis in individual patients. The lower the Karnofsky score, the worse the survival for most serious illnesses. The Karnofsky score runs from 100 to 0, where 100 is "perfect" health and 0 is death.
Neurological Function by Radiation Oncology Group (RTOG) Neurological Function Classification	At Baseline, 30 days, and at end of treatment (maximum 5 months).	A classification score defined as follows: 1. Able to work or to perform normal activities: neurological findings minor or absent 2. Able to carry out normal activities with minimal difficulties. Neurological impairment does not require nursing care or hospitalization 3. Seriously limited in performing normal activities. Requiring nursing care or hospitalization. Patients confined to bed or wheelchair or have significant intellectual impairment 4. Unable to perform even minimal normal activities. Requiring hospitalization and constant nursing care and feeding. Patients unable to communicate or in coma.A higher score indicates worse function.
Neurological Function by Mini Mental State Examination	Baseline (pre-treatment), 30 days (Cycle 2 Day 1), and maximum 5 months (end of treatment).	The Mini Mental State Examination is a 30-point questionnaire that is used to measure cognitive impairment. Score totals range from normal cognition (24-30 points), mild impairment (19-23 points), moderate impairment (10-18 points), to severe impairment (≤9 points).
Response of Patients With Extracranial Disease Treated With Pemetrexed	maximum 5 months	Response was measured by Response Evaluation Criteria In Solid Tumors RECIST criteria v1.0. Complete Response (CR) - Disappearance of all lesions Partial Response (PR) - at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Stable Disease (SD) - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started. Progressive Disease (PD) - at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing nontarget lesions.

Trial Locations

Locations (2): Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
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Chapel Hill, North Carolina, United States
Alamance Oncology/Hematology Associates, LLP
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Burlington, North Carolina, United States