Clinical trial NCT00280748: Whole-Brain Radiation Therapy and Pemetrexed in Treating Patients With Brain Metastases From Non-Small Cell Lung Cancer
Official title: A Phase II Study of Treatment of Brain Metastases From Non-Small Cell Lung Cancer With Concurrent Whole Brain Radiation Therapy and Pemetrexed
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lung Cancer
Metastatic Cancer
Keywords: recurrent non-small cell lung cancer
stage IV non-small cell lung cancer
tumors metastatic to brain
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-01-23
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)
* Must have evidence of brain metastases by MRI or CT scan

PRIOR CONCURRENT THERAPY:

* Recovered from prior oncologic or major surgery
* Prior resection of all brain metastases or only site of brain metastases allowed provided there is radiologically evaluable intracranial metastases
* No prior cranial irradiation, including stereotactic radiosurgery
* More than 30 days since prior non-approved or investigational drug
* No other concurrent chemotherapy, immunotherapy, hormonal therapy, radiotherapy, surgery, or experimental medications

  * No single brain metastases or oligometastatic disease amenable to surgical resection or radiosurgery
* Relapsed NSCLC with brain metastases allowed
* Not a candidate for double-agent or platinum-based chemotherapy
* No leptomeningeal metastases
* No clinically relevant (defined by physical exam) pleural effusions or ascites that cannot be controlled with drainage or other procedures

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

Primary outcomes:
measure: Response of Intracranial Metastases (Complete and Partial Response)
timeFrame: 126 days
Secondary outcomes:
measure: Number of Subjects Experiencing Adverse Events
timeFrame: maximum 5 months
measure: Estimate the Overall Survival of Patients Treated With This Regimen.
timeFrame: 4 years
measure: Evaluate the Functional Status of Patients Treated With This Regimen.
timeFrame: baseline functional status only
measure: Neurological Function by Radiation Oncology Group (RTOG) Neurological Function Classification
timeFrame: At Baseline, 30 days, and at end of treatment (maximum 5 months).
measure: Neurological Function by Mini Mental State Examination
timeFrame: Baseline (pre-treatment), 30 days (Cycle 2 Day 1), and maximum 5 months (end of treatment).
measure: Response of Patients With Extracranial Disease Treated With Pemetrexed
timeFrame: maximum 5 months
Other outcomes:
Locations:
city: Burlington
country: United States
facility: Alamance Oncology/Hematology Associates, LLP
state: North Carolina
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Thomas E. Stinchcombe, MD
role: PRINCIPAL_INVESTIGATOR
References: