Back to resultsWhole-Brain Radiation Therapy and Pemetrexed in Treating Patients With Brain Metastases From Non-Small Cell Lung Cancer (NRR)
Primary Purpose
Lung Cancer, Metastatic Cancer
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
pemetrexed disodium
radiation therapy
Sponsored by
About this trial
This is an interventional treatment trial for Lung Cancer focused on measuring recurrent non-small cell lung cancer, stage IV non-small cell lung cancer, tumors metastatic to brain
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
Sites / Locations
- Alamance Oncology/Hematology Associates, LLP
- Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Single Arm Study
Arm Description
Single Arm Study
Outcomes
Primary Outcome Measures
Response of Intracranial Metastases (Complete and Partial Response)
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
Number of Subjects Experiencing Adverse Events
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.
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.
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
A classification score defined as follows:
Able to work or to perform normal activities: neurological findings minor or absent
Able to carry out normal activities with minimal difficulties. Neurological impairment does not require nursing care or hospitalization
Seriously limited in performing normal activities. Requiring nursing care or hospitalization. Patients confined to bed or wheelchair or have significant intellectual impairment
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
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
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.
Full Information
NCT ID
NCT00280748
First Posted
January 19, 2006
Last Updated
June 22, 2017
Sponsor
UNC Lineberger Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00280748
Brief Title
Whole-Brain Radiation Therapy and Pemetrexed in Treating Patients With Brain Metastases From Non-Small Cell Lung Cancer
Acronym
NRR
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
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Terminated
Why Stopped
Slow accrual
Study Start Date
May 2005 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
April 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNC Lineberger Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer, Metastatic Cancer
Keywords
recurrent non-small cell lung cancer, stage IV non-small cell lung cancer, tumors metastatic to brain
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single Arm Study
Arm Type
Other
Arm Description
Single Arm Study
Intervention Type
Drug
Intervention Name(s)
pemetrexed disodium
Other Intervention Name(s)
Alimta
Intervention Description
500 mg/m2 once every 21 days up to 126 days
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Intervention Description
Patients will receive cranial irradiation at 2.5 Gy per fraction, 5 days a week, for 3 weeks to a total dose of 37.5 Gy
Primary Outcome Measure Information:
Title
Response of Intracranial Metastases (Complete and Partial Response)
Description
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.
Time Frame
126 days
Secondary Outcome Measure Information:
Title
Number of Subjects Experiencing Adverse Events
Description
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.
Time Frame
maximum 5 months
Title
Estimate the Overall Survival of Patients Treated With This Regimen.
Description
Patients were followed for survival from start of treatment until death from any cause (up to 4 years)
Time Frame
4 years
Title
Evaluate the Functional Status of Patients Treated With This Regimen.
Description
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.
Time Frame
baseline functional status only
Title
Neurological Function by Radiation Oncology Group (RTOG) Neurological Function Classification
Description
A classification score defined as follows:
Able to work or to perform normal activities: neurological findings minor or absent
Able to carry out normal activities with minimal difficulties. Neurological impairment does not require nursing care or hospitalization
Seriously limited in performing normal activities. Requiring nursing care or hospitalization. Patients confined to bed or wheelchair or have significant intellectual impairment
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.
Time Frame
At Baseline, 30 days, and at end of treatment (maximum 5 months).
Title
Neurological Function by Mini Mental State Examination
Description
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).
Time Frame
Baseline (pre-treatment), 30 days (Cycle 2 Day 1), and maximum 5 months (end of treatment).
Title
Response of Patients With Extracranial Disease Treated With Pemetrexed
Description
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.
Time Frame
maximum 5 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas E. Stinchcombe, MD
Organizational Affiliation
UNC Lineberger Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Alamance Oncology/Hematology Associates, LLP
City
Burlington
State/Province
North Carolina
ZIP/Postal Code
27216
Country
United States
Facility Name
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7295
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://clinicaltrials.gov/ct2/show/NCT00280748
Description
Clinical trial summary from the National Cancer Institute's PDQ® database
Learn more about this trial
Whole-Brain Radiation Therapy and Pemetrexed in Treating Patients With Brain Metastases From Non-Small Cell Lung Cancer
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