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

This study has been terminated.
(Slow accrual)
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00280748
First received: January 19, 2006
Last updated: June 22, 2017
Last verified: June 2017
  Purpose

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.


Condition Intervention Phase
Lung Cancer Metastatic Cancer Drug: pemetrexed disodium Radiation: radiation therapy Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • Response of Intracranial Metastases (Complete and Partial Response) [ Time Frame: 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:
  • Number of Subjects Experiencing Adverse Events [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.


Enrollment: 10
Study Start Date: May 2005
Study Completion Date: April 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Single Arm Study
Single Arm Study
Drug: pemetrexed disodium
500 mg/m2 once every 21 days up to 126 days
Other Name: Alimta
Radiation: radiation therapy
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

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00280748

Locations
United States, North Carolina
Alamance Oncology/Hematology Associates, LLP
Burlington, North Carolina, United States, 27216
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Thomas E. Stinchcombe, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00280748     History of Changes
Other Study ID Numbers: LCCC 0409
CDR0000551069 ( Other Identifier: PDQ number )
Study First Received: January 19, 2006
Results First Received: April 3, 2017
Last Updated: June 22, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
recurrent non-small cell lung cancer
stage IV non-small cell lung cancer
tumors metastatic to brain

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasm Metastasis
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplastic Processes
Pathologic Processes
Pemetrexed
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 17, 2017