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Temozolomide and Radiation Therapy in Treating Patients With Brain Metastasis Secondary to Non-Small Cell Lung Cancer

Primary Purpose

Lung Cancer, Metastatic Cancer

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Temozolomide
Radiation therapy
Sponsored by
Eastern Cooperative Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

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, squamous cell lung cancer, adenocarcinoma of the lung, large cell lung cancer, bronchoalveolar cell lung cancer, adenosquamous cell lung cancer, tumors metastatic to brain

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Histologically confirmed non-small cell lung cancer (NSCLC), including the following histologies: Squamous cell carcinoma Adenocarcinoma Large cell carcinoma Bronchoalveolar carcinoma All variants of NSCLC At least 1 bidimensionally measurable brain metastasis Confirmed by MRI within the past two weeks, and computed tomography (CT) scan is not acceptable Biopsy is not required Not eligible for surgical resection or radiosurgery of brain metastasis Systemic disease not in immediate need of chemotherapy Age>=18 years ECOG Performance status of 0-1 More than 12 weeks of life expectancy Adequate hematologic, renal, and liver function as demonstrated by laboratory values performed within two weeks, inclusive, prior to administration of study drug or registration Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10 g/dL Bilirubin ≤ 2 times upper limit of normal (ULN) Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2 times upper limit of normal (5 times ULN if liver metastases are present) Alkaline phosphatase ≤ 2 times ULN (5 times ULN if liver metastases are present) Creatinine ≤ 1.6 mg/dL Fertile patients must use effective contraception Prior biologic therapy allowed More than 4 weeks since prior chemotherapy Prior radiotherapy for local control or palliative therapy for painful bony lesions allowed Prior surgery for brain metastasis allowed At least 4 weeks since prior radiotherapy to ≥ 15% of bone marrow (2 weeks for < 15% of bone marrow) and recovered No prior radiotherapy to ≥ 50% of bone marrow Concurrent radiotherapy to painful bony lesions allowed provided no more than 15% of bone marrow is irradiated Exclusion Criteria: HIV positive AIDS-related illness Poor medical risks due to active nonmalignant systemic disease Frequent vomiting There is medical condition that would interfere with oral medication intake (e.g., partial bowel obstruction) Pregnant or nursing Prior temozolomide Prior radiotherapy to the brain, including stereotactic radiosurgery to a different lesion Concurrent intensity modulated radiotherapy or 3-D cranial radiotherapy Other concurrent investigational agents Other concurrent treatment for brain metastasis Other concurrent chemotherapy during study radiotherapy Concurrent growth factors to induce elevations in blood counts for the purposes of administration of study drug at scheduled dosing interval or to allow treatment with study drug at a higher dose

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Temozolomide and Radiation

    Arm Description

    Temozolomide:administered orally. Radiation: whole brain radiation therapy

    Outcomes

    Primary Outcome Measures

    Number of Patients With Intracranial Response
    Response was assessed per Response Evaluation Criteria in Solid Tumor (RECIST) by brain MRI in the 21 eligible and treated patients.Complete response (CR): complete disappearance of the clinically detectable malignant brain metastasis(es) being followed on MRI scan off corticosteroids and a stable or improving neurologic exam. Partial response (PR): greater than or equal to a 50% reduction in the sum of the product(s) of the maximal cross-sections on MRI scan with a stable or decreasing dose of corticosteroids and a stable or improving neurologic exam. Response = CR + PR

    Secondary Outcome Measures

    1-year Neurologic (Central Nervous System, CNS) Progression Free Rate
    1-year CNS progression free rate is the percentage of patients who had no CNS progression after being followed for 1 year . Progressive disease (CNS) was defined as a 25% or greater increase in the sum of the product(s) of the maximal cross-sections on MRI scan, reappearance of any lesion that has disappeared, development of any new lesion(s), stable disease with a deterioration of neurologic exam, or clear worsening of any evaluable disease.
    Time to Non-CNS (Systemic) Progression
    Time to non-CNS progression was calculated from time of protocol entry to time of first systemic progressive disease or death. Patients alive and non-CNS progression-free at last follow-up were censored. Disease progression was defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter (per RECIST criteria). Development of new lesions in non-CNS sites also constituted non-CNS progression. The 21 eligible and treated patients were included in the analysis.
    Overall Survival Time
    Overall survival (months) was calculated from time of protocol entry to time of death from any cause. Patients alive at last follow-up were censored. The 21 eligible and treated patients were included in the analysis.

    Full Information

    First Posted
    April 7, 2004
    Last Updated
    June 14, 2023
    Sponsor
    Eastern Cooperative Oncology Group
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00080938
    Brief Title
    Temozolomide and Radiation Therapy in Treating Patients With Brain Metastasis Secondary to Non-Small Cell Lung Cancer
    Official Title
    A Phase II Study of Temozolomide and Radiation Therapy in Patients With Brain Metastasis From Non-small Cell Lung Cancer (NSCLC)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2023
    Overall Recruitment Status
    Completed
    Study Start Date
    December 20, 2005 (Actual)
    Primary Completion Date
    August 2008 (Actual)
    Study Completion Date
    February 2009 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Eastern Cooperative Oncology Group
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as temozolomide may make the tumor cells more sensitive to radiation therapy. Combining temozolomide with radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving temozolomide together with whole-brain radiation therapy works in treating patients with brain metastasis secondary to non-small cell lung cancer.
    Detailed Description
    OBJECTIVES: Primary Determine the intracranial response rate in patients with brain metastasis secondary to non-small cell lung cancer treated with whole brain radiotherapy and temozolomide. Secondary Determine the time to radiological progression in patients treated with this regimen. Determine the time to neurological progression (confirmed by magnetic resonance imaging (MRI)) in patients treated with this regimen. Determine the overall survival of patients treated with this regimen. Determine the toxicity of this regimen in these patients. OUTLINE: This is a multicenter study. Patients undergo whole brain radiotherapy once daily, 5 days a week, for 2 weeks (10 fractions). Patients also receive concurrent oral temozolomide once daily on days 1-14. Beginning 3 weeks after the completion of chemoradiotherapy, patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of neurologic (Central Nervous System, CNS) progression or unacceptable toxicity. Patients were followed every 3 months for 2 years. ACCRUAL: A total of 26 patients were accrued for this study.

    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, squamous cell lung cancer, adenocarcinoma of the lung, large cell lung cancer, bronchoalveolar cell lung cancer, adenosquamous 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
    26 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Temozolomide and Radiation
    Arm Type
    Experimental
    Arm Description
    Temozolomide:administered orally. Radiation: whole brain radiation therapy
    Intervention Type
    Drug
    Intervention Name(s)
    Temozolomide
    Other Intervention Name(s)
    Temodar
    Intervention Description
    Temozolomide (TMZ) to be given at a dose of 75 mg/m2/day for 14 days, starting on D1 of whole brain radiotherapy (WBRT). Three weeks after completion of WBRT, TMZ will be given at a dose of 200 mg/m2/day x 5 days (or 150 mg/m2/day if prior chemotherapy) every 28-days,for an additional two cycles.
    Intervention Type
    Radiation
    Intervention Name(s)
    Radiation therapy
    Other Intervention Name(s)
    Whole brain radiation therapy
    Intervention Description
    Standard whole brain radiation therapy 30 Gy in ten fractions.
    Primary Outcome Measure Information:
    Title
    Number of Patients With Intracranial Response
    Description
    Response was assessed per Response Evaluation Criteria in Solid Tumor (RECIST) by brain MRI in the 21 eligible and treated patients.Complete response (CR): complete disappearance of the clinically detectable malignant brain metastasis(es) being followed on MRI scan off corticosteroids and a stable or improving neurologic exam. Partial response (PR): greater than or equal to a 50% reduction in the sum of the product(s) of the maximal cross-sections on MRI scan with a stable or decreasing dose of corticosteroids and a stable or improving neurologic exam. Response = CR + PR
    Time Frame
    assessed every cycle while on treatment, then every 3 months for 2 years
    Secondary Outcome Measure Information:
    Title
    1-year Neurologic (Central Nervous System, CNS) Progression Free Rate
    Description
    1-year CNS progression free rate is the percentage of patients who had no CNS progression after being followed for 1 year . Progressive disease (CNS) was defined as a 25% or greater increase in the sum of the product(s) of the maximal cross-sections on MRI scan, reappearance of any lesion that has disappeared, development of any new lesion(s), stable disease with a deterioration of neurologic exam, or clear worsening of any evaluable disease.
    Time Frame
    assessed every 3 months for 2 years
    Title
    Time to Non-CNS (Systemic) Progression
    Description
    Time to non-CNS progression was calculated from time of protocol entry to time of first systemic progressive disease or death. Patients alive and non-CNS progression-free at last follow-up were censored. Disease progression was defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter (per RECIST criteria). Development of new lesions in non-CNS sites also constituted non-CNS progression. The 21 eligible and treated patients were included in the analysis.
    Time Frame
    assessed every 3 months for 2 years
    Title
    Overall Survival Time
    Description
    Overall survival (months) was calculated from time of protocol entry to time of death from any cause. Patients alive at last follow-up were censored. The 21 eligible and treated patients were included in the analysis.
    Time Frame
    assessed every 3 months for 2 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Histologically confirmed non-small cell lung cancer (NSCLC), including the following histologies: Squamous cell carcinoma Adenocarcinoma Large cell carcinoma Bronchoalveolar carcinoma All variants of NSCLC At least 1 bidimensionally measurable brain metastasis Confirmed by MRI within the past two weeks, and computed tomography (CT) scan is not acceptable Biopsy is not required Not eligible for surgical resection or radiosurgery of brain metastasis Systemic disease not in immediate need of chemotherapy Age>=18 years ECOG Performance status of 0-1 More than 12 weeks of life expectancy Adequate hematologic, renal, and liver function as demonstrated by laboratory values performed within two weeks, inclusive, prior to administration of study drug or registration Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10 g/dL Bilirubin ≤ 2 times upper limit of normal (ULN) Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2 times upper limit of normal (5 times ULN if liver metastases are present) Alkaline phosphatase ≤ 2 times ULN (5 times ULN if liver metastases are present) Creatinine ≤ 1.6 mg/dL Fertile patients must use effective contraception Prior biologic therapy allowed More than 4 weeks since prior chemotherapy Prior radiotherapy for local control or palliative therapy for painful bony lesions allowed Prior surgery for brain metastasis allowed At least 4 weeks since prior radiotherapy to ≥ 15% of bone marrow (2 weeks for < 15% of bone marrow) and recovered No prior radiotherapy to ≥ 50% of bone marrow Concurrent radiotherapy to painful bony lesions allowed provided no more than 15% of bone marrow is irradiated Exclusion Criteria: HIV positive AIDS-related illness Poor medical risks due to active nonmalignant systemic disease Frequent vomiting There is medical condition that would interfere with oral medication intake (e.g., partial bowel obstruction) Pregnant or nursing Prior temozolomide Prior radiotherapy to the brain, including stereotactic radiosurgery to a different lesion Concurrent intensity modulated radiotherapy or 3-D cranial radiotherapy Other concurrent investigational agents Other concurrent treatment for brain metastasis Other concurrent chemotherapy during study radiotherapy Concurrent growth factors to induce elevations in blood counts for the purposes of administration of study drug at scheduled dosing interval or to allow treatment with study drug at a higher dose
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    H. I. Robins, MD, PhD
    Organizational Affiliation
    University of Wisconsin, Madison
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Learn more about this trial

    Temozolomide and Radiation Therapy in Treating Patients With Brain Metastasis Secondary to Non-Small Cell Lung Cancer

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