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

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ClinicalTrials.gov Identifier: NCT00080938
Recruitment Status : Completed
First Posted : April 8, 2004
Results First Posted : September 27, 2011
Last Update Posted : February 15, 2013
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group

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.


Condition or disease Intervention/treatment Phase
Lung Cancer Metastatic Cancer Drug: Temozolomide Radiation: Radiation therapy Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Temozolomide and Radiation Therapy in Patients With Brain Metastasis From Non-small Cell Lung Cancer (NSCLC)
Study Start Date : October 2005
Actual Primary Completion Date : August 2008
Actual Study Completion Date : February 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Temozolomide and Radiation
Temozolomide:administered orally. Radiation: whole brain radiation therapy
Drug: Temozolomide
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.
Other Name: Temodar

Radiation: Radiation therapy
Standard whole brain radiation therapy 30 Gy in ten fractions.
Other Name: Whole brain radiation therapy




Primary Outcome Measures :
  1. Number of Patients With Intracranial Response [ Time Frame: assessed every cycle while on treatment, then every 3 months for 2 years ]
    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. 1-year Neurologic (Central Nervous System, CNS) Progression Free Rate [ Time Frame: assessed every 3 months for 2 years ]
    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.

  2. Time to Non-CNS (Systemic) Progression [ Time Frame: assessed every 3 months for 2 years ]
    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.

  3. Overall Survival Time [ Time Frame: assessed every 3 months for 2 years ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00080938


Sponsors and Collaborators
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Investigators
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Study Chair: H. I. Robins, MD, PhD University of Wisconsin, Madison

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Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00080938     History of Changes
Other Study ID Numbers: CDR0000357567
U10CA021115 ( U.S. NIH Grant/Contract )
E1F03 ( Other Identifier: Eastern Cooperative Oncology Group (ECOG) )
First Posted: April 8, 2004    Key Record Dates
Results First Posted: September 27, 2011
Last Update Posted: February 15, 2013
Last Verified: February 2013

Keywords provided by Eastern Cooperative Oncology Group:
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

Additional relevant MeSH terms:
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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
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents