Clinical trial NCT00080938: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-04-08
Enrollment: 26
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 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.

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

Primary outcomes:
measure: Number of Patients With Intracranial Response
timeFrame: assessed every cycle while on treatment, then every 3 months for 2 years
Secondary outcomes:
measure: 1-year Neurologic (Central Nervous System, CNS) Progression Free Rate
timeFrame: assessed every 3 months for 2 years
measure: Time to Non-CNS (Systemic) Progression
timeFrame: assessed every 3 months for 2 years
measure: Overall Survival Time
timeFrame: assessed every 3 months for 2 years
Other outcomes:
Locations:
Study officials:
affiliation: University of Wisconsin, Madison
name: H. I. Robins, MD, PhD
role: STUDY_CHAIR
References: