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

Eastern Cooperative Oncology Group

Status and phase: Completed; Phase 2

Conditions: Metastatic Cancer; Lung Cancer

Treatments: Drug: Temozolomide; Radiation: Radiation therapy

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00080938

E1F03 (Other Identifier)

CDR0000357567

U10CA021115 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 26 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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26 participants in 1 patient group

Temozolomide and Radiation

Experimental group

Description:

Temozolomide:administered orally. Radiation: whole brain radiation therapy

Treatment:

Radiation: Radiation therapy

Drug: Temozolomide