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

Phase 2

Completed

• Conditions: Metastatic Cancer; Lung Cancer
• Interventions: Drug: Temozolomide; Radiation: Radiation therapy

• Registration Number: NCT00080938
• Lead Sponsor: 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.

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.

Study Timeline

• Study First Submitted: 2004-04-07
• Study First Submitted QC: 2004-04-07
• Study First Posted: 2004-04-08
• Study Start: 2005-12-20
• Primary Completion: 2008-08
• Study Completion: 2009-02
• Results First Submitted: 2010-12-30
• Results First Submitted QC: 2011-08-22
• Results First Posted: 2011-09-27
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-14
• Last Update Posted: 2023-06-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Temozolomide and Radiation	Radiation therapy	Temozolomide:administered orally. Radiation: whole brain radiation therapy
Temozolomide and Radiation	Temozolomide	Temozolomide:administered orally. Radiation: whole brain radiation therapy

Primary Outcome Measures

Name	Time	Method
Number of Patients With Intracranial Response	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

Name	Time	Method
1-year Neurologic (Central Nervous System, CNS) Progression Free Rate	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.
Time to Non-CNS (Systemic) Progression	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.
Overall Survival Time	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.