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

NCT ID: NCT00080938

Last Updated: 2023-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-20
• Study Completion Date: 2009-02-28

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.

Conditions

Lung Cancer; Metastatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Temozolomide and Radiation

Temozolomide:administered orally. Radiation: whole brain radiation therapy

Group Type: EXPERIMENTAL

Temozolomide

Intervention Type: DRUG

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.

Radiation therapy

Intervention Type: RADIATION

Standard whole brain radiation therapy 30 Gy in ten fractions.

Interventions

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.

Intervention Type: DRUG

Radiation therapy

Standard whole brain radiation therapy 30 Gy in ten fractions.

Intervention Type: RADIATION

Other Intervention Names

Temodar; Whole brain radiation therapy

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

H. I. Robins, MD, PhD

Role: STUDY_CHAIR

University of Wisconsin, Madison

Other Identifiers

U10CA021115

Identifier Type: NIH

Identifier Source: secondary_id

View Link

E1F03

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000357567

Identifier Type: -

Identifier Source: org_study_id