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

Sponsor:	Eastern Cooperative Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by (Responsible Party):	Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:	NCT00080938

Purpose

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	Intervention	Phase
Lung Cancer Metastatic Cancer	Drug: Temozolomide Radiation: Radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: 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)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Temozolomide

U.S. FDA Resources

Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:

Number of Patients With Intracranial Response [ Time Frame: assessed every cycle while on treatment, then every 3 months for 2 years ] [ Designated as safety issue: No ]
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-year Neurologic (Central Nervous System, CNS) Progression Free Rate [ Time Frame: assessed every 3 months for 2 years ] [ Designated as safety issue: No ]
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 [ Time Frame: assessed every 3 months for 2 years ] [ Designated as safety issue: No ]
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 [ Time Frame: assessed every 3 months for 2 years ] [ Designated as safety issue: No ]
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.

Enrollment:	26
Study Start Date:	October 2005
Study Completion Date:	February 2009
Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Arms

Assigned Interventions

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

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00080938

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

H. I. Robins, MD, PhD

University of Wisconsin, Madison

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:	NCT00080938 History of Changes
Other Study ID Numbers:	CDR0000357567, U10CA021115, E1F03
Study First Received:	April 7, 2004
Results First Received:	December 30, 2010
Last Updated:	August 22, 2011
Health Authority:	United States: Federal Government

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:

Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases

Respiratory Tract Diseases
Neoplastic Processes
Pathologic Processes
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 12, 2012