Lung Cancer
Conditions
Keywords
limited stage small cell lung cancer
Brief summary
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which radiation therapy regimen is more effective in preventing brain metastases in patients with limited-stage small cell lung cancer while taking into account chronic neurotoxicity from radiation therapy. PURPOSE: This randomized phase II trial compares the incidence of chronic neurotoxicity between three different brain irradiation regimens. The corresponding phase III component addressing the prevention of brain metastases was run by EORTC and reported separately (NCT00005062).
Detailed description
OBJECTIVES: * Compare the incidence of chronic neurotoxicity in patients treated with these regimens. * Compare quality of life of patients treated with these regimens. (phase III closed to accrual as of 12/31/05) OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (60 and under vs over 60) and time since induction therapy (90 days or less vs 91-180 days vs 181-240 days). Patients are randomized to 1 of 3 treatment arms. * Arm I: Patients undergo prophylactic cranial irradiation (PCI) once daily 5 days a week. Treatment continues for 2 weeks in the absence of unacceptable toxicity. * Arm II: Patients undergo PCI once daily 5 days a week. Treatment continues for 2.6 weeks in the absence of unacceptable toxicity. * Arm III: Patients undergo PCI twice daily 5 days a week. Treatment continues for 3.4 weeks in the absence of unacceptable toxicity. Quality of life is assessed at baseline, every 6 months for 1 year, and then annually for 3 years. Patients are followed every 6 months for 1 year and then annually for 3 years. PROJECTED ACCRUAL: A total of 264 patients will be accrued for this study within 3.5 years.
Interventions
RADIATIONProphylactic cranial irradiation, 2.5 Gy fx
Prophylactic cranial irradiation, 2.5 Gy once daily, M-F, in 10 fractions (fx) for a total of 25 Gy
RADIATIONProphylactic cranial irradiation, 2.0 Gy fx
Prophylactic cranial irradiation, 2.0 Gy once daily, M-F, in 18 fractions (fx) for a total of 36 Gy
RADIATIONProphylactic cranial irradiation, 1.5 Gy fx
Prophylactic cranial irradiation, 1.5 Gy twice daily, M-F, in 24 fractions (fx) for a total dose of 36 Gy
Sponsors
National Cancer Institute (NCI)
Radiation Therapy Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed small cell lung cancer by fine needle aspiration, biopsy, or 2 positive sputa * Limited stage (I-IIIB) * Confined to 1 hemithorax * No T4 based on malignant pleural effusion, or N3 disease based on contralateral hilar or contralateral supraclavicular involvement * Complete response after induction chemotherapy (with or without thoracic radiotherapy) * Consolidative chest radiotherapy may be initiated before study * No radiographic evidence of any of the following: * Brain metastases * Normal brain CT scan or MRI less than 1 month before study * Ipsilateral lung metastases * Malignant pleural effusion * Minimal pleural effusion by chest CT scan allowed, but not by chest x-ray PATIENT CHARACTERISTICS: Age * Not specified Performance status * Zubrod 0-1 Life expectancy * Not specified Hematopoietic * Absolute granulocyte count at least 1,500/mm\^3 * Platelet count at least 75,000/mm\^3 * Hemoglobin at least 10.0 g/dL\^ Hepatic * Not specified Renal * Not specified Pulmonary * See Disease Characteristics Other * Not pregnant or nursing * Fertile patients must use effective contraception * Neurological function class 1 or 2 * No epilepsy requiring permanent oral medication * No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix * No other serious medical or psychiatric condition that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * See Disease Characteristics * At least 1 week since prior chemotherapy * No concurrent chemotherapy Endocrine therapy * Not specified Radiotherapy * See Disease Characteristics * No prior external beam radiotherapy to the head or neck, including stereotactic radiotherapy * Concurrent thoracic radiotherapy allowed Surgery * Not specified Other * No concurrent antitumor agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Chronic Neurotoxicity | From study registration to one year. | Chronic neurotoxicity is defined as a drop in one standard error of measurement (SEM) in any one of the three tests comprising the neuropsychological test battery (Hopkins Verbal Learning Test, Controlled Word Association Test, and Trail-Making Test) without development of brain metastasis by one year. The SEM is calculated as the standard deviation of the baseline test multiplied by the square root of one minus the published reliability coefficient for the test. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I Prophylactic cranial irradiation, 2.5 Gy FX: Prophylactic cranial irradiation, 2.5 Gy once daily, M-F, in 10 fractions for a total of 25 Gy | 131 |
| Arm II Prophylactic cranial irradiation, 2.0 Gy FX: Prophylactic cranial irradiation, 2.0 Gy once daily, M-F, in 18 fractions for a total of 36 Gy | 67 |
| Arm III Prophylactic cranial irradiation, 1.5 Gy FX: Prophylactic cranial irradiation, 1.5 Gy twice daily, M-F, in 24 fractions for a total dose of 36 Gy | 66 |
| Total | 264 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Arm I | Arm II | Arm III | Total |
|---|---|---|---|---|
| Age, Continuous | 62 years | 62 years | 61 years | 62 years |
| Sex: Female, Male Female | 53 Participants | 33 Participants | 32 Participants | 118 Participants |
| Sex: Female, Male Male | 78 Participants | 34 Participants | 34 Participants | 146 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 54 / 128 | 37 / 66 | 26 / 64 |
| serious Total, serious adverse events | 6 / 128 | 2 / 66 | 4 / 64 |
Outcome results
Primary
Incidence of Chronic Neurotoxicity
Chronic neurotoxicity is defined as a drop in one standard error of measurement (SEM) in any one of the three tests comprising the neuropsychological test battery (Hopkins Verbal Learning Test, Controlled Word Association Test, and Trail-Making Test) without development of brain metastasis by one year. The SEM is calculated as the standard deviation of the baseline test multiplied by the square root of one minus the published reliability coefficient for the test.
Time frame: From study registration to one year.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I | Incidence of Chronic Neurotoxicity | 60 percentage of participants |
| Arm II | Incidence of Chronic Neurotoxicity | 85 percentage of participants |
| Arm III | Incidence of Chronic Neurotoxicity | 89 percentage of participants |