Stereotactic Radiation in Patients With Small Cell Lung Cancer and 1-10 Brain Metastases

Study Overview
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Brief Summary
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This research study is studying stereotactic radiation (focused/pinpoint radiation that targets each individual tumor but not the surrounding brain) instead of whole-brain radiation (radiation targeting the entire brain) as a possible treatment for patients with small cell lung cancer and 1-10 brain metastases. The intervention involved in this study is: -Stereotactic (focused, pinpoint) radiation

Detailed Description
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This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational treatment, in this case stereotactic radiation, to learn whether this treatment works in treating a specific disease. Investigational means that the treatment is being studied. In patients with a limited number of brain metastases (spread of a cancer that started outside of the brain to the brain itself) the standard radiation option is stereotactic radiation, which involves using a high dose of radiation that only targets the specific metastases that are visible on imaging of the brain, not the whole brain itself. However, studies evaluating the role of stereotactic radiation to treat brain metastases generally excluded patients with small cell lung cancer. Therefore, among patients with small cell lung cancer and brain metastases, the typical treatment that has been offered is whole brain radiation. However, whole brain radiation has deleterious associated side effects including significant fatigue and permanent memory/attention problems. The investigators are studying whether stereotactic radiation can be effectively utilized for patients with small cell lung cancer and brain metastases in order to avoid such side effects.

Official Title
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Stereotactic Radiation in Patients With Small Cell Lung Cancer and 1-10 Brain Metastases: A Single Arm, Phase II Trial

Conditions
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Brain Metastases, Small Cell Lung Cancer

Intervention / Treatment
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* Radiation: Stereotactic Radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have a biopsy-proven tumor consistent with small cell lung cancer and intracranial lesions radiographically consistent with or pathologically proven to be brain metastases. Patients who have undergone prior systemic therapy are eligible. Patients who have undergone resection of one or more brain metastases but who have not yet started adjuvant radiotherapy are eligible for the study. 1-10 definitive intracranial lesions must be present on MRI of the brain. Age >=18 years at diagnosis of brain metastases. Exclusion Criteria: Participants who have undergone prior radiation for brain metastases. Participants who have received prophylactic cranial radiation for prevention of brain metastases Participants who cannot receive gadolinium Participants with stage IV-V chronic kidney disease or end stage renal disease Participants with widespread, definitive leptomeningeal disease Participants with a maximum tumor diameter exceeding 5 cm (if not resected) Participants with >6 definitive lesions consistent with brain metastases Participants with inadequate mental capacity to complete quality of life questionnaires

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stereotactic Radiation<br>Stereotactic radiation will begin within 14 days of the MRI used for radiation planning Lesions <2 cm in maximum diameter will be treated with stereotactic radiosurgery, generally 20 Gy in 1 fraction Lesions between 2.0 and 3.0 cm in maximum diameter will generally be treated to 18 Gy in 1 fraction Lesions >3 cm will be generally be treated with stereotactic radiotherapy to 30 Gy in 5 fractions | Radiation: Stereotactic Radiation<br>* Stereotactic radiation involves using a high dose of radiation that only targets the specific metastases<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death due to progressive neurologic disease | Clinical parameter to be assessed via review of study visits and medical records indicating cause of death (neurologic versus systemic) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | Clinical parameter | Until death or loss to follow up, up to 24 months | 
| Quality of life as assessed by patient Questionnaire | Questionnaire - MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) | Until death or loss to follow up, up to 24 months | 
| Neurocognitive function: Verbal learning and memory | Hopkins Verbal Learning Test -Revised (HVLT-R) | 12 months | 
| Neurocognitive function: Visual attention and task switching | Trail Making Test Part A and B (TMT) | 12 months | 
| Neurocognitive function: Verbal fluency | Controlled Oral Word Association Test (COWAT) | 12 months | 
| Neurocognitive function: Cognitive impairment | Mini Mental Status Examination (MMSE) | 12 months | 
| Ability to complete activities of daily living | Questionnaire - EQ-5D | Until death or loss to follow up, up to 24 months | 
| Performance status | Karnofsky performance status | Until death or loss to follow up, up to 24 months | 
| Incidence and time to detection of new brain metastases | Radiographic assessment of first appearance of new brain metastases | Until death or loss to follow up, up to 24 months | 
| Incidence and time to local recurrence of existing brain metastases | Radiographic assessment of first local recurrence in the 1-6 brain metastases that were initially treated with radiation | Until death or loss to follow up, up to 24 months | 
| Incidence and time to development of radiation necrosis | Radiographic assessment of first appearance of radiation necrosis | Until death or loss to follow up, up to 24 months | 
| Incidence and time to development of leptomeningeal disease | Radiographic assessment of first appearance of leptomeningeal disease | Until death or loss to follow up, up to 24 months | 
| Incidence and time to progressive intracranial disease | Radiographic assessment of first appearance of progressive intracranial disease | Until death or loss to follow up, up to 24 months | 
| Incidence and time to salvage craniotomy | Clinical assessment of first use of neurosurgical resection as salvage therapy | Until death or loss to follow up, up to 24 months | 
| Incidence and time to additional CNS-directed radiotherapeutic treatments (stereotactic or WBRT) after the initial course | Clinical assessment of first use of salvage brain-directed radiation | Until death or loss to follow up, up to 24 months | 
| Incidence and time to the development of seizures | Clinical assessment of first post-treatment seizure as assessed during routine study visits and via medical record review | Until death or loss to follow up, up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Small Cell Lung Cancer, Brain Metastases, Brain metastasis, Lung cancer, Stereotactic radiation, Stereotactic radiosurgery, SRS, Stereotactic, Radiation, Quality of life, Neurocognitive, Neurocognition