Clinical trial NCT04516070: Stereotactic Radiosurgery for the Treatment of Patients With Small Cell Lung Cancer Brain Metastasis
Official title: Stereotactic Radiosurgery (SRS) as Definitive Management for a Limited Number of Small Cell Lung Cancer (SCLC) Brain Metastasis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Metastatic Lung Small Cell Carcinoma
Metastatic Malignant Neoplasm in the Brain
Stage IV Lung Cancer AJCC v8
Stage IVA Lung Cancer AJCC v8
Stage IVB Lung Cancer AJCC v8
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-08-17
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial investigates how stereotactic radiosurgery affects brain functions while treating patients with small cell lung cancer that has spread to the brain (brain metastasis). Standard of care treatment consists of whole brain radiation therapy, which targets the entire brain, and may result in side effects affecting the nervous system. Stereotactic radiosurgery only targets areas of the brain that are suspected to be affected by the disease. The purpose of this trial is to learn if and how patients' brain functions are affected by the use of stereotactic radiosurgery rather than whole brain radiation therapy in managing brain metastasis caused by small cell lung cancer. Stereotactic radiosurgery may help patients avoid nervous system side effects caused by whole brain radiation therapy.

Detailed description: PRIMARY OBJECTIVE:

I. To estimate the cognitive decline rate at 3 months.

SECONDARY OBJECTIVES:

I. To examine cognitive decline rate on each individual cognitive test at each time point.

II. To examine cognitive decline rates using reliable change index methodology. III. To report the overall survival of patients (death due to any cause) of patients receiving stereotactic radiosurgery (SRS) for small cell lung cancer (SCLC) brain metastasis.

IV. To report rates of local tumor control (of the treated lesions) in the brain post-treatment, as dictated by magnetic resonance imaging (MRI) surveillance schedule above.

V. To report distant tumor control in the brain (of non-treated lesions) post-treatment, as dictated by MRI surveillance schedule above.

VI. To report time elapsed from SRS to whole brain radiation therapy (WBRT). VII. To report rate of intracranial toxicity of SRS in the setting of prior WBRT.

VIII. To report rates of intracranial toxicity of concurrent atezolizumab with SRS.

IX. To determine rates of systemic and intracranial disease control (time to progression) in those who are treated concurrently with atezolizumab and SRS.

X. To determine the rates of SCLC-specific survival. XI. To assess the pre-treatment factors and baseline characteristics in the predictive determination of local control, intracranial control, systemic control, and neurocognitive outcomes.

XII. To assess the correlation between number of lesions and total volume of intracranial disease and neurocognitive outcome.

XIII. To document post-treatment intracranial toxicity profile in patients after SRS.

CORRELATIVE OBJECTIVE:

I. Cerebral spinal fluid (CSF) biomarkers.

OUTLINE:

Patients undergo SRS in the absence of disease progression or unacceptable toxicity. Patients whose disease progresses may be treated with additional courses of SRS per physician discretion.

After completion of study treatment, patients are followed up at 1, 3, 6, 9, 12, 16, 20, 24, 30, and 36 months after SRS.

Eligibility criteria: Inclusion Criteria:

* Patients must have Eastern Cooperative Oncology Group (ECOG) =\< 3
* All patients must have histologic evidence suggesting small cell lung cancer. Histologic confirmation may be from the primary tumor site, or from another metastatic site (systemic lymph node, etc.). Cytology-alone is not an acceptable method of diagnosis.
* Patient has 10 or less brain metastases on contrast-enhanced brain MRI scan obtained no greater than 6 weeks prior to study registration. Biopsy of brain metastasis is not required. A patient may be enrolled with zero brain metastasis assuming that the SRS is to be directed at the post-operative surgical cavity of a resected metastasis.
* Patients must be eligible to have all lesions treated with stereotactic radiosurgery as determined by the study radiation oncologist
* Patients must sign informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of the hospital
* Patients should have normal coagulation \[International Normalized Ratio (INR) \< 1.3\]. within 28 days of enrollment.
* Patient's primary language is English
* No prior radiation therapy to the brain, including WBRT, PCI, or SRS
* Performance Status Assessment
* Standard ECOG performance status assessment will be used and determined by the treating physician

Exclusion Criteria:

* Patients are excluded if they have a history of metastatic cancer in addition to small cell malignancy or a history of uncontrolled non-metastatic cancer. Patients with localized squamous cell carcinoma and/or basal cell carcinoma are not excluded
* Patients are excluded if there is radiographic evidence of leptomeningeal disease
* Patients are excluded if there are malignant cells identified in the CSF on cytologic examination
* Patients are not excluded for circulating tumor deoxyribonucleic acid (DNA) (ctDNA) found in the CSF
* Female patients of childbearing age are excluded if they are pregnant as determined with a urine or serum beta human chorionic gonadotropin (HCG) no greater than 14 days prior to study registration, or breast-feeding
* Patients are excluded if they are unable to obtain an MRI scan for any other reason, including gadolinium allergy
* Patients are excluded with medical history of a psychiatric or neurologic illness, or other comorbidities believed to affect cognitive function. Subjects with neurocognitive deficit related to brain metastasis are an exception to this criterion and may qualify for the study.

Primary outcomes:
measure: Cognitive decline
timeFrame: At 3 months post-stereotactic radiosurgery (SRS)
measure: Incidence of adverse events
timeFrame: Up to 36 months
Secondary outcomes:
measure: Cognitive decline
timeFrame: Up to 36 months
measure: Change in neurocognitive score
timeFrame: Baseline, up to 36 months
measure: Overall survival
timeFrame: Time from SRS until death or last follow-up, assessed up to 36 months
measure: Small cell lung cancer (SCLC)-specific survival
timeFrame: Time from SRS till SCLC-related death or last follow-up, assessed up to 36 months
measure: Time to neurocognitive decline
timeFrame: Time from date of SRS till the cognitive decline, assessed up to 36 months
measure: Time duration from SRS to whole brain radiation therapy (WBRT)
timeFrame: Time from SRS to the start of WBRT treatment, assessed up to 36 months
measure: Local tumor control rates
timeFrame: Up to 36 months
measure: Distant tumor control rate
timeFrame: Up to 36 months
measure: Rate of systemic and intracranial disease control rate
timeFrame: Up to 36 months
measure: Response to SRS therapy
timeFrame: Up to 36 months
measure: Post-treatment intracranial toxicity profile
timeFrame: Up to 36 months
measure: Rate of intracranial toxicity of SRS in the setting of prior WBRT
timeFrame: Up to 36 months
measure: Rate of intracranial toxicity concurrent atezolizumab with SRS
timeFrame: Up to 36 months
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Jing Li
role: PRINCIPAL_INVESTIGATOR
References: