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Stereotactic Radiosurgery for the Treatment of Patients With Small Cell Lung Cancer Brain Metastasis

Primary Purpose

Metastatic Lung Small Cell Carcinoma, Metastatic Malignant Neoplasm in the Brain, Stage IV Lung Cancer AJCC v8

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Questionnaire Administration
Stereotactic Radiosurgery
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Lung Small Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 5 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 postoperative 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) and be able to withhold anticoagulation/antiplatelet medications a minimum of 24 hours prior to radiosurgery treatment (or until INR normalizes), on the day of treatment and 24 hours after radiosurgery treatment has concluded
  • Patient's primary language is English
  • 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

Sites / Locations

  • M D Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (SRS)

Arm Description

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.

Outcomes

Primary Outcome Measures

Cognitive decline
Will be defined as a decline of >= 1 standard deviation from baseline on at least 1 of the 5 cognitive tests. Will be estimated along with the 95% confidence interval. For patients with or without prior radiation therapy to the central nervous system, the cognitive decline rate will also be estimated respectively. Fisher exact test will be used to compare the neurocognitive decline rate at 3 month post-SRS in subgroups (e.g. prior therapy difference).
Incidence of adverse events
All toxicities will be assessed with National Cancer Institute predefined Common Terminology Criteria for Adverse Events version 5.

Secondary Outcome Measures

Cognitive decline
Will use descriptive statistics and boxplots to summarize and illustrate the neurocognitive function score at each assessment time.
Change in neurocognitive score
Will summarize and illustrate the change from baseline in neurocognitive score. Will also model the cognitive data with mixed effects regression including baseline neurocognitive scores, time, and number of lesions, extra-cranial disease, and a patient specific random effect.
Overall survival
Will be estimated using the product-limit estimator of Kaplan and Meier, and log-rank test will be used for comparison of neurocognitive decline rate in subgroups (e.g. prior radiation treatment status). Cox proportional hazards regression will be used to model time to event survival as a function of age, performance status, extra-cranial disease, and other factors.
Small cell lung cancer (SCLC)-specific survival
Will be estimated using the product-limit estimator of Kaplan and Meier, and log-rank test will be used for comparison of neurocognitive decline rate in subgroups (e.g. prior radiation treatment status). Cox proportional hazards regression will be used to model time to event survival as a function of age, performance status, extra-cranial disease, and other factors.
Time to neurocognitive decline
Will be estimated using the product-limit estimator of Kaplan and Meier, and log-rank test will be used for comparison of neurocognitive decline rate in subgroups (e.g. prior radiation treatment status). Cox proportional hazards regression will be used to model time to event survival as a function of age, performance status, extra-cranial disease, and other factors.
Time duration from SRS to whole brain radiation therapy (WBRT)
Will be estimated using the product-limit estimator of Kaplan and Meier, and log-rank test will be used for comparison of neurocognitive decline rate in subgroups (e.g. prior radiation treatment status). Cox proportional hazards regression will be used to model time to event survival as a function of age, performance status, extra-cranial disease, and other factors.
Local tumor control rates
Will be estimated along with 95% confidence intervals. The association between the control rate and patient characteristics including pre-treatment factors (e.g. number of lesions) will be evaluated using Wilcoxon rank sum test or Fisher exact test. Logistic regression will be used to assess different patient clinical factor effect on the control rate.
Distant tumor control rate
Will be estimated along with 95% confidence intervals. The association between the control rate and patient characteristics including pre-treatment factors (e.g. number of lesions) will be evaluated using Wilcoxon rank sum test or Fisher exact test. Logistic regression will be used to assess different patient clinical factor effect on the control rate.
Rate of systemic and intracranial disease control rate
Will be estimated along with 95% confidence intervals. The association between the control rate and patient characteristics including pre-treatment factors (e.g. number of lesions) will be evaluated using Wilcoxon rank sum test or Fisher exact test. Logistic regression will be used to assess different patient clinical factor effect on the control rate.
Response to SRS therapy
Will be determined by the radiology report. Will be estimated along with 95% confidence intervals. The association between the control rate and patient characteristics including pre-treatment factors (e.g. number of lesions) will be evaluated using Wilcoxon rank sum test or Fisher exact test. Logistic regression will be used to assess different patient clinical factor effect on the control rate.
Post-treatment intracranial toxicity profile
Will be summarized and documented.
Rate of intracranial toxicity of SRS in the setting of prior WBRT
Will be summarized according to intensity and treatment relationship, and categorized by System Organ Class.
Rate of intracranial toxicity concurrent atezolizumab with SRS
Will be summarized according to intensity and treatment relationship, and categorized by System Organ Class.

Full Information

First Posted
August 13, 2020
Last Updated
September 14, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04516070
Brief Title
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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 28, 2020 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (SRS)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Intervention Type
Radiation
Intervention Name(s)
Stereotactic Radiosurgery
Other Intervention Name(s)
Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, Stereotactic Radiation Therapy, Stereotactic Radiotherapy, stereotaxic radiation therapy, stereotaxic radiosurgery
Intervention Description
Undergo SRS
Primary Outcome Measure Information:
Title
Cognitive decline
Description
Will be defined as a decline of >= 1 standard deviation from baseline on at least 1 of the 5 cognitive tests. Will be estimated along with the 95% confidence interval. For patients with or without prior radiation therapy to the central nervous system, the cognitive decline rate will also be estimated respectively. Fisher exact test will be used to compare the neurocognitive decline rate at 3 month post-SRS in subgroups (e.g. prior therapy difference).
Time Frame
At 3 months post-stereotactic radiosurgery (SRS)
Title
Incidence of adverse events
Description
All toxicities will be assessed with National Cancer Institute predefined Common Terminology Criteria for Adverse Events version 5.
Time Frame
Up to 36 months
Secondary Outcome Measure Information:
Title
Cognitive decline
Description
Will use descriptive statistics and boxplots to summarize and illustrate the neurocognitive function score at each assessment time.
Time Frame
Up to 36 months
Title
Change in neurocognitive score
Description
Will summarize and illustrate the change from baseline in neurocognitive score. Will also model the cognitive data with mixed effects regression including baseline neurocognitive scores, time, and number of lesions, extra-cranial disease, and a patient specific random effect.
Time Frame
Baseline, up to 36 months
Title
Overall survival
Description
Will be estimated using the product-limit estimator of Kaplan and Meier, and log-rank test will be used for comparison of neurocognitive decline rate in subgroups (e.g. prior radiation treatment status). Cox proportional hazards regression will be used to model time to event survival as a function of age, performance status, extra-cranial disease, and other factors.
Time Frame
Time from SRS until death or last follow-up, assessed up to 36 months
Title
Small cell lung cancer (SCLC)-specific survival
Description
Will be estimated using the product-limit estimator of Kaplan and Meier, and log-rank test will be used for comparison of neurocognitive decline rate in subgroups (e.g. prior radiation treatment status). Cox proportional hazards regression will be used to model time to event survival as a function of age, performance status, extra-cranial disease, and other factors.
Time Frame
Time from SRS till SCLC-related death or last follow-up, assessed up to 36 months
Title
Time to neurocognitive decline
Description
Will be estimated using the product-limit estimator of Kaplan and Meier, and log-rank test will be used for comparison of neurocognitive decline rate in subgroups (e.g. prior radiation treatment status). Cox proportional hazards regression will be used to model time to event survival as a function of age, performance status, extra-cranial disease, and other factors.
Time Frame
Time from date of SRS till the cognitive decline, assessed up to 36 months
Title
Time duration from SRS to whole brain radiation therapy (WBRT)
Description
Will be estimated using the product-limit estimator of Kaplan and Meier, and log-rank test will be used for comparison of neurocognitive decline rate in subgroups (e.g. prior radiation treatment status). Cox proportional hazards regression will be used to model time to event survival as a function of age, performance status, extra-cranial disease, and other factors.
Time Frame
Time from SRS to the start of WBRT treatment, assessed up to 36 months
Title
Local tumor control rates
Description
Will be estimated along with 95% confidence intervals. The association between the control rate and patient characteristics including pre-treatment factors (e.g. number of lesions) will be evaluated using Wilcoxon rank sum test or Fisher exact test. Logistic regression will be used to assess different patient clinical factor effect on the control rate.
Time Frame
Up to 36 months
Title
Distant tumor control rate
Description
Will be estimated along with 95% confidence intervals. The association between the control rate and patient characteristics including pre-treatment factors (e.g. number of lesions) will be evaluated using Wilcoxon rank sum test or Fisher exact test. Logistic regression will be used to assess different patient clinical factor effect on the control rate.
Time Frame
Up to 36 months
Title
Rate of systemic and intracranial disease control rate
Description
Will be estimated along with 95% confidence intervals. The association between the control rate and patient characteristics including pre-treatment factors (e.g. number of lesions) will be evaluated using Wilcoxon rank sum test or Fisher exact test. Logistic regression will be used to assess different patient clinical factor effect on the control rate.
Time Frame
Up to 36 months
Title
Response to SRS therapy
Description
Will be determined by the radiology report. Will be estimated along with 95% confidence intervals. The association between the control rate and patient characteristics including pre-treatment factors (e.g. number of lesions) will be evaluated using Wilcoxon rank sum test or Fisher exact test. Logistic regression will be used to assess different patient clinical factor effect on the control rate.
Time Frame
Up to 36 months
Title
Post-treatment intracranial toxicity profile
Description
Will be summarized and documented.
Time Frame
Up to 36 months
Title
Rate of intracranial toxicity of SRS in the setting of prior WBRT
Description
Will be summarized according to intensity and treatment relationship, and categorized by System Organ Class.
Time Frame
Up to 36 months
Title
Rate of intracranial toxicity concurrent atezolizumab with SRS
Description
Will be summarized according to intensity and treatment relationship, and categorized by System Organ Class.
Time Frame
Up to 36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 5 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 postoperative 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) and be able to withhold anticoagulation/antiplatelet medications a minimum of 24 hours prior to radiosurgery treatment (or until INR normalizes), on the day of treatment and 24 hours after radiosurgery treatment has concluded Patient's primary language is English 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jing Li
Phone
713-563-2300
Email
jing.li@mdanderson.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jing Li
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jing Li
Phone
713-563-2300
First Name & Middle Initial & Last Name & Degree
Jing Li

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center

Learn more about this trial

Stereotactic Radiosurgery for the Treatment of Patients With Small Cell Lung Cancer Brain Metastasis

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