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

• ClinicalTrials.gov Identifier: NCT03391362
• Recruitment Status: Active, not recruiting
• First Posted: January 5, 2018
• Last Update Posted: September 25, 2023
• Sponsor: Dana-Farber Cancer Institute
• Information provided by (Responsible Party): Ayal Aizer, MD, Dana-Farber Cancer Institute

Tracking Information

• First Submitted Date: December 21, 2017
• First Posted Date: January 5, 2018
• Last Update Posted Date: September 25, 2023
• Actual Study Start Date: February 23, 2018
• Estimated Primary Completion Date: February 1, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 29, 2017)

Death due to progressive neurologic disease [ Time Frame: 12 months ]

Clinical parameter to be assessed via review of study visits and medical records indicating cause of death (neurologic versus systemic)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 23, 2018)

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

Original Secondary Outcome Measures (submitted: December 29, 2017)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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

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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Brain Metastases
• Small Cell Lung Cancer

Intervention

Radiation: Stereotactic Radiation

Stereotactic radiation involves using a high dose of radiation that only targets the specific metastases

Study Arms

Experimental: Stereotactic Radiation

• 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

Intervention: Radiation: Stereotactic Radiation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 18, 2019): 100
• Original Estimated Enrollment (submitted: December 29, 2017): 111
• Estimated Study Completion Date: February 1, 2026
• Estimated Primary Completion Date: February 1, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03391362
• Other Study ID Numbers: 17-550
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ayal Aizer, MD, Dana-Farber Cancer Institute
• Original Responsible Party: Ayal Aizer, Dana-Farber Cancer Institute, Principal Investigator
• Current Study Sponsor: Dana-Farber Cancer Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Ayal A Aizer, MD; Brigham and Women's Hospital

• PRS Account: Dana-Farber Cancer Institute
• Verification Date: September 2023