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

Study Description

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

Condition or disease	Intervention/treatment	Phase
Brain Metastases; Small Cell Lung Cancer	Radiation: Stereotactic Radiation	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Stereotactic Radiation in Patients With Small Cell Lung Cancer and 1-10 Brain Metastases: A Single Arm, Phase II Trial
• Actual Study Start Date: February 23, 2018
• Estimated Primary Completion Date: February 1, 2025
• Estimated Study Completion Date: February 1, 2026

Arms and Interventions

Arm

Intervention/treatment

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

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

Outcome Measures

Primary Outcome Measures :

1. 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)

Secondary Outcome Measures :

1. All-cause mortality [ Time Frame: Until death or loss to follow up, up to 24 months ]
   Clinical parameter
2. 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)
3. Neurocognitive function: Verbal learning and memory [ Time Frame: 12 months ]
   Hopkins Verbal Learning Test -Revised (HVLT-R)
4. Neurocognitive function: Visual attention and task switching [ Time Frame: 12 months ]
   Trail Making Test Part A and B (TMT)
5. Neurocognitive function: Verbal fluency [ Time Frame: 12 months ]
   Controlled Oral Word Association Test (COWAT)
6. Neurocognitive function: Cognitive impairment [ Time Frame: 12 months ]
   Mini Mental Status Examination (MMSE)
7. Ability to complete activities of daily living [ Time Frame: Until death or loss to follow up, up to 24 months ]
   Questionnaire - EQ-5D
8. Performance status [ Time Frame: Until death or loss to follow up, up to 24 months ]
   Karnofsky performance status
9. 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
10. 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
11. 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
12. 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
13. 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
14. 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
15. 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
16. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

Dana-Farber Cancer Institute

Investigators

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

More Information

• Responsible Party: Ayal Aizer, MD, Principal Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT03391362
• Other Study ID Numbers: 17-550
• First Posted: January 5, 2018
• Last Update Posted: September 25, 2023
• Last Verified: September 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Ayal Aizer, MD, Dana-Farber Cancer Institute:

Small Cell Lung Cancer; Brain Metastases; Brain metastasis; Lung cancer; Stereotactic radiation; Stereotactic radiosurgery; SRS; Stereotactic; Radiation; Quality of life; Neurocognitive; Neurocognition

Additional relevant MeSH terms:

Lung Neoplasms; Neoplasm Metastasis; Neoplasms, Second Primary; Small Cell Lung Carcinoma; Brain Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Carcinoma, Bronchogenic; Bronchial Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases