Pre-operative SRS or Post-operative SRS in Treating Cancer Patients With Brain Metastases

Phase 3

Recruiting

• Conditions: Malignant Neoplasm; Metastatic Malignant Neoplasm in the Brain
• Interventions: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Stereotactic Radiosurgery

• Registration Number: NCT03741673
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

This phase III trial studies stereotactic radiosurgery (SRS) before surgery to see how well it works compared with SRS after surgery in treating patients with cancer that has spread to the brain (brain metastases). SRS is the delivery of focused, high-dose radiation given in a single session to the tumors, with a minimal dose given to uninvolved areas of the brain.

Detailed Description

PRIMARY OBJECTIVE:

I. To investigate the 1 year leptomeningeal disease (LMD)-free rate among patients with surgically resectable metastatic brain lesions randomized to post-operative stereotactic radiosurgery (SRS) (standard care) versus pre-operative SRS followed by surgery (experimental arm).

SECONDARY OBJECTIVE:

I. To investigate the local control (LC), distant brain metastasis rate, overall survival (OS) of pre-operative (pre-op) versus (vs) post-operative (post-op) SRS in patients with brain metastasis.

EXPLORATORY OBJECTIVES:

I. To assess the reliability of different imaging features by using a combination of patient data and phantom data to quantify the uncertainties associated with using magnetic resonance imaging (MRI) for radiomics studies.

II. To assess the correlation of imaging-pathology correlates using multiparametric imaging that characterize the tumor and peri-tumoral microenvironment including features such as tumor vascular characteristics, cellular density, oxygenation and presence of inflammation/immune reactivity.

III. To investigate the neuro-cognitive impact, patient reported outcomes and health-related quality of life of pre-operative (pre-op) vs post-operative (post-op) SRS in patients with brain metastasis.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I (PRE-OPERATIVE SRS): Patients undergo SRS within 15 days of randomization followed by surgery within 15 days. Patients may undergo additional SRS if disease returns after treatment.

GROUP II (POST-OPERATIVE SRS): Patients undergo surgery within 15 days of randomization followed by standard of care SRS within 30 days. Patients may undergo additional SRS if disease returns after treatment.

After completion of study treatment, patients are followed up periodically.

Study Timeline

• Study Start: 2018-11-08
• Study First Submitted: 2018-11-09
• Study First Submitted QC: 2018-11-14
• Study First Posted: 2018-11-15
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-11
• Last Update Posted: 2025-03-13
• Primary Completion: 2027-01-31
• Study Completion: 2027-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

• The primary lesion pre-operatively can have a maximum diameter of =< 4 cm for single fraction and =< 7 cm for multifraction therapy
• Patients must be considered candidates for SRS within +/- 30 days of surgical resection as defined by either history and physical (H&P) or presentation at brain metastasis tumor board conference note
• Patients must have a Karnofsky performance scores >= 70 or Eastern Cooperative Oncology Group (ECOG) >= 2 within 30 days of enrollment
• Patients must agree to randomization as documented by signing the Institutional Review Board (IRB) approved consent form
• No radiographic evidence of leptomeningeal disease on MD Anderson Cancer Center (MDACC) departmental radiology report or study neuro-radiologist review
• Documented history of malignancy

Exclusion Criteria

• Patients who have received prior radiation therapy to the brain for any reason
• The primary tumor is small-cell lung cancer, lymphoma, leukemia, or multiple myeloma
• For females, if they are pregnant or breast-feeding (The exclusion is made because gadolinium may be teratogenic in pregnancy)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group I (pre-operative SRS)	Stereotactic Radiosurgery	Patients undergo SRS within 30 days of randomization followed by surgery within 30 days. Patients may undergo additional SRS if disease returns after treatment.
Group II (post-operative SRS)	Quality-of-Life Assessment	Patients undergo surgery within 30 days of randomization followed by standard of care SRS within 30 days. Patients may undergo additional SRS if disease returns after treatment.
Group II (post-operative SRS)	Questionnaire Administration	Patients undergo surgery within 30 days of randomization followed by standard of care SRS within 30 days. Patients may undergo additional SRS if disease returns after treatment.
Group I (pre-operative SRS)	Quality-of-Life Assessment	Patients undergo SRS within 30 days of randomization followed by surgery within 30 days. Patients may undergo additional SRS if disease returns after treatment.
Group II (post-operative SRS)	Stereotactic Radiosurgery	Patients undergo surgery within 30 days of randomization followed by standard of care SRS within 30 days. Patients may undergo additional SRS if disease returns after treatment.
Group I (pre-operative SRS)	Questionnaire Administration	Patients undergo SRS within 30 days of randomization followed by surgery within 30 days. Patients may undergo additional SRS if disease returns after treatment.

Primary Outcome Measures

Name	Time	Method
Leptomeningeal disease (LMD)-free rate	At 1 year	Aalen-Johansen estimates will be used for LMD. Uni- and multi-variable analysis of time to LMD will be done using Fine-Gray proportional hazards regression. Model assumptions will be verified graphically by residual analyses.

Secondary Outcome Measures

Name	Time	Method
Distant brain control	At 1 year	Aalen-Johansen estimates will be used for distant brain recurrence. Uni- and multi-variable analysis of time to distant brain recurrence will be done using Fine-Gray proportional hazards regression. Model assumptions will be verified graphically by residual analyses.
Local control rate	At 1 year	Aalen-Johansen estimates will be used for local recurrence. Uni- and multi-variable analysis of time to local recurrence will be done using Fine-Gray proportional hazards regression. Model assumptions will be verified graphically by residual analyses.
Overall survival (OS)	At 1 year	Kaplan-Meier estimates will be utilized for survival. Uni- and multi-variable analysis of overall survival will be done with Cox proportional hazards regression.

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States