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

A Phase III Trial of Pre-Operative Stereotactic Radiosurgery (SRS) Versus Post-Operative SRS for Brain Metastases

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.

Study Overview

• Status: Recruiting
• Conditions: Malignant Neoplasm; Metastatic Malignant Neoplasm in the Brain
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Stereotactic Radiosurgery

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 Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Debra Yeboa; Phone Number: 713-563-2300; Email: dnyeboa@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • M D Anderson Cancer Center
      • Contact: Debra N. Yeboa; Phone Number: 713-563-2300
      • Principal Investigator: Debra N. Yeboa

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group I (pre-operative SRS); Patients undergo SRS within 30 days of randomization followed by surgery within 30 days. Patients may undergo additional SRS if disease returns after treatment.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Radiation: Stereotactic Radiosurgery; Undergo SRS; Other Names: Stereotactic External Beam Irradiation; stereotactic external-beam radiation therapy; stereotactic radiation therapy; Stereotactic Radiotherapy; stereotaxic radiation therapy; stereotaxic radiosurgery
Active Comparator: Group II (post-operative SRS); 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.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Radiation: Stereotactic Radiosurgery; Undergo SRS; Other Names: Stereotactic External Beam Irradiation; stereotactic external-beam radiation therapy; stereotactic radiation therapy; Stereotactic Radiotherapy; stereotaxic radiation therapy; stereotaxic radiosurgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Leptomeningeal disease (LMD)-free rate	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.	At 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local control rate	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.	At 1 year
Distant brain control	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.	At 1 year
Overall survival (OS)	Kaplan-Meier estimates will be utilized for survival. Uni- and multi-variable analysis of overall survival will be done with Cox proportional hazards regression.	At 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delta radiomics	Radiomic texture features and changes in features at diagnosis with pathology and over time will be included in various classifiers for modeling including decision trees, discriminate analysis, and nearest neighbor classifiers using classification learner in Matlab.	Up to 4 years
Circulating tumor cell analysis		Up to 4 years
Cerebral spinal fluid analysis		Up to 4 years
Neurocognitive function measured by HVLT-R questionnaire	Measured by neurocognitive decline on Hopkins Verbal Learning Test-Revised (HVLT-R)	Up to 1 year from start of treatment
Symptom burden questionnaire	Measured by the MD Anderson Symptom Inventory Brain Tumor (MDASI-BT).	Up to 1 year from start of treatment
Health outcomes questionnaire	Measured by the European Quality of Life Five Dimension Five Level Scale questionnaire (EQ-5D-5L).	Up to 1 year from start of treatment
Neurocognitive function measured by COWA questionnaire	Measured by neurocognitive decline on Controlled Oral Word Association (COWA)	Up to 1 year from start of treatment
Neurocognitive function measured by TMT questionnaire	Measured by neurocognitive decline on and Trail Making Test (TMT) parts A and B	Up to 1 year from start of treatment
Neurocognitive function measured by CTB COMP questionnaire	Measured by neurocognitive decline on Clinical Trial Battery Composite (CTB COMP) score.	Up to 1 year from start of treatment

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Debra N Yeboa, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2018
• Primary Completion (Estimated): July 10, 2024
• Study Completion (Estimated): July 10, 2024

Study Registration Dates

• First Submitted: November 9, 2018
• First Submitted That Met QC Criteria: November 14, 2018
• First Posted (Actual): November 15, 2018

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms; Brain Neoplasms
• Other Study ID Numbers: 2018-0552 (Other Identifier: M D Anderson Cancer Center); NCI-2018-02220 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No