Pre-Operative or Post-Operative Stereotactic Radiosurgery in Treating Patients With Operative Metastatic Brain Tumors

Malignant Solid Neoplasm Clinical Trial

Official title:

Pre-Operative vs. Post-Operative Stereotactic Radiosurgery for Operative Metastatic Brain Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03750227
• Other study ID #: MC167C
• Secondary ID: NCI-2018-0279917
• Status: Recruiting
• Phase: Phase 3
• Start date: November 19, 2018
• Est. completion date: November 8, 2025

Study information

• Verified date: June 2024
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase III trial studies the side effects and how well stereotactic radiosurgery (SRS) works before or after surgery in patients with tumors that has spread to the brain or that can be removed by surgery. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue.

Description:

PRIMARY OBJECTIVE:

I. To determine for patients with brain metastases meeting the inclusion criteria, whether there is an increase in the time to a composite endpoint of adverse outcomes including the first occurrence of either: local recurrence, leptomeningeal disease, or symptomatic radiation brain necrosis in patients who receive SRS prior to surgery as compared to patients who receive surgery prior to SRS.

SECONDARY OBJECTIVES:

I. To determine for patients with brain metastases whether there is improved overall survival for patients who receive SRS prior to surgery as compared to patients who receive SRS after surgery.

II. To determine for patients with brain metastases whether there are improved patient reported outcomes including quality of life for patients who receive SRS prior to surgery as compared to patients who receive SRS after surgery.

III. To determine if preoperative SRS increases rates of surgical morbidity including postoperative complications such as wound infection, need for longer hospital stays, or readmission compared to a surgery first approach for resectable brain metastases.

IV. To determine for patients with brain metastases whether there is a higher rate of completion of planned therapies for patients who receive SRS prior to surgery as compared to patients who receive surgery prior to SRS.

V. To determine for patients with brain metastases whether there is a shorter time to initiation or re-initiation of systemic therapy with pre-operative versus post-operative SRS.

VI. To determine for patients treated with pre-operative SRS whether there is a longer interval to regional progression, any central nervous system (CNS) progression or need for subsequent intracranial treatment compared to patients receiving post-operative SRS.

VII. To determine for patients with pre-operative as compared to post-operative radiation whether there is a decreased rate of radiation necrosis, including asymptomatic and symptomatic radiation necrosis.

VIII. To determine for patients with pre-operative as compared to post-operative radiation whether there is a decreased rate of local recurrence.

IX. To determine for patients with pre-operative as compared to post-operative radiation whether there is a decreased rate of leptomeningeal disease.

CORRELATIVE RESEARCH OBJECTIVES:

I. To determine the genetic and molecular alterations of brain metastases seen after radiation versus in the setting of resection alone, including early radiobiologic changes in tissue treated with SRS 24 to 48 hours prior, and to investigate detection rate of corresponding circulating deoxyribonucleic acid (DNA) and/or inflammatory markers in peripheral specimens.

II. To investigate the usefulness of biomarkers and response to radiation in predicting local control and outcomes.

III. To look at cell capture of tumor cells as well as cell free DNA in cerebrospinal fluid (CSF) sampled at the time of surgery, comparing patients receiving neoadjuvant treatment to those that have not.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients undergo surgery on day 1. Within 2 weeks, patients undergo stereotactic radiosurgery.

ARM B: Patients undergo stereotactic radiosurgery on day 1. Within 4 weeks, patients undergo surgery.

After completion of study treatment, patients are followed up at 2 weeks, every 3-4 months for up to 2 years and then periodically for up to 3 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: November 8, 2025
• Est. primary completion date: November 8, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >= 18 years

• Histological or cytological confirmation of solid tumor malignancy and/or clinical history of known or suspected metastatic disease with an intraparenchymal brain tumor consistent with brain metastasis based on clinical and radiologic findings

• Clinical indication for surgical resection of one brain metastasis based on neurosurgery recommendation and patient deemed a surgical candidate

• Clinical indication and plan for stereotactic radiosurgery to all known brain lesions requiring treatment (=< 10 metastases)

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2

• Provide written informed consent or have a legally authorized representative who is responsible for the care and well-being of the potential study participant, provide consent

• Willing to continue follow-up visits, either at the enrolling institution or with a local medical doctor as clinically appropriate, and according to the study timeline. Clinical notes and digital copies of imaging must be provided to the enrolling site if follow-up is done externally

Exclusion Criteria:

• Any of the following:

• Pregnant women

• Nursing women

• Men or women of childbearing potential who are unwilling to employ adequate contraception

• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

• Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy. * NOTE: Patients known to be HIV, but without clinical evidence of an immunocompromised state, are eligible for this trial

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Prior open neurosurgery for malignancy

• Known or clinically suspected primary germ cell tumor, small cell carcinoma, or lymphoma

• History of whole brain radiation therapy (WBRT)

• Known allergy to gadolinium, pacemaker, or other contraindication such as metal implant that is not safe for MRI. Patients with MRI-compatible implants including MRI compatible pacemakers are eligible

• Leptomeningeal metastasis/disease

• A brain metastasis that is located =< 5 mm of the optic chiasm

• Any brain metastasis > 5 cm in size

• > 10 brain metastases

• Indication for surgical resection of >= 2 brain metastases

• Indication for long-term (anticipated greater than 4 weeks) 4 mg dexamethasone equivalent of steroids or bevacizumab

• Actively enrolled on another brain metastases trial that is assessing the efficacy of either radiation or surgical interventions

Related Conditions & MeSH terms

• Malignant Solid Neoplasm
• Metastatic Malignant Neoplasm in the Brain
• Neoplasms

Intervention

Procedure:
• Conventional Surgery
Undergo surgery

Other:
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Radiation:
• Stereotactic Radiosurgery
Undergo stereotactic radiosurgery

Locations

Country	Name	City	State
United States	National Institutes of Neurological Disorders and Stroke, NIH	Bethesda	Maryland
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Central nervous system (CNS) composite endpoint event (CNS-CE event)	The CNS-CE event distributions will be estimated using the Kaplan-Meier method.	Time from study randomization to documentation of the first CNS-CE event, assessed up to 5 years
Secondary	Overall survival (OS)	The distribution of overall survival for both groups of the study will be estimated using the Kaplan-Meier method, and be compared using log-rank tests.	From start of study therapy to death due to any cause, assessed up to 5 years
Secondary	Incidence of adverse events	Will be graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The overall adverse event rates for grade 3 or higher adverse events will be compared using Chi-square or Fisher's exact tests between the 2 treatment groups.	Up to 5 years post treatment
Secondary	CNS-CE event free survival time adjusted for stratification factors	Cox-models will be used that incorporate the stratification factors to test for differences in treatment arms after adjusting for stratification factors listed in section 5.0.	Up to 5 years
Secondary	CNS-CE event free rate	The 6-month CNS-CE rates from the Kaplan-Meier analysis will be compared between the arms.	At 6 months
Secondary	Patient-reported outcome - Quality of Life (QOL)	QOL will be assessed via changes in the Functional Assessment of Cancer Therapy Scale-Brain (FACT-Br) Global score	Baseline to 6 months post treatment
Secondary	Rate of completion of therapies	The rate of completion of planned therapies will be compared using Chi-square or Fisher's exact tests between the 2 treatment groups.	Up to 5 years post treatment
Secondary	Time to systemic therapy	Will be estimated using the Kaplan-Meier method, and will be compared using log-rank tests.	Time to initiation or re-initiation of systemic therapy with pre-operative versus post-operative SRS, assessed up to 5 years
Secondary	Time to regional progression	Will be estimated using the Kaplan-Meier method, and will be compared using log-rank tests.	Up to 5 years post treatment
Secondary	Time central nervous system (CNS) progression	Will be estimated using the Kaplan-Meier method, and will be compared using log-rank tests.	Up to 5 years post treatment
Secondary	Time to subsequent treatment, including whole-brain radiotherapy (WBRT)	Will be estimated using the Kaplan-Meier method, and will be compared using log-rank tests.	Up to 5 years
Secondary	Rate of neurosurgical morbidity	The rates of surgical morbidity including postoperative complications such as wound infection, need for longer hospital stays, or readmission will be compared using Chi-square or Fisher's exact tests between the 2 treatment groups.	Up to 5 years post treatment

External Links

•   Mayo Clinic Clinical Trials