Stereotactic Radiation Therapy Before Surgery for the Treatment of Resectable Brain Metastases

Brain Tumor Clinical Trial

Official title:

Neoadjuvant Stereotactic Radiation Therapy for Resectable Brain Metastases

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04069910
• Other study ID #: 17-000082
• Secondary ID: NCI-2019-05337
• Status: Withdrawn
• Phase: N/A
• Start date: August 26, 2019
• Est. completion date: November 30, 2020

Study information

• Verified date: September 2020
• Source: Jonsson Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial studies how well stereotactic radiation therapy before surgery works in treating patients with cancer that has spread to the brain (brain metastases) and can be removed by surgery (resectable). Stereotactic radiation therapy 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. Giving stereotactic radiation therapy before surgery may make the return of brain metastases less likely and help patients live longer compared to surgery followed by radiation therapy.

Description:

PRIMARY OBJECTIVE:

I. To determine the rate of leptomeningeal failure after neoadjuvant radiation therapy (NaRT) versus (vs) postoperative stereotactic radiosurgery (SRS)/stereotactic radiation therapy (SRT).

SECONDARY OBJECTIVES:

I. Local control of brain metastases. II. Rate of salvage treatment including surgery, SRS, SRT, or whole brain radiation therapy (WBRT).

III. Dose and volume of radiation to adjacent normal brain parenchyma. IV. Rate of symptomatic radiation necrosis/steroid dependency. V. Rate of distant brain failure. VI. To compare overall survival (OS) between the 2 groups. VII. To determine the number of patients who die due to neurologic causes. VIII. To assess quality of life as assessed using Functional Assessment of Cancer Therapy?Brain (FACT?BR).

IX. To evaluate and compare the molecular makeup of tumor tissue in pre vs post radiation settings and determine differences in molecular and germline markers.

X. To evaluate biomarkers and germline markers predicting response.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients undergo 1, 5, or 10 fraction of SRS/SRT radiation. Surgery is performed within 72 hours of radiation therapy.

ARM B: Within 2-5 weeks after standard of care surgery, patients undergo 1, 5, or 10 fraction of SRS/SRT.

After completion of study treatment, patients are followed up every 3 months.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 30, 2020
• Est. primary completion date: November 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Prior histologic diagnosis of cancer other than small cell lung cancer, lymphoma, and germ cell histologies

• 1?4 cerebral metastases per magnetic resonance imaging (MRI) with at least 1 being dominant and eligible for resection

• No prior radiation treatment for the index brain metastases

• Systemic disease staged within previous 8 weeks and not rapidly progressing, with concern of life expectancy > 3 months

• The patients will have been evaluated by the multidisciplinary team, and surgery must be deemed necessary as a result of indications including but not limited to mass effect or symptomatic lesion. Surgery must be deemed non?emergent or non?urgent clinically by the neurosurgeon

• Karnofsky performance status (KPS) >= 70

• No active infections requiring systemic antibiotics

• If a woman is of childbearing potential, a negative serum pregnancy test must be documented. Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) for duration of study participation and for up to 4 weeks following the study treatment

• Ability to understand and willingness to sign a written informed consent

Exclusion Criteria:

• Patient deemed medically unfit to undergo surgical resection of brain metastasis

• Prior whole brain radiotherapy

• Patient with contraindication for imaging with MRI

• Surgery is considered emergent or urgent by the neurosurgeon due to symptoms or concerning mass effect noted on imaging

• Patients who are participating in a concurrent treatment protocol

• At the time of planning, unable to meet dose tolerance of the optic nerve/chiasm

• Tumor located in the brainstem

• Imaging or cytologic evidence of leptomeningeal disease

• Concurrent uncontrolled illness including, but not limited to, any of the following:

Symptomatic congestive heart failure, unstable angina pectoris, psychiatric illness

Related Conditions & MeSH terms

• Brain Neoplasms
• Brain Tumor
• Malignant Neoplasm, Brain
• Neoplasms

Intervention

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

Radiation:
• Stereotactic Radiosurgery
Undergo SRS/SRT

Procedure:
• Therapeutic Conventional Surgery
Undergo standard of care surgery

Locations

Country	Name	City	State
United States	UCLA / Jonsson Comprehensive Cancer Center	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Jonsson Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of leptomeningeal failure	A two-sided Z test with pooled variance will be used at significance level =0.1 to test if there is a difference in leptomeningeal failure rate between the two treatment groups.	Up to 2 years
Secondary	Time to progression	Local control of brain metastases is defined as tumor has not progressed or recurred with no radiographic or symptomatic progression. Using the Response Assessment in Neuro-Oncology (RANO) criteria for brain metastases, progressive disease will be defined as > 20% increase in the sum of the longest diameters of the target lesions; unequivocal progression of enhancing non?target lesions; new lesions; or substantial clinical decline. Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.	Up to 2 years
Secondary	Rate of salvage treatment including surgery, SRS, SRT, or WBRT	Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.	Up to 2 years
Secondary	Dose (Gy) and volume (cc) of radiation to adjacent normal brain parenchyma	Will be compared using t test for continuous outcomes, log rank test for time-to-event outcomes and Z test for binary outcomes.	Up to 2 years
Secondary	Rate of symptomatic radiation necrosis/steroid dependency	Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.	Up to 2 years
Secondary	Rate of distant brain failure	Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.	Up to 2 years
Secondary	Overall survival (OS)	Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.	Up to 2 years
Secondary	Death due to neurological causes	Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.	Up to 2 years
Secondary	Quality of life assessment: FACTBR	Assessed using Functional Assessment of Cancer Therapy-Brain (FACTBR). Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes. The scale is 0 - 4, 0 = "not at all", 4 = "very much". Overall higher ratings mean higher quality of life.	Up to 2 years
Secondary	Genetic expression profiles in pre vs post radiation tumor tissue	Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.	Up to 2 years