Dose Escalation Trial of Neoadjuvant Radiosurgery for the Treatment of Metastatic Brain Tumors

A Phase 1 Dose Escalation Trial of Neoadjuvant Radiosurgery for the Treatment of Metastatic Brain Tumors

The purpose of this study is to study if giving radiation to a brain tumor (a procedure called radiosurgery) before neurosurgery (surgery to remove the tumor) will help to keep brain tissue healthy, while possibly eliminating the need to return for radiation once a patient has healed from neurosurgery. This study will also seek the best radiation dose on a brain tumor based on how well the radiation therapy works and asses the side-effects.

Study Overview

• Status: Active, not recruiting
• Conditions: Brain Metastases
• Intervention / Treatment: Radiation: Neoadjuvant stereotactic radiosurgery; Procedure: Neurosurgical resection

Detailed Description

Radiosurgery is a non-surgical radiation therapy that can deliver targeted radiation to small brain tumors. Radiosurgery is considered to be part of standard of care. Typically for standard of care, radiosurgery is given after a patient has healed from neurosurgery, in an attempt to destroy any cancer cells that may be left after surgery. Patients who agree to participate in this research study will receive radiosurgery before their neurosurgery.

The timing of radiosurgery (pre-operatively) and the dosing to determine the safest dose is considered experimental.

By giving radiation the typical way, after surgery, a larger area of the brain must be covered, which means healthy brain tissue also receives radiation, whereas radiation before surgery will specifically target the tumor.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients with prior histopathological diagnosis of cancer other than small cell lung cancer, lymphoma, and germ cell histologies.
• MR imaging of the brain with findings strongly suggestive of metastatic tumor(s) as assessed by the radiologist.
• MR evidence of at least one brain lesion ≤ 40 mm in maximal diameter that is deemed to be surgically resectable as evaluated by the neurosurgeon and appropriate for SRS. All other brain lesions must be appropriate for SRS alone and treated according to physician preference. Prior neurosurgery and/or prior SRS at a non-overlapping location are permitted at the discretion of the treating physician.
• Written informed consent obtained from subject, or a legally designated power of attorney and ability for subject to comply with the requirements of the study.
• Negative pregnancy test in women of childbearing potential (WOCBP) within 30 days of radiation. WOCBP is a female patient less than 50 years of age or who has menstruated within the last 12 months.
• Patients aged ≥ 18 years.
• Life expectancy ≥ 3 months
• Non-acute KPS ≥ 60%

Exclusion Criteria:

• Patients deemed medically unfit to undergo surgical resection of brain metastasis, such as those who are neurologically or hemodynamically unstable despite appropriate medical interventions.
• Patients who have had whole brain radiation within the previous three months.
• Patients with >4 brain metastases.
• Active or prior: documented inherited hypersensitivity syndromes, certain autoimmune diseases, and certain collagen vascular diseases. For example, any radiation hypersensitivity syndrome, including, but not limited to, ataxia-telangiectasia, Gorlin syndrome, multiple sclerosis, scleroderma, and systemic lupus erythematosus.
• Radiographic or cytologic evidence of leptomeningeal disease.
• Patients receiving methotrexate, adriamycin, epirubicine, or navelbin for one week prior to or concurrently with SRS. Note: All other systemic anti-cancer therapies will be reviewed on a case-by-case basis by study PI to determine if appropriate for study treatment and documented within the research record or EMR.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant stereotactic radiosurgery; Stereotactic radiosurgery will be performed prior to neurosurgical resection of the indexed brain metastasis. The dose of radiation to be administered to the indexed lesion will be established as a function of tumor size.	Radiation: Neoadjuvant stereotactic radiosurgery; Dose escalation of neoadjuvant stereotactic radiosurgery; Procedure: Neurosurgical resection; Surgical resection of newly diagnosed brain metastases; Other Names: craniotomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD)	To determine the maximum tolerated dose of radiosurgery given prior to neurosurgery in subjects with brain metastases of up to 4 cm.	1 month after neurosurgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	To describe the adverse events associated with radiosurgery when administered prior to neurosurgical resection of brain metastases.	1 month after neurosurgery
Describe preliminary rates of image-complete resection		3 years
Describe preliminary rates of local tumor control		3 years
Describe preliminary rates of intracranial control		3 years
Describe preliminary rates of progression-free survival		3 years
Describe preliminary rates of leptomeningeal spread		3 years
Describe preliminary rates of rate of salvage treatment	Salvage treatment is any additional local treatment (surgery or radiation) in the setting of recurrent or progressive disease after the current treatment.	3 years

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center
• Investigators: Principal Investigator: Stephen Shiao, MD, PHD, Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2017
• Primary Completion (Actual): December 15, 2022
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: May 19, 2017
• First Submitted That Met QC Criteria: May 22, 2017
• First Posted (Actual): May 23, 2017

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: neoadjuvant; stereotactic radiosurgery; dose escalation; maximum tolerated dose; brain lesion; metastatic tumor; neurosurgical resection
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplastic Processes; Nervous System Neoplasms; Central Nervous System Neoplasms; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Brain Neoplasms; Surgical Procedures, Operative; Neurosurgical Procedures; Craniotomy
• Other Study ID Numbers: IIT2016-18-Shiao-NeoAdSRS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes