Clinical trial NCT03163368: Dose Escalation Trial of Neoadjuvant Radiosurgery for the Treatment of Metastatic Brain Tumors
Official title: A Phase 1 Dose Escalation Trial of Neoadjuvant Radiosurgery for the Treatment of Metastatic Brain Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Brain Metastases
Keywords: metastatic tumor
brain lesion
stereotactic radiosurgery
neoadjuvant
maximum tolerated dose
dose escalation
neurosurgical resection
Lead sponsor: Cedars-Sinai Medical Center
Sponsor class: OTHER
First posted: 2017-05-23
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: 1 month after neurosurgery
Secondary outcomes:
measure: Adverse events
timeFrame: 1 month after neurosurgery
measure: Describe preliminary rates of image-complete resection
timeFrame: 3 years
measure: Describe preliminary rates of local tumor control
timeFrame: 3 years
measure: Describe preliminary rates of intracranial control
timeFrame: 3 years
measure: Describe preliminary rates of progression-free survival
timeFrame: 3 years
measure: Describe preliminary rates of leptomeningeal spread
timeFrame: 3 years
measure: Describe preliminary rates of rate of salvage treatment
timeFrame: 3 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
Study officials:
affiliation: Cedars-Sinai Medical Center
name: Stephen Shiao, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: