Fractionated Stereotactic Radiosurgery for Large Brain Metastases

Study Overview
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Brief Summary
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This is a research trial that seeks to break up the total radiation dose into multiple smaller radiation treatments, termed fractionated stereotactic radiosurgery (FSRS) which may make the treatment feasible. Fractionated sterotatcic radiation, the risks of FSRS, and possible costs will be described later in this document. This clinical trial is for people who have had no prior whole brain radiation.

Official Title
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PHASE I STUDY OF FRACTIONATED STEREOTACTIC RADIOSURGERY FOR LARGE BRAIN METASTASES

Conditions
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Large Brain Mets

Intervention / Treatment
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* Radiation: Fractionated Stereotactic Radiosurgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients ≥ 18 years of age A life expectancy of at least 12 weeks with a Karnofsky performance status of at least 70 (Appendix II) The target lesion(s) can be accurately measured in at least one dimension according to RECIST No prior radiotherapy to the brain Previous or concurrent systemic or targeted chemotherapy is allowed. Patients must have an extra-cranial primary tumor diagnosis Patients will have no more than 3 distinct lesions within the brain. At least 1 lesion must be a minimum of 3cm in greatest dimension, no larger than 5cm which will be treatable by fractionated stereotactic radiosurgery The additional lesions will each be treated with single fraction stereotactic radiosurgery Patient may be on steroids or anti-epileptics Must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks and discomforts Patients do not need a histologically proven diagnosis of brain mets Exclusion Criteria: Symptomatic patients in need of surgery to the target lesion Four or more newly-diagnosed lesions Prior surgical resection of targeted tumor Prior WBRT Primary brain tumor Pregnant or breast-feeding patients Primary tumor histology of lymphoma, leukemia, multiple myeloma or germ cell tumor

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Fractionated Stereotactic Radiosurgery<br>24 to 36 Gy in 3 fractions (8-12 Gy/fx). | Radiation: Fractionated Stereotactic Radiosurgery<br>* SRS SBRT CyberKnife Trilogy True Beam Radiosurgery<br>* Other names: Radiosurgery;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) | The proportion patients experiencing DLT at each dose; toxicities will be tabulated by category and grade. The dose-toxicity function, describing the probability of DLT at each dose, will be estimated using logistic regression, along with likelihood ratio profile confidence intervals. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local control of disease | Proportion of patients with local control at each dose. Local control is defined as stable disease (SD), partial response (PR), or complete response (CR) in the target lesion, per RECIST v1.1. Complete Response (CR): the disappearance of a target lesion. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm., Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study. | Up to 24 months after completion of treatment | 
| Regional intracranial failure | Proportion of patients having local failure (progressive disease (PD)) within the target lesion. Per RECIST v1.1: Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions, taking as a reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). | Up to 24 months after completion of treatment | 
| Functional Assessment of Cancer Therapy - Brain (FACT-Br) | Functional Assessment of Cancer Therapy - Brain (FACT-Br) is a 50 item, self-administered questionnaire used to assess Quality of Life, including, Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, and Functional Well-Being. The assessment takes 10-15 minutes to completed and is scored using a 5 point Likert-type scale. Scores range from 0-250, with higher scores indicating better Quality of Life. | At 30 days post treatment, 8 -12 weeks post treatment, and at time of each follow-up; Up to 24 months after completion of treatment |