Phase I Study of Fractionated Stereotactic Radiation Therapy

Study Overview
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Brief Summary
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There is a lack of prospective trial data and consensus guidelines describing the use of Fractionated Stereotactic Radiation Therapy (FSRT) in the treatment of brain metastases. There has been no prospective dose escalation study performed to date to determine the maximum tolerated dose (MTD) in patients treated with FSRT. Prescription doses in the series described above ranged from 18 Gy to 42 Gy, delivered in 3 to 12 fractions. The results of this study will be used to plan future Phase II/III studies to determine the efficacy of different dose fractionation schedules of FSRT. We thus propose a phase I study to determine the feasibility and safety of FSRT in patients with brain metastases.

Official Title
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Phase I TITE-CREM Dose Escalation Study of Fractionated Stereotactic Radiation Therapy (FSRT) in Unresected Brain Metastases

Conditions
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Brain Metastases

Intervention / Treatment
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* Radiation: Fractionated Stereotactic Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically proven diagnosis of a non-hematological malignancy other than small cell lung cancer within 5 years of registration. Patients with measurable brain metastases who have a gadolinium contrast enhanced MRI obtained within 30 days prior to registration. Patients with CT based diagnostic imaging without MRI will not be allowed to enroll on this trial. No surgical resection of the target lesion, defined as ≥3 cm but ≤6 cm in size on MRI of the Brain with contrast Prior Whole Brain Radiation Therapy (WBRT) is allowed Age ≥ 18 years Karnofsky performance status ≥ 60 or ECOG ≤2 Women of childbearing potential and male participants must practice adequate contraception History/Physical examination within 30 days prior to registration Life expectancy>3 months Patients are allowed to enroll if previously treated to other lesions with SRS Patients with multiple lesions are allowed, as long there is one dominant lesion that will be treated with FSRT. Other lesions may be treated concurrently with SRS or FSRT at the discretion of the treating physician but will not contribute to the study endpoints. Exclusion Criteria: Patients with definitive leptomeningeal metastases, based on cerebrospinal fluid examination (CSF) Plan for chemotherapy or targeted agents during treatment. All hormonal therapy and bone supportive therapy may be continued while patient is on study. Contraindication to enhanced MRI imaging such as implanted metal devices. However, patients with implanted devices which are MRI compatible are allowed. Patients with measurable brain metastasis resulting from small cell lung cancer and germ cell malignancy Uncontrolled intercurrent illness such as congestive heart failure, unstable angina, cardiac arrhythmia, and uncontrolled seizure activity. Previous treatment of the target lesions with radiotherapy.

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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fractionated Stereotactic Radiation Therapy<br>This study is unique in that it employs a continuous reassessment methodology (CRM) to determine the Maximum Tolerated Dose. Information for the proper dose level for each subsequent patient enrolled will be determined based on DLTs from previous patients enrolled in the trial. | Radiation: Fractionated Stereotactic Radiation Therapy<br>* Initial starting dose will be 7 Gy x5= 35 Gy delivered to the planning target volume (PTV). Radiotherapy will be delivered every other day so that the SBRT schedule is completed within 1.5-2 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) | The primary endpoint of this study is to determine the maximum tolerated dose (MTD) associated with a 20% dose limiting toxicity (DLT). | 1 year |