Phase I Study of Fractionated Stereotactic Radiation Therapy

Phase 1

Recruiting

• Conditions: Brain Metastases

• Registration Number: NCT03726359
• Lead Sponsor: Albert Einstein College of Medicine

Brief Summary

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. The investigator team thus proposes a Phase I study to determine the feasibility and safety of FSRT in patients with brain metastases.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-12-25
• Study First Submitted: 2018-10-30
• Study First Submitted QC: 2018-10-30
• Study First Posted: 2018-10-31
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-20
• Last Update Posted: 2025-05-22
• Primary Completion: 2027-05
• Study Completion: 2027-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

• Pathologically proven diagnosis of a non-hematological malignancy other than small cell lung cancer within 5 years of registration
• Intact (unresected) brain metastases measuring ≥3 cm and ≤ 6 cm in largest dimension on gadolinium contrast enhanced MRI obtained within 30 days prior to registration OR Surgically resected brain metastasis for which postoperative stereotactic radiotherapy is indicated, with expected target measuring ≥3 cm and ≤6 cm in largest dimension
• Prior Whole Brain Radiation Therapy (WBRT) is allowed
• Age ≥ 18 years
• 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 Stereotactic Radiosurgery (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 (CSF) examination
• Plan for chemotherapy or targeted agents during treatment. Hormonal therapy, immunotherapy targeting PD-1/PD-L1 axis, and bone supportive therapy may be continued during treatment
• 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 lesion with radiotherapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD)	Within 1 year of initiation of treatment	Determine the maximum tolerated dose (MTD) associated with a 20% dose limiting toxicity (DLT). DLT is defined as grade 3 or higher toxicities that occur within 1 year of treatment start and either possibly, probably, or definitively related to radiotherapy (RT).

Secondary Outcome Measures

Name	Time	Method
Response to Treatment	Up to 1 year following initiation of treatment	Response to treatment will be assessed based on the percentage of patients who achieve either a complete response (CR), partial response (PR), or stable disease (SD), or progression (P) in response to FSRT treatment will be determined. Best response will be summarized. Response criteria will be assessed as follows; Complete Response (CR): Defined as follow up imaging which shows that complete radiographic disappearance of brain metastasis. Partial Response (PR): Decrease of \>50% in the size of each lesion radiographically, using perpendicular diameters Stable Disease (SD): 0 to 50% reduction in size of each lesion radiographically, using perpendicular diameters. Progression (P): Defined as \> 25% increase in the size of each lesion or a new, non-contiguous lesion developed outside of the radiosurgical volume.

Trial Locations

Locations (1)

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States