A Dose Escalation Trial of Five Fraction Stereotactic Radiation Therapy for Brain Metastases (RAD1705)

A Phase I Dose Escalation Trial of Five Fraction Stereotactic Radiation Therapy for Brain

This study looks at dose escalation for five fraction stereotactic radiotherapy for patients diagnosed with brain metastases with tumors 2.1-4.0 cm in diameter or 4.1-6.0 cm in diameter.

Study Overview

• Status: Completed
• Conditions: Brain Metastases
• Intervention / Treatment: Radiation: 7 Gy; Radiation: 8 Gy; Radiation: 9 Gy; Radiation: 6 Gy

Detailed Description

This study looks at dose escalation treatment in patients diagnosed with brain metastases. Treatment involve five fraction stereotactic radiotherapy for patients with brain tumors 2.1-4.0 cm in diameter or 4.1-6.0 cm in diameter and dose escalation treatment is delivered only to the single largest tumor while all other tumors are treated with standard of care practices if they are present. A dose escalation schedule is proposed based on the monitoring of CNS toxicity and tumor size of the largest tumor, given it falls into the parameters set on diameter.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Hazelrig-Salter Radiation Oncology Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• All patients must have histologically confirmed malignancy.
• All patients must have imaging suggestive of one or more brain metastases.
• Karnofsky performance status (KPS) ≥ 60
• Age > 18 years
• Patients must provide written informed consent to participate in the study.
• Patients must have less than or equal to 10 brain metastases as identified on brain MRI.

Exclusion Criteria:

• History of surgical resection to the tumor of interest
• History of radiation to the tumor of interest
• History of previous whole brain irradiation
• Receipt of systemic therapy within one week of planned radiation treatment except for hormonal agents.
• Patient is unable to have MRI or MRI contrast.
• Inability to meet the appropriate normal tissue dose constraints secondary to tumor location should result in exclusion of the patient / tumor.
• Patients with a non-index tumor (second tumor) greater than 3 cm in diameter will be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2.1-4.0 cm diameter; Patients will undergo dose escalated five fraction stereotactic radiosurgery for diagnosed brain metastases. Only single largest tumor will be treated with dose escalation. All other tumors (if present) will be treated with standard of care five fraction stereotactic radiosurgery. Starting dose level 7 Gy x 5 fractions	Radiation: 7 Gy; As focal radiation techniques are utilized more frequently in the treatment of brain metastases, there is increasing need to accurately define the appropriate patient and tumor characteristics for focal therapy. Unfortunately, not all patients are good candidates for single fraction stereotactic radiosurgery (SRS) since large tumors and those in unfavorable locations have been associated with unacceptable rates of treatment-related toxicity. Five fraction stereotactic radiation has proven to be a more effective treatment for these patients that aren't good candidates.; Radiation: 8 Gy; As focal radiation techniques are utilized more frequently in the treatment of brain metastases, there is increasing need to accurately define the appropriate patient and tumor characteristics for focal therapy. Unfortunately, not all patients are good candidates for single fraction stereotactic radiosurgery (SRS) since large tumors and those in unfavorable locations have been associated with unacceptable rates of treatment-related toxicity. Five fraction stereotactic radiation has proven to be a more effective treatment for these patients that aren't good candidates.; Radiation: 9 Gy; As focal radiation techniques are utilized more frequently in the treatment of brain metastases, there is increasing need to accurately define the appropriate patient and tumor characteristics for focal therapy. Unfortunately, not all patients are good candidates for single fraction stereotactic radiosurgery (SRS) since large tumors and those in unfavorable locations have been associated with unacceptable rates of treatment-related toxicity. Five fraction stereotactic radiation has proven to be a more effective treatment for these patients that aren't good candidates.
Experimental: 4.1-6.0 cm diameter; Patients will undergo dose escalated five fraction stereotactic radiosurgery for diagnosed brain metastases. Only single largest tumor will be treated with dose escalation. All other tumors (if present) will be treated with standard of care five fraction stereotactic radiosurgery. Starting dose level 6 Gy x 5 fractions.	Radiation: 7 Gy; As focal radiation techniques are utilized more frequently in the treatment of brain metastases, there is increasing need to accurately define the appropriate patient and tumor characteristics for focal therapy. Unfortunately, not all patients are good candidates for single fraction stereotactic radiosurgery (SRS) since large tumors and those in unfavorable locations have been associated with unacceptable rates of treatment-related toxicity. Five fraction stereotactic radiation has proven to be a more effective treatment for these patients that aren't good candidates.; Radiation: 8 Gy; As focal radiation techniques are utilized more frequently in the treatment of brain metastases, there is increasing need to accurately define the appropriate patient and tumor characteristics for focal therapy. Unfortunately, not all patients are good candidates for single fraction stereotactic radiosurgery (SRS) since large tumors and those in unfavorable locations have been associated with unacceptable rates of treatment-related toxicity. Five fraction stereotactic radiation has proven to be a more effective treatment for these patients that aren't good candidates.; Radiation: 6 Gy; As focal radiation techniques are utilized more frequently in the treatment of brain metastases, there is increasing need to accurately define the appropriate patient and tumor characteristics for focal therapy. Unfortunately, not all patients are good candidates for single fraction stereotactic radiosurgery (SRS) since large tumors and those in unfavorable locations have been associated with unacceptable rates of treatment-related toxicity. Five fraction stereotactic radiation has proven to be a more effective treatment for these patients that aren't good candidates.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose of Five Fraction Stereotactic Radiotherapy	To determine the maximum tolerated dose of five fraction stereotactic radiotherapy for patients with either tumors 2.1-4.0 cm in diameter or 4.1-6.0 cm in diameter	1-2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Toxicity of Five Fraction Stereotactic Radiotherapy Using Adverse Event Questionnaire	To assess the acute toxicity of five fraction stereotactic radiotherapy for tumors 2-6 cm in diameter using the RAD 1705 Adverse Events Assessment. This assessment was created within our department and will be used specifically for this study.	1-2 years
Late Toxicity of Five Fraction Stereotactic Radiotherapy Using Adverse Event Questionnaire	To assess the late toxicity of five fraction stereotactic radiotherapy for tumors 2-6 cm in diameter using the RAD 1705 Adverse Events Assessment. This assessment was created within our department and will be used specifically for this study.	1-2 years
Rate of Local Tumor Control With Five Fraction Stereotactic Radiotherapy Using Adverse Event Questionnaire	To determine the rate of local tumor control with five fraction stereotactic radiotherapy for tumors 2-6 cm in diameter using the RAD 1705 Adverse Events Assessment. This assessment was created within our department and will be used specifically for this study.	1-2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of Capturing Patient Reported Outcomes Electronically Using FACT-Br Questionnaire	To assess the feasibility of capturing patient reported outcomes with the Functional Assessment of Cancer Therapy-Brain Questionnaire (FACT-Br) electronically in the Radiation Oncology clinic	1-2 years

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: John B Fiveash, MD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2018
• Primary Completion (Actual): January 19, 2024
• Study Completion (Actual): October 1, 2025

Study Registration Dates

• First Submitted: December 29, 2017
• First Submitted That Met QC Criteria: January 19, 2018
• First Posted (Actual): January 26, 2018

Study Record Updates

• Last Update Posted (Estimated): November 4, 2025
• Last Update Submitted That Met QC Criteria: October 14, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Brain Metastases; Stereotactic Radiosurgery
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms
• Other Study ID Numbers: IRB-300001065

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No