Phase I Study of Fractionated Stereotactic Radiation Therapy

May 20, 2025 updated by: Albert Einstein College of Medicine

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

43

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Fractionated Stereotactic Radiation Therapy (FSRT)
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 (FSRT)
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 Stereotactic Body Radiation Therapy (SBRT) schedule is completed within 1.5-2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD)
Time Frame: 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).
Within 1 year of initiation of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response to Treatment
Time Frame: 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.
Up to 1 year following initiation of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Albert Einstein College of Medicine

Investigators

  • Principal Investigator: Madhur Garg, MD, Montefiore Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 25, 2017

Primary Completion (Estimated)

May 1, 2027

Study Completion (Estimated)

May 1, 2027

Study Registration Dates

First Submitted

October 30, 2018

First Submitted That Met QC Criteria

October 30, 2018

First Posted (Actual)

October 31, 2018

Study Record Updates

Last Update Posted (Actual)

May 22, 2025

Last Update Submitted That Met QC Criteria

May 20, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017-8344

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Brain Metastases

Clinical Trials on Fractionated Stereotactic Radiation Therapy (FSRT)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Romania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe