Phase I Study of Fractionated Stereotactic Radiation Therapy

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. We thus propose a phase I study to determine the feasibility and safety of FSRT in patients with brain metastases.

Study Overview

• Status: Recruiting
• Conditions: Brain Metastases
• Intervention / Treatment: Radiation: Fractionated Stereotactic Radiation Therapy

• Study Type: Interventional
• Enrollment (Estimated): 43
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Alyssa Asaro, BA; Phone Number: 718-920-5636; Email: aasaro@montefiore.org

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467
      • Recruiting
      • Montefiore Medical Center
      • Contact: Alyssa Asaro, BA; Phone Number: 718-920-5636; Email: aasaro@montefiore.org

Participation Criteria

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.
• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fractionated Stereotactic Radiation Therapy; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Albert Einstein College of Medicine
• Investigators: Principal Investigator: Madhur Garg, MD, Montefiore

Study record dates

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 8, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: 2017-8344

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes