REMASTer: REcurrent Brain Metastases After SRS Trial

Sponsor

Monteris Medical (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05124912

Collaborator

(none)

154

Enrollment

Locations

Arms

49.7

Anticipated Duration (Months)

Patients Per Site

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Randomized, post-market multi-center study investigating the efficacy of two sets of treatment algorithms in brain metastases (BM) patients at the time of radiographic progression evidence after stereotactic radiosurgery (SRS), with or without resection.

Condition or Disease	Intervention/Treatment	Phase
Brain Metastases Radiation Necrosis Recurrent Tumor Recurrent Metastases	Procedure: Radiation Therapy Drug: Steroid Therapy Procedure: Laser Interstitial Thermal Therapy	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

154 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

REMASTer: REcurrent Brain Metastases After SRS Trial

Actual Study Start Date :

May 10, 2022

Anticipated Primary Completion Date :

Dec 1, 2025

Anticipated Study Completion Date :

Jul 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Other: Recurrent Tumor Receives Laser Interstitial Thermal Therapy (LITT) followed by surveillance or Receives Laser Interstitial Thermal Therapy (LITT) followed by hypofractionated radiation therapy (RT).	Procedure: Radiation Therapy Post-op hypofractionated therapy or no radiation therapy Procedure: Laser Interstitial Thermal Therapy Minimally invasive technique to necrotize intracranial lesions using the NeuroBlate® System (NBS)
Other: Radiation Necrosis Receives Laser Interstitial Thermal Therapy (LITT) and best medical management with steroids or Receives best medical management with steroids.	Drug: Steroid Therapy Best medical management with steroid therapy Procedure: Laser Interstitial Thermal Therapy Minimally invasive technique to necrotize intracranial lesions using the NeuroBlate® System (NBS)

Arm

Intervention/Treatment

Other: Recurrent Tumor

Receives Laser Interstitial Thermal Therapy (LITT) followed by surveillance or Receives Laser Interstitial Thermal Therapy (LITT) followed by hypofractionated radiation therapy (RT).

Procedure: Radiation Therapy

Post-op hypofractionated therapy or no radiation therapy

Procedure: Laser Interstitial Thermal Therapy

Minimally invasive technique to necrotize intracranial lesions using the NeuroBlate® System (NBS)

Other: Radiation Necrosis

Receives Laser Interstitial Thermal Therapy (LITT) and best medical management with steroids or Receives best medical management with steroids.

Drug: Steroid Therapy

Best medical management with steroid therapy

Procedure: Laser Interstitial Thermal Therapy

Minimally invasive technique to necrotize intracranial lesions using the NeuroBlate® System (NBS)

Outcome Measures

Primary Outcome Measures

Recurrent Tumor Cohort [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months]
Determine the effectiveness of LITT using the NeuroBlate® System in combination with repeat SRS on recurrent brain metastases vs LITT alone
Radiation Necrosis Cohort [Assessed for a three month period from time of randomization to steroid cessation]
Determine the effectiveness of LITT using the NeuroBlaste System versus standard medical management via time to steroid cessation, measured in days from LITT procedure, defined as freedom from steroids for a period of four weeks.

Secondary Outcome Measures

Compare treatment approaches with respect to overall survival [Compare treatment approaches with respect to overall survival, defined as time from study biopsy to death or study exit, up to 24 months.]
Compare treatment approaches, as defined by the assigned study arms after randomization and any subsequent salvage treatment following treatment failure, in respect to overall survival.

Other Outcome Measures

Describe Quality of Life (QoL) and cognition observed over time [From enrollment through 24 months or study exit (whichever comes first). Measurements occur at baseline, post-op visit, 1 month visit, and each subsequent follow up visit until study exit or at 24 months, whichever comes first.]
Change from baseline at each follow-up assessment for each cognitive and QoL subscale
Explore the relationship between radiographic features and biopsy results [From randomization through 24 months or study exit (whichever comes first)]
Explore radiographic features, measured as change in enhancing lesion volume and T2 FLAIR volume, at each follow up imaging timepoint (post-op and months 1,3,6,9,12,18,24) or until study exit.
Treatment failure in all cohorts/arms. [From randomization through 24 months or study exit (whichever comes first)]
Measured in time to salvage therapy
Overall Survival (OS) [From randomization through 24 months or study exit (whichever comes first)]
Survival time from randomization
Freedom from Local Progression (FFLP) [From randomization through 24 months or study exit (whichever comes first)]
Measure time from procedure to disease progression
Quality of Life- KPS [From baseline through 24 months or study exit (whichever comes first)]
Measure change in scoring from baseline over time
Quality of Life- NCCN Distress [From baseline through 24 months or study exit (whichever comes first)]
Measure change in scoring from baseline over time
Quality of Life- FACT-BR [From baseline through 24 months or study exit (whichever comes first)]
Measure change in scoring from baseline over time
Cognitive Measure- Trail Making Test [From baseline through 24 months or study exit (whichever comes first)]
Measure change in scoring from baseline over time
Cognitive Measure- HVLT [From baseline through 24 months or study exit (whichever comes first)]
Measure change in scoring from baseline over time

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

Patients with radiographically proven (by gadolinium-enhanced [Gd-] MRI) parenchymal brain metastases from histologically confirmed non-central nervous system (CNS) cancer.
Patients with a "targetable", bidimensionally-measurable, intracranial lesion of minimum 1.5 cm (1.5 cm being the product of the largest perpendicular diameters as defined by Gd-MRI) that is radiographically recurrent after previous treatment with SRS +/- surgery. To classify a lesion as radiographically progressive, the lesion must demonstrate a ≥ 25% increase in size following treatment based on the Neuro-Oncology Criteria of Tumor Response for CNS Tumors, with a lesion size of ≥ 1.5cm (1.5cm being the product of the largest perpendicular diameters). To be "targetable" for this study, the lesion should be coverable through a single LITT trajectory and thus have a maximum perpendicular diameter (perpendicular to the laser trajectory) of 3 cm.
Patient must be at least 3 months post initial SRS treatment for the target lesion
Target lesion must be amenable to undergo surgical biopsy and LITT treatment as determined by the treating neurosurgeon.
Frozen pathology diagnosis must be attainable.
Patient must be symptomatically stable on a max steroid dose of 2 mg twice daily for a minimum of 3 days prior to procedure date.
≥18 years of age
KPS ≥70
Patient is able and willing to complete study requirements
Patients with adequate hematologic parameters (all tests to be performed within <4 weeks of biopsy):
ANC ≥ 1.5 X 109/L
Platelet count ≥ 100 x 109/L
Blood chemistry laboratory value for serum creatinine < 1.5 x ULN (test to be performed within <4 weeks of biopsy)
Female patients must have a negative serum pregnancy test at screening. (Not applicable to patients with bilateral oophorectomy and/or hysterectomy or to those patients who are postmenopausal)
All patients of reproductive potential must agree to use an effective method of contraception during the study
Patients must be accessible for follow-up

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

Patients with greater than 3 progressing lesions at time of enrollment. To classify as a radiographically progressive, lesion must demonstrate a ≥ 25% increase in size following treatment based on the Neuro-Oncology Criteria of Tumor Response for CNS Tumors, with a lesion size of ≥ 1cm (1cm being the product of the largest perpendicular diameters). Of note, there is no exclusion for total number of metastases. However, only one lesion can be selected to be the indexed lesion.
Patients with concomitant newly diagnosed intracranial metastases (concurrent with the targetable radiographically progressive lesion), as these will require prioritized and different treatment approaches.
Prior bevacizumab use within 4 weeks of study initiation
Patients with concurrent malignancies requiring active treatment, except non-melanoma skin cancer, or in-situ cancer of the cervix
Patients with a serious active infection or other serious underlying medical conditions that would impair the ability of the patient to complete the protocol related QOL questionnaires and cognition assessments
Inability to tolerate or contraindication to steroid therapy (i.e., dexamethasone)
Deemed ineligible or unable to tolerate SRS therapy by treating neurosurgeon and/or radiation oncologist
Patients with any condition that would prohibit them from undergoing a surgical procedure, at the discretion of the treating physician team
Patients unwilling or unable to give consent for participation
Patients unable to comply with study requirements