REMASTer: REcurrent Brain Metastases After SRS Trial

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

Study Overview

• Status: Recruiting
• Conditions: Brain Metastases; Radiation Necrosis; Recurrent Tumor; Recurrent Metastases
• Intervention / Treatment: Procedure: Radiation Therapy; Procedure: Laser Interstitial Thermal Therapy; Drug: Steroid Therapy

• Study Type: Interventional
• Enrollment (Estimated): 261
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christa Seligman; Phone Number: 952-463-7747; Email: cseligman@monteris.com

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Hospital
      • Principal Investigator: Peter Fecci, MD
      • Contact: Beth Perry; Email: beth.perry@duke.edu
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Wake Forest Baptist Medical Center
      • Contact: Wendy Jenkins; Email: wejenkin@wakehealth.edu
      • Principal Investigator: Adrian Laxton, MD
  • Ohio
    • Kettering, Ohio, United States, 45429
      • Recruiting
      • Kettering Health
      • Contact: Allison Dymacek; Email: allison.dymacek@ketteringhealth.org
      • Principal Investigator: Mark Hoeprich, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

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

1. Patients with radiographically proven (by gadolinium-enhanced [Gd-] MRI) parenchymal brain metastases from histologically confirmed non-central nervous system (CNS) cancer.
2. Patients with a "targetable", bidimensionally-measurable, intracranial lesion that is radiographically recurrent after previous treatment with SRS +/- surgery (craniotomy or LITT). 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. To be "targetable" for this study, the lesion should be coverable through a planned single LITT trajectory and thus have a maximum perpendicular diameter (perpendicular to the laser trajectory) of 3 cm. An intra-operative decision to utilize two trajectories is acceptable and patient may remain on study.
3. Patient must be at least 3 months post initial SRS treatment of the target lesion
4. Target lesion must be amenable to undergo surgical biopsy and LITT treatment as determined by the treating neurosurgeon.
5. Frozen pathology diagnosis must be attainable.
6. Patient must be symptomatically stable for a minimum of 3 days prior to the procedure date on a on a max total daily steroid dose equivalent to 4mg of Dexamethasone.
7. ≥18 years of age
8. KPS ≥70
9. Patient is able and willing to complete study requirements

10. Patients with adequate hematologic parameters (all tests to be performed within <4 weeks of biopsy):

    1. ANC ≥ 1.5 X 109/L
    2. Platelet count ≥ 100 x 109/L
11. Blood chemistry laboratory value for serum creatinine < 1.5 x ULN (test to be performed within <4 weeks of biopsy)
12. 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)
13. All patients of reproductive potential must agree to use an effective method of contraception during the study
14. 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:

1. 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 RANO criteria. Of note, there is no exclusion for total number of metastases. However, only one lesion can be selected to be the targeted lesion and this lesion alone may be ablated during the study procedure.
2. Patients with concomitant newly diagnosed intracranial metastases (concurrent with the targetable radiographically progressive lesion), as these will require prioritized and different treatment approaches.
3. Prior bevacizumab use within 4 weeks of study initiation
4. Patients with additional concurrent malignancies requiring active treatment, except non-melanoma skin cancer, or in-situ cancer of the cervix
5. 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
6. Inability to tolerate or contraindication to steroid therapy (i.e., dexamethasone)
7. Deemed ineligible or unable to tolerate SRS therapy by treating neurosurgeon and/or radiation oncologist
8. Patients with any condition that would prohibit them from undergoing a surgical procedure, at the discretion of the treating physician team
9. Patients unwilling or unable to give consent for participation
10. Patients unable to comply with study requirements
11. Patients with diffuse leptomeningeal disease
12. Patients with rapidly progressing extracranial disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.	Procedure: Laser Interstitial Thermal Therapy; Minimally invasive technique to necrotize intracranial lesions using the NeuroBlate® System (NBS); Drug: Steroid Therapy; Best medical management with steroid therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progressive Disease Cohort	Determine the effectiveness of LITT using the NeuroBlate® System with or without repeat SRS on recurrent brain metastases, as measured by freedom from local progression.	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
Radiation Necrosis Cohort	Determine the effectiveness of LITT using the NeuroBlate System versus standard medical management as measured by time to steroid independence without escalation of care, measured in days from LITT procedure, defined as freedom from steroids for a period of four weeks without escalation of care.	Assessed for a three month period from time of randomization to steroid freedom without escalation of care.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progressive Disease Cohort: Overall Survival	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.
Radiation Necrosis Cohort: Freedom from Local Progression (FFLP) or Neurological Death	Compare treatment approaches with respect to FFLP or neurologic death	Compare treatment approaches with respect to overall survival, defined as time from study biopsy to death or study exit, up to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Explore the relationship between radiographic features and biopsy results	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.	From randomization through 24 months or study exit (whichever comes first)
Treatment failure in all cohorts/arms.	Measured in time to salvage therapy	From randomization through 24 months or study exit (whichever comes first)
Overall Survival (OS)	Survival time from randomization	From randomization through 24 months or study exit (whichever comes first)
Freedom from Local Progression (FFLP)	Measure time from procedure to disease progression	From randomization through 24 months or study exit (whichever comes first)
Quality of Life- KPS	Measure change in scoring from baseline over time	From baseline through 24 months or study exit (whichever comes first)
Quality of Life- NCCN Distress	Measure change in scoring from baseline over time	From baseline through 24 months or study exit (whichever comes first)
Quality of Life- FACT-BR	Measure change in scoring from baseline over time	From baseline through 24 months or study exit (whichever comes first)
Cognitive Measure- Trail Making Test	Measure change in scoring from baseline over time	From baseline through 24 months or study exit (whichever comes first)
Cognitive Measure- HVLT	Measure change in scoring from baseline over time	From baseline through 24 months or study exit (whichever comes first)
Describe Quality of Life (QoL) and cognition over time	Change from baseline at each follow-up assessment for each cognitive and QoL subscale	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.

Collaborators and Investigators

• Sponsor: Monteris Medical

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: October 26, 2021
• First Submitted That Met QC Criteria: November 16, 2021
• First Posted (Actual): November 18, 2021

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Brain Metastases; SRS; LITT; Laser Interstitial Thermal Therapy; Radiation Necrosis; Stereotactic Radiosurgry
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Disease Attributes; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Recurrence; Brain Neoplasms; Necrosis; Neoplasms, Second Primary
• Other Study ID Numbers: REMASTer

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