REMASTer: REcurrent Brain Metastases After SRS Trial

Brain Metastases Clinical Trial

Official title:

REMASTer: REcurrent Brain Metastases After SRS Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05124912
• Other study ID #: REMASTer
• Status: Recruiting
• Phase: N/A
• Start date: May 10, 2022
• Est. completion date: October 2028

Study information

• Verified date: March 2024
• Source: Monteris Medical
• Contact: Christa Seligman
• Phone: 952-463-7747
• Email: cseligman[@]monteris.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 first intervention for radiographic progression after stereotactic radiosurgery (SRS), with or without surgery.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 261
• Est. completion date: October 2028
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Metastases
• Brain Neoplasms
• Necrosis
• Neoplasm Metastasis
• Neoplasms, Second Primary
• Radiation Necrosis
• Recurrence
• Recurrent Tumor

Intervention

Procedure:
• Radiation Therapy
Post-op hypofractionated therapy or no radiation therapy

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)

Locations

Country	Name	City	State
United States	Duke University Hospital	Durham	North Carolina
United States	Kettering Health	Kettering	Ohio
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Monteris Medical

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.
Other	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)
Other	Treatment failure in all cohorts/arms.	Measured in time to salvage therapy	From randomization through 24 months or study exit (whichever comes first)
Other	Overall Survival (OS)	Survival time from randomization	From randomization through 24 months or study exit (whichever comes first)
Other	Freedom from Local Progression (FFLP)	Measure time from procedure to disease progression	From randomization through 24 months or study exit (whichever comes first)
Other	Quality of Life- KPS	Measure change in scoring from baseline over time	From baseline through 24 months or study exit (whichever comes first)
Other	Quality of Life- NCCN Distress	Measure change in scoring from baseline over time	From baseline through 24 months or study exit (whichever comes first)
Other	Quality of Life- FACT-BR	Measure change in scoring from baseline over time	From baseline through 24 months or study exit (whichever comes first)
Other	Cognitive Measure- Trail Making Test	Measure change in scoring from baseline over time	From baseline through 24 months or study exit (whichever comes first)
Other	Cognitive Measure- HVLT	Measure change in scoring from baseline over time	From baseline through 24 months or study exit (whichever comes first)
Primary	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
Primary	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	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.
Secondary	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