MedPath

Post-Surgical Stereotactic Radiotherapy (SRT) Versus GammaTile-ROADS (Radiation One and Done Study)

Phase 3
Recruiting
Conditions
Brain Metastases
Interventions
Device: Gamma Tile-Surgically Targeted Radiation Therapy (STaRT)
Radiation: Stereotactic Radiation Therapy
Registration Number
NCT04365374
Lead Sponsor
GT Medical Technologies, Inc.
Brief Summary

This trial will be a randomized controlled study comparing the efficacy and safety of intraoperative radiation therapy using GammaTilesTM (GT) versus SRT 3-4 weeks following metastatic tumor resection which is the current standard of care.

Detailed Description

GammaTile therapy results in improved clinical outcomes; however, the data is a single site experience with a limited number of subjects, including only 12 of which were patients with metastatic brain tumors. The primary objective of this randomized, controlled trial is to compare the efficacy and safety of intraoperative radiation therapy using GammaTile® (GT) versus SRT 3-4 weeks following metastatic tumor resection which is the current standard of care. The data collected in this trial design will allow for a direct comparison of a variety of outcomes including local control, overall survival, functional status, quality of life, neurocognitive status, and safety in the target population. In order to support direct comparisons, subjects will be randomized to the two equally sized arms (1:1) based on the following stratification factors: age (\<60 vs ≥60), duration of extracranial disease control (≤3 months vs \>3 months), number of metastases (one, 2-4 total, 5-6 total ), histology (breast cancer, lung cancer, melanoma, other), the maximal diameter of the index lesion (≤3 cm, \>3 cm to ≤5cm, \>5cm to ≤7cm) and use of prior or current immunotherapy (yes vs no).

An index lesion meeting the criteria of ≥ 2.0-7.0 cm in maximum diameter and appropriate for gross total resection (GTR), will be identified and up to five (5) other unresected, previously untreated lesions in a patient will be allowed. After resection of the index lesion, the surgical bed will be treated with adjunct radiation (either GT or SRT) thereby following the standard of care guidelines (NCCN Guidelines, 2019). Additionally, all unresected, previously untreated metastatic lesions will be treated with stereotactic radiosurgery alone, which also adheres to standard of care guidelines (NCCN Guidelines, 2019).

GammaTile is an FDA-cleared means of rapid dose delivery of radiation therapy directly to the tumor bed with predictable dosimetry at the immediate time of resection, and an intense but localized radiation treatment may confer a reduced risk for radiation necrosis compared to other therapies. It is typically easily placed with minimal additional operative time and limited staff radiation exposure.

Given these benefits, the rationale for conducting this randomized controlled comparison study is to generate additional data, to further support the use of this new FDA-cleared method of delivering radiation therapy in the setting of newly diagnosed brain metastases.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
180
Inclusion Criteria
  1. Patients aged 18 years old and above. Eligibility is restricted to this age group given that the battery of neurocognitive tests utilized in this protocol are not developed or validated for use in a younger population.
  2. One to six newly diagnosed brain metastases, identified on the screening MRI, from an extracranial primary tumor.
  3. Only one lesion, designated the index lesion, is planned for surgical resection. The index lesion must be between 2.0 and 7.0 cm in maximal extent on the screening MRI, and gross total resection is expected by the neurosurgeon.
  4. Non-index lesions must measure ≤ 4.0 cm in maximal extent on the screening MRI brain scan. The unresected lesions will be treated with SRT as outlined in the treatment section of the concept.
  5. All metastases must be located ≥ 5 mm from the optic chiasm and outside the brainstem. Dural based metastasis are eligible.
  6. Previous and/or concurrent treatment with investigational or FDA approved systemic therapies (e.g., chemotherapy, targeted therapeutics, immunotherapy) are permitted and must follow protocol guidelines as follows: Systemic therapy is allowed a minimum of one week from last systemic therapy cycle to surgical resection, and one week after surgical resection to allow a minimum of one week before starting/resuming systemic therapy, depending on the specific systemic agent(s), as recommended by medical/neuro-oncology. Systemic therapy is not allowed 1 day before SRT, the same day as the SRT, or 1 day after the completion of the SRT or longer, depending on the specific systemic agent(s), as recommended by medical/neuro-oncology. Agents that are delivered by implant or depot injections (such as hormonal therapies) are excluded from these restrictions.
  7. Karnofsky Performance Scale (KPS) score of ≥ 70. Patients with KPS < 70 can be enrolled if their baseline KPS within 14 days of screening was estimated ≥ 70 and surgical management is expected to improve KPS to ≥ 70.
  8. Stable systemic disease or reasonable systemic treatment options predicting a life expectancy of ≥6 months.
  9. Ability to complete an MRI of the head with contrast
  10. Adequate renal and hepatic function to undergo surgery, in investigators opinion.
  11. For women of childbearing potential only, a negative urine or serum pregnancy test done <7 days prior to randomization is required. Women must be willing to notify investigator immediately if they become pregnant at any time during the trial period.
  12. Men and women of childbearing potential must be willing to employ adequate contraception throughout the study and for men for up to 3 months after completing treatment.
  13. Subjects must be fluent in English, Spanish, or another language the study site is prepared to obtain informed consent for in this trial. English speaking subjects will complete Neurocognitive assessments. Non-English-speaking subjects are trial-eligible but will not complete the Neurocognitive assessments as the psychometric properties for translated tests are either not known or not as robust.
  14. Willingness and ability to provide written informed consent and HIPAA authorization prior to performance of any study-related procedures. A legally authorized representative may provide consent if the potential subject lacks the capacity to provide consent themselves.

Exclusion Criteria

  1. Age <18 years.
  2. Karnofsky Performance Scale (KPS) score of <70. Patients with KPS < 70 can be enrolled if their baseline KPS within 14 days of screening was estimated ≥ 70 and surgical management is expected to improve KPS to ≥ 70.
  3. Sensitivity to bovine (cow) derived materials including collagen products.
  4. Past radiation or surgical therapy to the index lesion or the newly diagnosed non-index lesion(s) is exclusionary. However, up to a total of 2 prior courses of SRT treatment to previously diagnosed lesions are allowed as long as any treated lesions are were ≥15mm from the index lesion.
  5. Patients with >6 newly diagnosed metastases on screening MRI
  6. Pregnant patients.
  7. Primary germ cell tumor, small cell carcinoma, or lymphoma.
  8. Leptomeningeal metastasis (LMD). Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined as radiologic or clinical evidence of leptomeningeal involvement with or without positive cerebrospinal fluid (CSF) cytology.
  9. Prior WBRT for brain metastases.
  10. Concomitant therapy that, in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of the study device.
  11. Comorbid psychiatric or neurologic disease or injury impacting cognition, in the opinion of the treating physician, that might impair patient's ability to understand or comply with the requirements of the study or to provide consent
  12. Subjects who, in the investigator's opinion, are unable to understand the protocol or to give informed consent, have a history of poor cooperation, noncompliance with medical treatment, or difficulty in returning for follow up care. A legally authorized representative may provide consent if the potential subject lacks the capacity to provide consent themselves.
Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Surgical Resection and GammaTile TherapyGamma Tile-Surgically Targeted Radiation Therapy (STaRT)Surgical Resection and GammaTile Therapy
Surgical Resection and Stereotactic Radiation TherapyStereotactic Radiation TherapySurgical Resection and Stereotactic Radiation Therapy
Primary Outcome Measures
NameTimeMethod
Surgical bed recurrence-free survival (SB-RFS) from the time of randomization up to 2 years post radiation.up to 2 years post-radiation

Surgical bed control is defined as the absence of new nodular contrast enhancement in the index lesion surgical bed.

Secondary Outcome Measures
NameTimeMethod
Overall Survivalup to 3 years

Survival of subjects

Hopkins Verbal Learning Test (HVLT-R)up to 24 months

An assessment of neurocognitive status

Controlled Oral Word Association Test (COWAT)up to 24 months

An assessment of neurocognitive status

Trail Making Tests (TMT) Parts A and Bup to 24 months

An assessment of neurocognitive status

Barthel ADLup to 24 months

An assessment of physical functioning status

Functional Assessment of Cancer Therapy-Brain (FACT-Br)up to 9 months

An assessment of quality of life (QOL)

Linear Analog Scale Assessments (LASA)up to 9 months

An assessment of quality of life (QOL)

Trial Locations

Locations (37)

Baptist MD Anderson Cancer Center- Jacksonville

🇺🇸

Jacksonville, Florida, United States

HonorHeath Scottsdale Osborn Medical Center

🇺🇸

Phoenix, Arizona, United States

University of Arkansas Medical Center

🇺🇸

Little Rock, Arkansas, United States

Keck Hospital of Usc

🇺🇸

Los Angeles, California, United States

HCA Florida First Coast Neurology- Orange Park

🇺🇸

Orange Park, Florida, United States

Advent health Orlando

🇺🇸

Orlando, Florida, United States

Orlando Health

🇺🇸

Orlando, Florida, United States

Florida Health Sciences Center, Inc. d/b/a Tampa General Hospital

🇺🇸

Tampa, Florida, United States

Piedmont Hospital

🇺🇸

Atlanta, Georgia, United States

Winship Cancer Institute of Emory University

🇺🇸

Atlanta, Georgia, United States

RUSH University

🇺🇸

Chicago, Illinois, United States

Indiana University, IU Health Methodist Hospital

🇺🇸

Indianapolis, Indiana, United States

The University Of Kansas Cancer Center

🇺🇸

Kansas City, Kansas, United States

University of Louisville

🇺🇸

Louisville, Kentucky, United States

Henry Ford Health

🇺🇸

Detroit, Michigan, United States

Abbott Northwestern Hospital

🇺🇸

Minneapolis, Minnesota, United States

University Of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

Ellis Fischel Cancer Center at University of Missouri

🇺🇸

Columbia, Missouri, United States

SSM Health Saint Louis University Hospital

🇺🇸

Saint Louis, Missouri, United States

Dartmouth-Hitchcock

🇺🇸

Lebanon, New Hampshire, United States

HMH Jersey Shore University Medical Center

🇺🇸

Neptune, New Jersey, United States

Albany Medical Center

🇺🇸

Albany, New York, United States

Memorial Sloan Kettering

🇺🇸

New York, New York, United States

Westchester Medical Center

🇺🇸

Westchester, New York, United States

University of North Carolina Health

🇺🇸

Chapel Hill, North Carolina, United States

ECU Health

🇺🇸

Greenville, North Carolina, United States

Mayfield Brain and Spine

🇺🇸

Cincinnati, Ohio, United States

Allegheny Health Network

🇺🇸

Pittsburgh, Pennsylvania, United States

Brown University Health

🇺🇸

Providence, Rhode Island, United States

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

UT Southwestern Simmons Cancer Center

🇺🇸

Dallas, Texas, United States

Baylor St. Luke's Medical Center | Baylor College of Medicine

🇺🇸

Houston, Texas, United States

Houston Methodist

🇺🇸

Houston, Texas, United States

The University of Texas M. D. Anderson Cancer Center

🇺🇸

Houston, Texas, United States

UT Health San Antonio

🇺🇸

San Antonio, Texas, United States

SCRI with Texas Oncology

🇺🇸

The Woodlands, Texas, United States

Virginia Mason

🇺🇸

Seattle, Washington, United States

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