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

• ClinicalTrials.gov Identifier: NCT04365374
• Recruitment Status: Recruiting
• First Posted: April 28, 2020
• Last Update Posted: January 3, 2023
• Sponsor: GT Medical Technologies, Inc.
• Information provided by (Responsible Party): GT Medical Technologies, Inc.

Tracking Information

• First Submitted Date: April 24, 2020
• First Posted Date: April 28, 2020
• Last Update Posted Date: January 3, 2023
• Actual Study Start Date: April 6, 2021
• Estimated Primary Completion Date: December 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 24, 2020)

Surgical bed recurrence-free survival (SB-RFS) from the time of randomization up to 2 years post radiation. [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 9, 2020)

• Overall Survival [ Time Frame: up to 3 years ]
  Survival of subjects
• Functional Assessment of Cancer Therapy-Brain (FACT-Br) [ Time Frame: up to 9 months ]
  An assessment of quality of life (QOL)
• Linear Analog Scale Assessments (LASA) [ Time Frame: up to 9 months ]
  An assessment of quality of life (QOL)
• Hopkins Verbal Learning Test (HVLT-R) [ Time Frame: up to 24 months ]
  An assessment of neurocognitive status
• Controlled Oral Word Association Test (COWAT) [ Time Frame: up to 24 months ]
  An assessment of neurocognitive status
• Trail Making Tests (TMT) Parts A and B [ Time Frame: up to 24 months ]
  An assessment of neurocognitive status
• Barthel ADL [ Time Frame: up to 24 months ]
  An assessment of physical functioning status

Original Secondary Outcome Measures (submitted: April 24, 2020)

• Overall Survival [ Time Frame: up to 3 years ]
  Survival of subjects
• FACT-Br [ Time Frame: up to 9 months ]
  An assessment of quality of life (QOL)
• LASA [ Time Frame: up to 9 months ]
  An assessment of quality of life (QOL)
• Hopkins Verbal Learning Test (HVLT-R) [ Time Frame: up to 24 months ]
  An assessment of neurocognitive status
• Controlled Oral Word Association Test (COWAT) [ Time Frame: up to 24 months ]
  An assessment of neurocognitive status
• Trail Making Tests (TMT) Parts A and B [ Time Frame: up to 24 months ]
  An assessment of neurocognitive status
• Barthel ADL [ Time Frame: up to 24 months ]
  An assessment of physical functioning status

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Post-Surgical Stereotactic Radiotherapy (SRT) Versus GammaTile-ROADS (Radiation One and Done Study)
• Official Title: A Phase 3 Randomized Controlled Trial of Post-Surgical Stereotactic Radiotherapy (SRT) Versus Surgically Targeted Radiation Therapy (STaRT) With Gamma Tile for Treatment of Newly Diagnosed Metastatic Brain Tumors.
• Brief Summary: This trial will be a randomized controlled study comparing the efficacy and safety of intraoperative radiation therapy using GammaTilesTM (GT) versus SRS 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, 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 GammaTilesTM (GT) versus SRS 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 comparisons 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 and ≥60), duration of extracranial disease control (≤3 months vs >3 months), number of metastases (one or two to four), histology (lung and radiation resistant), and the maximal diameter of the index lesion (≤3 cm and >3 cm).

An index lesion meeting the criteria of 2.5cm to 5cm in diameter and appropriate for gross total resection (GTR), will be identified and up to three other non-resectable 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 SRS) thereby following the standard of care guideline. (NCCN Guidelines, 2019). Additional unresected metastatic lesions will be treated with with stereotactic radiosurgery alone, which also adhears 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 re-resection, and a intense but localized radiation treatment may confer a reduced risk for radiation necrosis compared to other therapies. It is typically easly placed with minimal additional operative time and limited staff radiation exposure.

Given these benefits, the rationale for conducting this randomized control 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Brain Metastases

Intervention

• Device: Gamma Tile-Surgically Targeted Radiation Therapy (STaRT)
  GammaTiles are a permanently implanted radiation device consisting of Cs-131 seeds positioned within a collagen tile
  Other Name: Carrier Tile Brachytherapy Therapy (CTBT)
• Radiation: Stereotactic Radiation Therapy
  External Beam Radiation Therapy

Study Arms

• Experimental: Surgical Resection and GammaTile Therapy
  Surgical Resection and GammaTile Therapy
  Intervention: Device: Gamma Tile-Surgically Targeted Radiation Therapy (STaRT)
• Active Comparator: Surgical Resection and Stereotactic Radiation Therapy
  Surgical Resection and Stereotactic Radiation Therapy
  Intervention: Radiation: Stereotactic Radiation Therapy

• Publications *: Weinberg J. Clinical Trials in Progress: ROADS Trial. Oncology (Williston Park). 2021 Aug 8;35(8):495. doi: 10.46883/ONC.2021.3508.0495.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 24, 2020): 180
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 30, 2027
• Estimated Primary Completion Date: December 30, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 four newly diagnosed brain metastases, identified on the screening MRI, from an extracranial primary tumor.
3. One lesion, designated the index lesion, is planned for surgical resection and is to be between 2.5 cm and 5.0 cm on the screening MRI. Index lesions > 2.0 cm but <2.5 cm are also eligible if surgery is deemed clinically necessary and appropriate for an attempted gross total resection 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 systemic therapies (e.g., chemotherapy, targeted therapeutics, immunotherapy) is 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. KPS score of ≥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 language to allow for completion of neurocognitive tests and completion of QOL questionnaires. Non-English speaking subjects are not permitted to participate given that participation in the real time integrated neurocognitive function tests is mandatory for all patients. 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.

Exclusion Criteria

1. Age <18 years.
2. KPS<70
3. 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.
4. Patients with >4 newly diagnosed metastases on screening MRI
5. Pregnant patients.
6. Primary germ cell tumor, small cell carcinoma, or lymphoma.
7. 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.
8. Prior WBRT for brain metastases.
9. Concomitant therapy that, in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of the study device.
10. 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
11. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Lisa Misell GT Medical Technologies, PhD; (833) 662-0044; lmisell@gtmedtech.com

Contact: Angela Hall GT Medical Technologies, PT; ahall@gtmedtech.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04365374
• Other Study ID Numbers: GTM-102
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: GT Medical Technologies, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: GT Medical Technologies, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jeffrey Weinberg, MD; MD Anderson Cancer Center, Houston, TX

• PRS Account: GT Medical Technologies, Inc.
• Verification Date: December 2022