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.
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Brain Metastases
- Sponsor
- GT Medical Technologies, Inc.
- Enrollment
- 230
- Locations
- 37
- Primary Endpoint
- Surgical bed recurrence-free survival (SB-RFS) from the time of randomization up to 2 years post radiation.
- Status
- Active, not recruiting
- Last Updated
- 6 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •One to six newly diagnosed brain metastases, identified on the screening MRI, from an extracranial primary tumor.
- •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.
- •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.
- •All metastases must be located ≥ 5 mm from the optic chiasm and outside the brainstem. Dural based metastasis are eligible.
- •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.
- •Karnofsky Performance Scale (KPS) score of ≥
- •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 ≥
- •Stable systemic disease or reasonable systemic treatment options predicting a life expectancy of ≥6 months.
- •Ability to complete an MRI of the head with contrast
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Overall Survival(up to 3 years)
- Hopkins Verbal Learning Test (HVLT-R)(up to 24 months)
- Controlled Oral Word Association Test (COWAT)(up to 24 months)
- Trail Making Tests (TMT) Parts A and B(up to 24 months)
- Barthel ADL(up to 24 months)
- Functional Assessment of Cancer Therapy-Brain (FACT-Br)(up to 9 months)
- Linear Analog Scale Assessments (LASA)(up to 9 months)