Clinical trial NCT04365374: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Brain Metastases
Keywords: Brain
Tumor
Cancer
New Diagnosis
Metastases
GammaTile
Radiation
Cs-131
Lead sponsor: GT Medical Technologies, Inc.
Sponsor class: INDUSTRY
First posted: 2020-04-28
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Surgical bed recurrence-free survival (SB-RFS) from the time of randomization up to 2 years post radiation.
timeFrame: up to 2 years post-radiation
Secondary outcomes:
measure: Overall Survival
timeFrame: up to 3 years
measure: Functional Assessment of Cancer Therapy-Brain (FACT-Br)
timeFrame: up to 9 months
measure: Linear Analog Scale Assessments (LASA)
timeFrame: up to 9 months
measure: Hopkins Verbal Learning Test (HVLT-R)
timeFrame: up to 24 months
measure: Controlled Oral Word Association Test (COWAT)
timeFrame: up to 24 months
measure: Trail Making Tests (TMT) Parts A and B
timeFrame: up to 24 months
measure: Barthel ADL
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: HonorHeath Scottsdale Osborn Medical Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas Medical Center
state: Arkansas
city: Los Angeles
country: United States
facility: Keck Hospital of Usc
state: California
city: Jacksonville
country: United States
facility: Baptist MD Anderson Cancer Center- Jacksonville
state: Florida
city: Orange Park
country: United States
facility: HCA Florida First Coast Neurology- Orange Park
state: Florida
city: Orlando
country: United States
facility: Advent health Orlando
state: Florida
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Tampa
country: United States
facility: Florida Health Sciences Center, Inc. d/b/a Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Chicago
country: United States
facility: RUSH University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University, IU Health Methodist Hospital
state: Indiana
city: Kansas City
country: United States
facility: The University Of Kansas Cancer Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Detroit
country: United States
facility: Henry Ford Health
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: University Of Minnesota
state: Minnesota
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri
state: Missouri
city: Saint Louis
country: United States
facility: SSM Health Saint Louis University Hospital
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock
state: New Hampshire
city: Neptune
country: United States
facility: HMH Jersey Shore University Medical Center
state: New Jersey
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering
state: New York
city: Westchester
country: United States
facility: Westchester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Health
state: North Carolina
city: Greenville
country: United States
facility: ECU Health
state: North Carolina
city: Cincinnati
country: United States
facility: Mayfield Brain and Spine
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny Health Network
state: Pennsylvania
city: Providence
country: United States
facility: Brown University Health
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Simmons Cancer Center
state: Texas
city: Houston
country: United States
facility: Baylor St. Luke's Medical Center | Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Houston
country: United States
facility: The University of Texas M. D. Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio
state: Texas
city: The Woodlands
country: United States
facility: SCRI with Texas Oncology
state: Texas
city: Seattle
country: United States
facility: Virginia Mason
state: Washington
Study officials:
affiliation: MD Anderson Cancer Center, Houston, TX
name: Jeffrey Weinberg, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Weinberg J. Clinical Trials in Progress: ROADS Trial. Oncology (Williston Park). 2021 Aug 8;35(8):495. doi: 10.46883/ONC.2021.3508.0495.