Clinical trial NCT05222620: SRS Compared With FSRS for Treatment of Intact Metastatic Brain Disease, FRACTIONATE Trial
Official title: Phase IIR Trial of Single Fraction Stereotactic Radiosurgery (SRS) Compared With Fractionated SRS (FSRS) for Intact Metastatic Brain Disease (FRACTIONATE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic Malignant Neoplasm in the Brain
Metastatic Malignant Solid Neoplasm
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2022-02-03
Enrollment: 69
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 phase II trial compares the effect of single fraction stereotactic radiosurgery to fractionated stereotactic radiosurgery for the treatment of patients with cancer that has spread to the brain (metastatic brain disease). Stereotactic radiosurgery (SRS) is a form of radiation therapy that focuses high-power energy on a small area of the body. This trial is being done to determine if single (one) fraction stereotactic radiosurgery is better than fractionated stereotactic radiosurgery or vice versa in controlling tumor and side effects in patients with tumors that have spread to the brain.

Detailed description: PRIMARY OBJECTIVE:

I. To ascertain if the composite endpoint of cumulative treatment failure, defined by time to either local failure or symptomatic radiation brain necrosis of the largest brain metastasis (target lesion), is increased with fractionated stereotactic radiosurgery (FSRS) compared to single fraction stereotactic radiosurgery (SSRS).

SECONDARY OBJECTIVES:

I. To ascertain whether there is improved overall survival in patients who undergo FSRS compared to patients who receive SSRS.

II. To tabulate and descriptively compare the post-treatment adverse events associated with the interventions, including the potential impact of immunotherapy and targeted therapy.

III. To compare rates of radiation necrosis in patients who receive FSRS to patients who receive SSRS.

IV. To evaluate if there is any difference in central nervous system (CNS) failure patterns (e.g. local, distant brain failure) in patients who receive FSRS compared to patients who receive SSRS.

V. To ascertain whether FSRS prolongs time to neurologic death as compared to SRS.

VI. To determine whether there is improved patient reported outcomes (Functional Assessment of Cancer Therapy \[FACT\]-Brain Symptom Index \[FBrSI\]-24) including quality of life for patients who receive FSRS compared to patients who receive SSRS.

VII. To evaluate if there is any difference in CNS failure patterns (e.g. local, distant brain failure) and symptomatic radiation necrosis rates in patients who are treated with gamma knife compared to patients who are treated with a linear accelerator platform.

VIII. To determine whether differences in time to local failure, time to necrosis, or their composite endpoint cumulative treatment failure differs between treatment arms (or other patient or treatment factors) when analyzed on a "per lesion" basis rather than the per patient basis utilized for the primary endpoint.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients undergo single fraction SRS. Patients also undergo magnetic resonance imaging (MRI) at screening and during follow up.

ARM B: Patients undergo fractionated SRS. Patients also undergo MRI at screening and during follow up.

After completion of study treatment, patients are followed up at 3 months, every 3 months for 2 years, and then every 6 months for 3 years.

Eligibility criteria: Inclusion Criteria:

* Age \>= 18 years old
* Presence of presumed brain metastases from an extra-cerebral tumor site (e.g. lung, breast, prostate, etc.)

  * Note: Dural based metastases (e.g. commonly seen in breast cancer) are eligible
* Size of brain metastases

  * At least one intact metastasis (not previously treated with radiosurgery) must measure \>= 2.0 cm and =\< 4.0 cm in maximal extent on the contrasted pre-treatment magnetic resonance imaging (MRI) brain scan obtained =\< 28 days prior to registration
  * If the largest lesion measures \>= 2.0 to =\< 4.0 cm in maximal extent the patient will be randomized
* Able to undergo contrast enhanced MRI brain
* Negative urine or serum pregnancy test completed =\< 7 days prior to registration, for women of childbearing potential only
* Patient willing and able to provide written informed consent
* Karnofsky performance status (KPS) \>= 50
* Eastern Cooperative Oncology Group (ECOG) performance score of (PS) \>= 2
* Past radiosurgery or resection is allowed as long as no definitive evidence of progression in these locations

  * Note: Repeat radiosurgery to the same location/lesion is not allowed on this protocol

Exclusion Criteria:

* Any patient who has received previous whole brain radiation
* Any brain metastasis that is located in the brainstem measuring \>= 2.0 cm in maximal extent
* Any patient with definitive evidence of leptomeningeal metastasis (LMD)

  * NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive cerebrospinal fluid (CSF) cytology and/or unequivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion
* Any patient with an intact brain metastasis measuring \> 4.0 cm

Primary outcomes:
measure: Time to local failure or symptomatic radiation brain necrosis of large brain metastasis
timeFrame: Up to 5 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: From study entry to death from any cause, assessed up to 5 years
measure: Incidence of adverse events
timeFrame: Up to 2 years post radiation therapy
measure: Rates of radiation necrosis
timeFrame: Up to 5 years
measure: Central nervous system (CNS) failure patterns (Fractionation)
timeFrame: Up to 5 years
measure: Time to neurologic death
timeFrame: Up to 5 years
measure: Quality of life (QOL)
timeFrame: Up to 5 years
measure: CNS failure patterns (Gamma Knife)
timeFrame: Up to 5 years
measure: Per lesion analysis between treatment arms: time to local failure
timeFrame: Up to 5 years
measure: Per lesion analysis between treatment arms: time to necrosis
timeFrame: Up to 5 years
measure: Per lesion analysis between treatment arms: endpoint CTF
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Albert Lea
country: United States
facility: Mayo Clinic Health System in Albert Lea
state: Minnesota
city: Mankato
country: United States
facility: Mayo Clinic Health Systems-Mankato
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Eau Claire
country: United States
facility: Mayo Clinic Health System-Eau Claire Clinic
state: Wisconsin
city: La Crosse
country: United States
facility: Mayo Clinic Health System-Franciscan Healthcare
state: Wisconsin
Study officials:
affiliation: Mayo Clinic in Rochester
name: Paul D. Brown, MD
role: PRINCIPAL_INVESTIGATOR
References: