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)

Overview

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, for 3-5 treatments, given over no more than 8 days. 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.

Interventions

• Other Questionnaire Administration
  Ancillary studies
• Radiation Stereotactic Radiosurgery
  Undergo single fraction SRS
• Radiation Stereotactic Radiosurgery
  Undergo fractionated SRS
• Procedure Magnetic Resonance Imaging
  Undergo MRI

Primary outcome measures

• Time to local failure or symptomatic radiation brain necrosis of large brain metastasis [Time frame: Up to 5 years]

Secondary outcome measures (10)

• Overall survival (OS) [Time frame: From study entry to death from any cause, assessed up to 5 years]
• Incidence of adverse events [Time frame: Up to 2 years post radiation therapy]
• Rates of radiation necrosis [Time frame: Up to 5 years]
• Central nervous system (CNS) failure patterns (Fractionation) [Time frame: Up to 5 years]
• Time to neurologic death [Time frame: Up to 5 years]
• Quality of life (QOL) [Time frame: Up to 5 years]
• CNS failure patterns (Gamma Knife) [Time frame: Up to 5 years]
• Per lesion analysis between treatment arms: time to local failure [Time frame: Up to 5 years]
• Per lesion analysis between treatment arms: time to necrosis [Time frame: Up to 5 years]
• Per lesion analysis between treatment arms: endpoint CTF [Time frame: Up to 5 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 is willing and able to provide written informed consent or have a legally Authorized Representative (LAR) who is responsible for the care and well-being of the potential study participant provide 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 7 centers

• Mayo Clinic in Arizona — Scottsdale
• Mayo Clinic in Florida — Jacksonville
• Mayo Clinic Health System in Albert Lea — Albert Lea
• Mayo Clinic Health Systems-Mankato — Mankato
• Mayo Clinic in Rochester — Rochester
• Mayo Clinic Health System-Eau Claire Clinic — Eau Claire
• Mayo Clinic Health System-Franciscan Healthcare — La Crosse

Identifiers

NCT: NCT05222620 · GMROR2163 · NCI-2021-14230 · 21-003768

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗