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Single Fraction Stereotactic Radiosurgery Compared With Fractionated Stereotactic Radiosurgery for Treatment of Intact Metastatic Brain Disease, FRACTIONATE Trial

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ClinicalTrials.gov Identifier: NCT05222620
Recruitment Status : Recruiting
First Posted : February 3, 2022
Last Update Posted : March 16, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

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.

Condition or disease Intervention/treatment Phase
Metastatic Malignant Neoplasm in the Brain Other: Questionnaire Administration Radiation: Stereotactic Radiosurgery Phase 2

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.

ARM B: Patients undergo fractionated SRS.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 69 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase IIR Trial of Single Fraction Stereotactic Radiosurgery (SRS) Compared With Fractionated SRS (FSRS) for Intact Metastatic Brain Disease (FRACTIONATE)
Actual Study Start Date : March 14, 2022
Estimated Primary Completion Date : February 15, 2027
Estimated Study Completion Date : February 15, 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Brain Diseases

Arm Intervention/treatment
Arm A (single fraction SRS)
Patients undergo single fraction SRS.
Other: Questionnaire Administration
Ancillary studies

Radiation: Stereotactic Radiosurgery
Undergo single fraction SRS
Other Names:
  • Stereotactic External Beam Irradiation
  • stereotactic external-beam radiation therapy
  • Stereotactic Radiation Therapy
  • Stereotactic Radiotherapy
  • stereotaxic radiation therapy
  • stereotaxic radiosurgery

Arm B (fractionated SRS)
Patients undergo fractionated SRS.
Other: Questionnaire Administration
Ancillary studies

Radiation: Stereotactic Radiosurgery
Undergo fractionated SRS
Other Names:
  • Stereotactic External Beam Irradiation
  • stereotactic external-beam radiation therapy
  • Stereotactic Radiation Therapy
  • Stereotactic Radiotherapy
  • stereotaxic radiation therapy
  • stereotaxic radiosurgery




Primary Outcome Measures :
  1. Time to local failure or symptomatic radiation brain necrosis of large brain metastasis [ Time Frame: Up to 5 years ]

Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: From study entry to death from any cause, assessed up to 5 years ]
    OS will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms. Medians and 95% confidence intervals will be reported.

  2. Incidence of adverse events [ Time Frame: Up to 2 years post radiation therapy ]
    The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The frequency and percentage of grade 3+ adverse events will be compared between the 2 treatment arms. Comparisons between arms will be made by using either the Chi-square or Fisher's Exact test.

  3. Rates of radiation necrosis [ Time Frame: Up to 5 years ]
    Will compare rates of radiation necrosis in patients who receive fractionated stereotactic radiosurgery (FSRS) to patients who receive single fraction stereotactic radiosurgery (SSRS). Comparisons between arms will be made by using either the Chi-square or Fisher's Exact test.

  4. Central nervous system (CNS) failure patterns (Fractionation) [ Time Frame: Up to 5 years ]
    Will evaluate if there is any difference in CNS failure patterns (e.g. local, distant brain failure) in patients who receive FSRS compared to patients who receive SSRS. Comparisons between arms will be made by using either the Chi-square or Fisher's Exact test.

  5. Time to neurologic death [ Time Frame: Up to 5 years ]
    Will ascertain whether FSRS prolongs time to neurologic death as compared to SSRS. This will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms. Medians and 95% confidence intervals will be reported.

  6. Quality of life (QOL) [ Time Frame: Up to 5 years ]
    Will determine whether there are 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. Changes over time in QOL from baseline will be compared between arms using the 2-sample t-test (or Wilcoxon Rank-Sum test for non-normal data). Box-plots will be used to show differences between arms graphically.

  7. CNS failure patterns (Gamma Knife) [ Time Frame: Up to 5 years ]
    Will 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. Comparisons between arms will be made by using either the Chi-square or Fisher's Exact test.

  8. Per lesion analysis between treatment arms [ Time Frame: Up to 5 years ]
    Will determine whether differences in time to local 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. Time-to-event models (Cox and Kaplan- Meier) with sandwich estimators for covariance will be utilized to in treatment comparisons, with model comparisons completed through log-likelihood and Akaike Information Criterion.

  9. Per lesion analysis between treatment arms [ Time Frame: Up to 5 years ]
    Will determine whether differences in time to necrosis 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. Time-to-event models (Cox and Kaplan- Meier) with sandwich estimators for covariance will be utilized to in treatment comparisons, with model comparisons completed through log-likelihood and Akaike Information Criterion.

  10. Per lesion analysis between treatment arms [ Time Frame: Up to 5 years ]
    Will determine whether differences in the composite endpoint CTF 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. Time-to-event models (Cox and Kaplan- Meier) with sandwich estimators for covariance will be utilized to in treatment comparisons, with model comparisons completed through log-likelihood and Akaike Information Criterion.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05222620


Locations
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United States, Minnesota
Mayo Clinic in Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Office    855-776-0015    mayocliniccancerstudies@mayo.edu   
Principal Investigator: Paul D. Brown, M.D.         
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Paul D Brown Mayo Clinic in Rochester
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Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT05222620    
Other Study ID Numbers: GMROR2163
NCI-2021-14230 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
GMROR2163 ( Other Identifier: Mayo Clinic in Rochester )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: February 3, 2022    Key Record Dates
Last Update Posted: March 16, 2022
Last Verified: March 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases