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Trial record 1 of 1 for:    A071801
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Single Fraction Stereotactic Radiosurgery Compared With Fractionated Stereotactic Radiosurgery in Treating Patients With Resected Metastatic Brain Disease

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ClinicalTrials.gov Identifier: NCT04114981
Recruitment Status : Recruiting
First Posted : October 3, 2019
Last Update Posted : February 5, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Tracking Information
First Submitted Date  ICMJE October 2, 2019
First Posted Date  ICMJE October 3, 2019
Last Update Posted Date February 5, 2020
Actual Study Start Date  ICMJE October 11, 2019
Estimated Primary Completion Date March 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 2, 2019)
Surgical bed recurrence-free survival (SB-RFS) [ Time Frame: From the time of randomization up to 2 years post radiation ]
Surgical bed control is defined as the absence of new nodular contrast enhancement in the surgical bed. In other words, a surgical bed recurrence-free survival (SB-RFS) event is defined as radiographic evidence of a new contrast-enhancing lesion (specifically any new progressive enhancing nodularity) at the site of the surgical resection. Will use a stratified log-rank test that compares and will report the median SB-RFS times between the single fraction stereotactic radiosurgery (SSRS) and fractionated stereotactic radiosurgery (FSRS) arms while adjusting for the stratification factors.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT04114981 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 2, 2019)
  • Change in Functional Assessment of Cancer Therapy-Brain (FACT-BR) Emotional sub-scale score [ Time Frame: At 9 months ]
    The average change from baseline to 9 months in the Functional Assessment of Cancer Therapy-Brain (FACT-BR) Emotional sub-scale will be compared between randomization arms.
  • Functional Assessment of Cancer Therapy-Brain (FACT-BR) total score [ Time Frame: At 9 months ]
    The average change from baseline to 9 months in the Functional Assessment of Cancer Therapy-Brain (FACT-BR) total score will be compared between randomization arms.
  • Linear Analog Self-Assessment (LASA) overall quality of life [ Time Frame: At 9 months ]
    The average change from baseline to 9 months in the Linear Analog Self-Assessment (LASA) overall total score will be compared between randomization arms.
  • Functional Assessment of Cancer Therapy-Brain (FACT-BR) Emotional sub-scale score for long-term survivors [ Time Frame: At 12 months ]
    Long-term survivors defined as patients who are alive more than 12 months from time of randomization. The average change from baseline to 12 months in the Functional Assessment of Cancer Therapy-Brain (FACT-BR) Emotional sub-scale for the long-term survivors will be compared between randomization arms.
  • Functional Assessment of Cancer Therapy-Brain (FACT-BR) total score for long-term survivors [ Time Frame: At 12 months ]
    Long-term survivors defined as patients who are alive more than 12 months from time of randomization. The average change from baseline to 12 months in the Functional Assessment of Cancer Therapy-Brain (FACT-BR) total score for the long-term survivors will be compared between randomization arms.
  • Linear Analog Self-Assessment (LASA) overall quality of life for long-term survivors [ Time Frame: At 12 months ]
    Long-term survivors defined as patients who are alive more than 12 months from time of randomization. The average change from baseline to 9 months in the Linear Analog Self-Assessment (LASA) overall total score for the long-term survivors will be compared between randomization arms.
  • Karnofsky Performance Status (KPS) [ Time Frame: Up to 24 months ]
    The duration of Karnofsky Performance Status (KPS) functional independence will be the time to when the KPS scores per patient decrease below their baseline level and will be compared between treatment arms by the logrank test. Median durations of KPS functional independence will be reported and compared between randomization arms.
  • Barthel Activities of Daily Living (ADL) Index [ Time Frame: Up to 24 months ]
    The duration of Barthel Activities of Daily Living (ADL) functional independence will be the time to when the ADL scores per patient decrease below their baseline level and will be compared between treatment arms by the logrank test. Median durations of ADL functional independence will be reported and compared between randomization arms.
  • Karnofsky Performance Status (KPS) for long-term survivors [ Time Frame: Up to 24 months ]
    Long-term survivors defined as patients who are alive more than 12 months from time of randomization. The duration of Karnofsky Performance Status (KPS) functional independence will be the time to when the KPS scores per patient decrease below their baseline level and will be compared between treatment arms by the logrank test. Median durations of KPS functional independence for long-term survivors will be reported and compared between randomization arms.
  • Barthel Activities of Daily Living (ADL) Index for long-term survivors [ Time Frame: Up to 24 months ]
    Long-term survivors defined as patients who are alive more than 12 months from time of randomization. The duration of Barthel Activities of Daily Living (ADL) functional independence will be the time to when the ADL scores per patient decrease below their baseline level and will be compared between treatment arms by the logrank test. Median durations of ADL functional independence for long-term survivors will be reported and compared between randomization arms.
  • Overall survival [ Time Frame: Up to 5 years ]
    Overall survival time will be compared between the treatment arms using a stratified log-rank test. If the proportional hazards assumption is violated, a restricted means analysis will be used to compare overall survival between the two treatment arms. Median survival times per treatment arms will be reported.
  • Incidence of adverse events [ Time Frame: Up to 24 months ]
    The Common Terminology Criteria for Adverse Events version 5.0 will be used. The proportion of patients experiencing any adverse event will be compared between the two treatment arms using a chi-square (or Fisher's exact test, if more appropriate).
  • Proportion of patients with radiation necrosis [ Time Frame: At 24 months ]
    The proportion of patients with radiation necrosis within 24 months from of starting treatment will be compared between the treatment arms with a chi-square test (or Fisher's exact test if more appropriate).
  • Time until whole-brain radiotherapy (WBRT) due to any reason (e.g. surgical bed recurrence, recurrence/progression at another central nervous system [CNS] site) [ Time Frame: Up to 24 months ]
    Time until whole-brain radiotherapy (WBRT) will be compared between the treatment arms using a stratified log-rank test. Median time until WBRT per treatment arms will be reported.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Single Fraction Stereotactic Radiosurgery Compared With Fractionated Stereotactic Radiosurgery in Treating Patients With Resected Metastatic Brain Disease
Official Title  ICMJE Phase III Trial of Post-Surgical Single Fraction Stereotactic Radiosurgery (SRS) Compared With Fractionated SRS for Resected Metastatic Brain Disease
Brief Summary This phase III trial studies how well single fraction stereotactic radiosurgery works compared with fractionated stereotactic radiosurgery in treating patients with cancer that has spread to the brain from other parts of the body and has been removed by surgery. Single fraction stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Fractionated stereotactic radiosurgery delivers multiple, smaller doses of radiation therapy over time. This study may help doctors find out if fractionated stereotactic radiosurgery is better or worse than the usual approach with single fraction stereotactic radiosurgery.
Detailed Description

PRIMARY OBJECTIVES:

I. To ascertain if time to surgical bed failure is increased with fractionated stereotactic radiosurgery (FSRS) compared to single-fraction stereotactic radiosurgery (SSRS) in patients with resected brain metastasis.

SECONDARY OBJECTIVES:

I. To ascertain if there is better emotional well-being at 9 months as assessed by the Functional Assessment of Cancer Therapy-Brain (FACT-BR) in patients with resected brain metastasis undergoing FSRS compared to SSRS (Primary quality of life [QOL] objective).

II. To ascertain whether there is improved overall survival in patients with resected brain metastases who undergo FSRS compared to patients who receive SSRS.

III. To ascertain in patients with resected brain metastases whether there is improved overall QOL as assessed by the FACT-BR and Linear Analog Self-Assessment (LASA) in patients who receive FSRS compared to patients who receive SSRS (Secondary QOL objective).

IV. To compare the functional independence in patients who receive FSRS to patients who receive SSRS.

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

VI. To compare rates of radiation necrosis at 12 months in patients who receive FSRS to patients who receive SSRS.

VII. To evaluate if there is any difference in central nervous system (CNS) failure patterns (local, distant brain failure, local leptomeningeal disease, widespread leptomeningeal disease) in patients who receive FSRS compared to patients who receive SSRS after resection of brain metastasis.

VIII. To ascertain in patients with resected brain metastases whether there is increased time to whole-brain radiotherapy (WBRT) in patients who receive FSRS compared to patients who receive SSRS.

IX. To determine in long-term survivors (patients who are alive more than 12 months from time of randomization) whether there is better emotional well-being and overall QOL as assessed by the FACT-BR and LASA in patients who receive FSRS to the surgical bed compared to patients who receive SSRS (Secondary QOL objective).

X. To ascertain if time to surgical bed failure as assessed by central review is increased with FSRS compared to SSRS in patients with resected brain metastasis.

XI. To ascertain in patients with resected brain metastases whether there is improved QOL as assessed by all other total and individual FACT-BR and LASA items and subscale values in patients who receive FSRS compared to patients who receive SSRS (Exploratory QOL objective).

XII. To determine in patients with resected brain metastases whether there is less cognitive progression in patients who receive FSRS to the surgical bed compared to patients who receive SSRS (Exploratory cognitive objective).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo SSRS over 1 session.

ARM II: Patients undergo FSRS over 3 or 5 daily sessions.

After completion of study, patients are followed up at 30 days, at 3, 6, 9, 12, 16, and 24 months, then every 6 months until 5 years from randomization.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Malignant Neoplasm in the Brain
Intervention  ICMJE
  • Radiation: Single Fraction Stereotactic Radiosurgery
    Undergo SSRS
    Other Name: Stereotactic Radiosurgery
  • Radiation: Fractionated Stereotactic Radiosurgery
    Undergo FSRS
    Other Name: Stereotactic Radiosurgery
  • Procedure: Quality-of-Life Assessment
    Ancillary studies
  • Other: Questionnaire Administration
    Ancillary studies
Study Arms  ICMJE
  • Active Comparator: Arm I (SSRS)
    Patients undergo SSRS over 1 session.
    Interventions:
    • Radiation: Single Fraction Stereotactic Radiosurgery
    • Procedure: Quality-of-Life Assessment
    • Other: Questionnaire Administration
  • Experimental: Arm II (FSRS)
    Patients undergo FSRS over 3 or 5 daily sessions.
    Interventions:
    • Radiation: Fractionated Stereotactic Radiosurgery
    • Procedure: Quality-of-Life Assessment
    • Other: Questionnaire Administration
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 2, 2019)
208
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2028
Estimated Primary Completion Date March 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

PRE-REGISTRATION:

  • Pathology from the resected brain metastasis must be consistent with a non-central nervous system primary site. Patients with or without active disease outside the nervous system are eligible (including patients with unknown primaries), as long as the pathology from the brain is consistent with a non-central nervous system primary site.
  • Three or fewer (i.e. 0 to 3) unresected brain metastases (as defined on the post operative magnetic resonance imaging [MRI]) at the time of screening.

    o Note: Dural based metastases (e.g. commonly seen in breast cancer) are eligible.

  • Unresected lesions must measure < 4.0 cm in maximal extent on the contrasted post-operative treatment MRI brain scan. The unresected lesions will be treated with SRS as outlined in the treatment section of the concept.

    o Note: The metastases size restriction does not apply to the resected brain metastasis.

  • One brain metastasis must be completely (gross total resection) resected =< 30 days prior to pre-registration.

    o NOTE: May not have had resection of more than one brain metastasis.

  • The resected brain metastasis must measure 2 cm or larger on the pre-operative MRI.
  • Resection cavity must measure < 5.0 cm in maximal extent and the resection must be complete (gross total resection) on the post-operative MRI obtained =< 30 days prior to pre-registration.
  • Karnofsky performance status of >= 60.
  • For women of childbearing potential only, a negative urine or serum pregnancy test done =< 7 days prior to pre-registration is required.

    • 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.
    • A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
  • Ability to complete an MRI of the head with contrast.
  • The brain metastasis must be located > 5 mm of the optic chiasm and outside the brain stem.
  • Must not have any prior whole brain radiation therapy.
  • Past radiosurgery to other lesions is allowed.

    o NOTE: The surgically resected lesion cannot be the same location treated in the past with radiosurgery (i.e. repeat radiosurgery to the same location/lesion is not allowed on this protocol).

  • May not have primary germ cell tumor, small cell carcinoma, or lymphoma.
  • No evidence of leptomeningeal metastasis (LMD).

    o NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive cerebrospinal fluid (CSF) cytology and/or equivocal 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.

  • Must be fluent in English, Spanish, or French.

REGISTRATION:

• Completion of all baseline electronic patient-reported outcome (ePRO) quality of life measures (or booklet quality of life measures) and Montreal Cognitive Assessment (MoCA).

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Paul D. Brown, MD 507-284-3551 brown.paul@mayo.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04114981
Other Study ID Numbers  ICMJE A071801
NCI-2019-02394 ( Registry Identifier: NCI Clinical Trial Reporting Program )
U10CA180821 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party Alliance for Clinical Trials in Oncology
Study Sponsor  ICMJE Alliance for Clinical Trials in Oncology
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Paul D. Brown, MD Mayo Clinic
PRS Account Alliance for Clinical Trials in Oncology
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP