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A Study of Whole Brain Radiation Therapy and Capecitabine in Breast Cancer Participants With Newly Diagnosed Brain Metastasis (XERAD)

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ClinicalTrials.gov Identifier: NCT00977379
Recruitment Status : Terminated (Due to an insufficient number of participants enrolled.)
First Posted : September 15, 2009
Results First Posted : November 15, 2016
Last Update Posted : November 15, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE September 14, 2009
First Posted Date  ICMJE September 15, 2009
Results First Submitted Date  ICMJE September 26, 2016
Results First Posted Date  ICMJE November 15, 2016
Last Update Posted Date November 15, 2016
Study Start Date  ICMJE August 2009
Actual Primary Completion Date February 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 26, 2016)
  • Percentage of Participants With Best Objective Central Nervous System (CNS) Response, Assessed by Centralized Independent Expert According to Magnetic Resonance Imaging (MRI) - Intent-to-Treat (ITT) Population [ Time Frame: Baseline until disease progression (PD), unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first (up to approximately 1 year 5.5 months overall) ]
    Best objective CNS response was defined as having complete response (CR) or partial response (PR) for CNS metastasis, assessed by contrast-enhanced MRI using response evaluation criteria in solid tumors (RECIST). CR: disappearance of all CNS lesions. PR: greater than or equal to (>/=) 30 percent (%) decrease in sum of longest diameters (LD) of CNS lesions taking as reference the baseline sum LD.
  • Percentage of Participants With Best Objective CNS Response, Assessed by Centralized Independent Expert According to MRI - Per-Protocol (PP) Population [ Time Frame: Baseline until PD, unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first (up to approximately 1 year 5.5 months overall) ]
    Best objective CNS response was defined as having CR or PR for CNS metastasis, assessed by contrast-enhanced MRI using RECIST. CR: disappearance of all CNS lesions. PR: >/=30% decrease in sum of LD of CNS lesions taking as reference the baseline sum LD.
Original Primary Outcome Measures  ICMJE
 (submitted: September 14, 2009)
Best objective CNS response (CR+PR) assessed by contrast-enhanced MRI reviewed by centralized independent expert [ Time Frame: MRI 6 weeks after 1st day of radiotherapy and every 9 weeks thereafter ]
Change History Complete list of historical versions of study NCT00977379 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2016)
  • Percentage of Participants With Objective CNS Response at 4 Weeks After Completion of WBRT, Assessed by Centralized Independent Expert According to MRI [ Time Frame: Baseline until PD, unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first up to 4 weeks after completion of WBRT (up to approximately 7 weeks) ]
    Objective CNS response was defined as having CR or PR for CNS metastasis, assessed by contrast-enhanced MRI using RECIST. CR: disappearance of all CNS lesions. PR: >/=30% decrease in sum of LD of CNS lesions taking as reference the baseline sum LD.
  • Percentage of Participants With Best Objective CNS Response, Assessed by Investigator According to MRI [ Time Frame: Baseline until PD, unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first (up to approximately 1 year 5.5 months overall) ]
    Best objective CNS response was defined as having CR or PR for CNS metastasis, assessed by contrast-enhanced MRI using RECIST. CR: disappearance of all CNS lesions. PR: >/=30% decrease in sum of LD of CNS lesions taking as reference the baseline sum LD.
  • Percentage of Participants With Objective CNS Response at 4 Weeks After Completion of WBRT, Assessed by Centralized Independent Expert According to MRI in 3 Dimension [ Time Frame: Baseline until PD, unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first up to 4 weeks after completion of WBRT (up to approximately 7 weeks) ]
    Objective CNS response was defined as having CR or PR for CNS metastasis, assessed by 3 dimensional MRI using RECIST. CR: disappearance of all CNS lesions. PR: >/=30% decrease in sum of LD of CNS lesions taking as reference the baseline sum LD.
  • Percentage of Participants With Clinical Benefit, Assessed by Investigator According to MRI [ Time Frame: Baseline until PD, unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first (up to approximately 1 year 5.5 months overall) ]
    Clinical benefit was defined as having CR, PR, or stable disease (SD), assessed by contrast-enhanced MRI using RECIST. CR: disappearance of all CNS lesions. PR: >/=30 % decrease in sum of LD of CNS lesions taking as reference the baseline sum LD. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) taking as reference smallest sum LD since treatment started. PD: a 20% or greater increase in the sum of the LD of CNS lesions taking as reference the smallest sum LD recorded since the treatment started or appearance of one or more CNS lesions and/or unequivocal progression of existing CNS lesions.
  • Percentage of Participants With Objective CNS Response at 4 Weeks After Completion of WBRT, Assessed by Investigator According to MRI [ Time Frame: Baseline until PD, unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first up to 4 weeks after completion of WBRT (up to approximately 7 weeks) ]
    Objective CNS response was defined as having CR or PR for CNS metastasis, assessed by contrast-enhanced MRI using RECIST. CR: disappearance of all CNS lesions. PR: >/=30 % decrease in sum of LD of CNS lesions taking as reference the baseline sum LD.
  • Duration of CNS Response, Assessed by Investigator According to MRI [ Time Frame: Baseline until PD, unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first (up to approximately 1 year 5.5 months overall) ]
    Duration of CNS response was defined as the time from first documented cranial CR or PR (whichever was recorded first) until the first date CNS recurrence or progression was documented as assessed by contrast-enhanced MRI according to RECIST criteria but without exam for response confirmation. CR: disappearance of all CNS lesions. PR: >/=30 % decrease in sum of LD of CNS lesions taking as reference the baseline sum LD. PD: a 20% or greater increase in the sum of the LD of CNS lesions taking as reference the smallest sum LD recorded since the treatment started or appearance of one or more CNS lesions and/or unequivocal progression of existing CNS lesions.
  • Time to CNS Progression, Assessed by Investigator According to MRI [ Time Frame: Baseline until PD, unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first (up to approximately 1 year 5.5 months overall) ]
    Time to CNS progression was defined as the time from start of study treatment to first documentation of PD or death due to CNS metastasis. PD was assessed by contrast-enhanced MRI according to RECIST. PD: a 20% or greater increase in the sum of the LD of CNS lesions taking as reference the smallest sum LD recorded since the treatment started or appearance of one or more CNS lesions and/or unequivocal progression of existing CNS lesions.
  • Percentage of Participants With Best Objective Extra-cranial Disease Response, Assessed by Investigator According to Computed Tomography (CT) [ Time Frame: Baseline until PD, unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first (up to approximately 1 year 5.5 months overall) ]
    Best objective extra-cranial response was defined as having CR or PR for extra-cranial lesions, assessed by CT using RECIST. CR: disappearance of all extra-cranial lesions. PR: >/=30 % decrease in sum of LD of extra-cranial lesions taking as reference the baseline sum LD.
  • Percentage of Participants With Objective Extra-cranial Disease Response at 4 Weeks After Completion of WBRT, Assessed by Investigator According to CT [ Time Frame: Baseline until PD, unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first up to 4 weeks after completion of WBRT (up to approximately 7 weeks) ]
    Objective extra-cranial response was defined as having CR or PR for extra-cranial lesions, assessed by CT using RECIST. CR: disappearance of all extra-cranial lesions. PR: >/=30 % decrease in sum of LD of extra-cranial lesions taking as reference the baseline sum LD.
  • Time to Extra-cranial Disease Progression, Assessed by Investigator According to CT [ Time Frame: Baseline until PD, unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first (up to approximately 1 year 5.5 months overall) ]
    Time to extra-cranial progression was defined as the time from start of study treatment to first documentation of PD or death due to extra-cranial lesions. PD was assessed by CT according to RECIST. PD: a 20% or greater increase in the sum of the LD of extra-cranial lesions taking as reference the smallest sum LD recorded since the treatment started or appearance of one or more extra-cranial lesions and/or unequivocal progression of existing extra-cranial lesions.
  • Time to Progression, Assessed by Investigator According to MRI and CT [ Time Frame: Baseline until PD, unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first (up to approximately 1 year 5.5 months overall) ]
    Time to progression was defined as the time from start of study treatment to first documentation of PD or death due to tumor (CNS or extra-cranial). PD was assessed by MRI or CT according to RECIST. PD: a 20% or greater increase in the sum of the LD of CNS or extra-cranial lesions taking as reference the smallest sum LD recorded since the treatment started or appearance of one or more CNS or extra-cranial lesions and/or unequivocal progression of existing CNS or extra-cranial lesions.
  • Overall Survival (OS) [ Time Frame: Baseline until death (up to approximately 1 year 5.5 months overall) ]
    OS was defined as the time from the start of study treatment to date of death due to any cause. OS was assessed using Kaplan-Meier analysis.
  • Absolute Change From Baseline in Mini Mental State (MMS) Total Score [ Time Frame: Baseline, Up to end of Treatment (up to 10.6 months overall) ]
    MMS was an 11-question measure that tested five areas of cognitive function: orientation, registration, attention and calculation, recall, and language. Four items were scored on a scale of 0 to 1; 1 item was scored on a scale of 0 to 2; 3 items were scored on a scale of 0 to 3; and 3 items were scored on a scale of 0 to 5. MMS total score was obtained by adding the scores of all individual items and ranged from 0 to 30, where higher scores indicate better cognitive state.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2009)
  • Objective CNS response (CR+PR) assessed by MRI 4 weeks after completion of WBRT [ Time Frame: 6 weeks after 1st day of radiotherapy ]
  • Best objective CNS response (CR+PR), clinical benefit (CR+PR+stable disease), duration of CNS response, brain progression-free survival [ Time Frame: assessed 6 weeks after 1st day of radiotherapy and every 9 weeks thereafter or at time of clinical deterioration ]
  • Extracranial disease response rate according to RECIST criteria [ Time Frame: assessed after 6 weeks and every 9 weeks thereafter ]
  • progression-free survival (CNS or extracranial), overall survival [ Time Frame: assessed every 9 weeks or at time of clinical deterioration and by the end of the study ]
  • Safety, AEs [ Time Frame: throughout study, laboratory and neurological assessments every 3 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Whole Brain Radiation Therapy and Capecitabine in Breast Cancer Participants With Newly Diagnosed Brain Metastasis
Official Title  ICMJE XERAD: Open-Label, Phase II, Randomized, Comparative, Multicentre Trial of Concurrent Whole Brain Radiation Therapy (WBRT) and Capecitabine (Xeloda®) Followed by Maintenance Capecitabine Compared With Standard WBRT in Breast Cancer Patients With Newly Diagnosed Brain Metastasis
Brief Summary This open-label, randomized, parallel arm study will evaluate the effect of capecitabine administered concurrently with WBRT and as maintenance therapy in participants with breast cancer and newly diagnosed brain metastases. Participants will be randomized to receive either capecitabine with 10 days standard WBRT, or WBRT alone. Maintenance therapy will follow with capecitabine or another systemic therapy in the WBRT only group.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Radiation: WBRT
    3000 cGy WBRT in 10 single daily fractions over 12 to 14 days (300 cGy / fraction).
  • Drug: Capecitabine
    825 mg/m^2 orally twice daily, Days 1-14 of a 21 day cycle for 1 cycle followed by 1000 mg/m^2 orally twice daily Days 1-14 every 21 days starting with Cycle 2.
    Other Name: Xeloda
  • Drug: Standard of Care
    The choice of standard of care will be at the discretion of the treating oncologist. The protocol does not specify any particular standard of care treatment.
Study Arms  ICMJE
  • Active Comparator: WBRT Followed by Standard of Care
    Participants will receive 3000 centi-Gray (cGy) WBRT in 10 single daily fractions over 12 to 14 days (300 cGy / fraction) followed by standard of care therapy at the discretion of the treating oncologist starting no earlier than 2 weeks after completion of WBRT. The participants will be followed during the treatment until the halting of standard of care for any reason (central nervous system [CNS] or extra-cranial tumor progression, unacceptable toxicity, change of therapeutic strategy, withdrawal of participant consent, or death).
    Interventions:
    • Radiation: WBRT
    • Drug: Standard of Care
  • Experimental: WBRT+Capecitabine Followed by Capecitabine Maintenance
    Participants will receive 3000 cGy WBRT in 10 single daily fractions over 12 to 14 days (300 cGy / fraction) concurrent with capecitabine 825 milligrams per square meter (mg/m^2) orally twice daily, Days 1-14 of a 21 day cycle for 1 cycle followed by capecitabine 1000 mg/m^2 orally twice daily Days 1-14 every 21 days starting with Cycle 2, one week after completion of WBRT and continuing until the halting of capecitabine for any reason (CNS or extra-cranial progression, unacceptable toxicity, withdrawal of participant consent or death).
    Interventions:
    • Radiation: WBRT
    • Drug: Capecitabine
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 Terminated
Actual Enrollment  ICMJE
 (submitted: November 15, 2011)
24
Original Estimated Enrollment  ICMJE
 (submitted: September 14, 2009)
130
Actual Study Completion Date  ICMJE February 2011
Actual Primary Completion Date February 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Women with histologically confirmed breast cancer with known human epidermal receptor-2 (HER2) and hormone status
  • Newly diagnosed CNS metastasis with at least one brain lesion measuring greater than or equal to (>/=) 1 centimeter (cm) or two lesions measuring >/= 0.5 to less than (<) 1 cm in longest dimension
  • Participant not eligible for or refusing surgery or stereotactic radiosurgery
  • Eastern cooperative oncology group (EOCG) performance status 0 to 2

Exclusion Criteria:

  • Prior treatment of brain metastases
  • Leptomeningeal disease
  • Known contra-indication to radiotherapy or magnetic resonance imaging (MRI) or capecitabine
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00977379
Other Study ID Numbers  ICMJE ML21873
2008-007349-30
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date September 2016

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