Breast Cancer
Conditions
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.
Interventions
RADIATIONWBRT
3000 cGy WBRT in 10 single daily fractions over 12 to 14 days (300 cGy / fraction).
DRUGCapecitabine
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.
DRUGStandard 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.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | 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 | 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 | 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 | 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 Objective CNS Response at 4 Weeks After Completion of WBRT, Assessed by Centralized Independent Expert According to MRI | 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 Extra-cranial Disease Response, Assessed by Investigator According to Computed Tomography (CT) | 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 | 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 | 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 | 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. |
| Absolute Change From Baseline in Mini Mental State (MMS) Total Score | 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. |
| Overall Survival (OS) | 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. |
| Percentage of Participants With Best Objective CNS Response, Assessed by Investigator According to MRI | 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. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| WBRT Followed by Standard of Care Participants received 3000 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 were followed during the treatment until the halting of standard of care for any reason (CNS or extra-cranial tumor progression, unacceptable toxicity, change of therapeutic strategy, withdrawal of participant consent, or death). | 12 |
| WBRT+Capecitabine Followed by Capecitabine Maintenance Participants received 3000 cGy WBRT in 10 single daily fractions over 12 to 14 days (300 cGy / fraction) concurrent with capecitabine 825 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). | 11 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 7 | 9 |
| Overall Study | Participant Moving House | 0 | 1 |
| Overall Study | Premature Study Termination | 4 | 0 |
| Overall Study | Randomization Error | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | WBRT Followed by Standard of Care | WBRT+Capecitabine Followed by Capecitabine Maintenance | Total |
|---|---|---|---|
| Age, Continuous | 54.8 years STANDARD_DEVIATION 15.6 | 57.8 years STANDARD_DEVIATION 13.1 | 56.2 years STANDARD_DEVIATION 14.2 |
| Sex: Female, Male Female | 12 Participants | 11 Participants | 23 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 12 | 10 / 11 |
| serious Total, serious adverse events | 6 / 12 | 6 / 11 |
Outcome results
Primary
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
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.
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)
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| WBRT Followed by Standard of Care | 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 | 25.0 percentage of participants |
| WBRT+Capecitabine Followed by Capecitabine Maintenance | 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 | 36.4 percentage of participants |
Primary
Percentage of Participants With Best Objective CNS Response, Assessed by Centralized Independent Expert According to MRI - Per-Protocol (PP) Population
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.
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)
Population: PP population included all ITT population participants excluding participants with following major protocol violations: inclusion and exclusion criteria not met; intake of prohibited treatment, protocol design and/or visit dates not respected; and missing values for main criterion without premature withdrawal.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| WBRT Followed by Standard of Care | Percentage of Participants With Best Objective CNS Response, Assessed by Centralized Independent Expert According to MRI - Per-Protocol (PP) Population | 20.0 percentage of participants |
| WBRT+Capecitabine Followed by Capecitabine Maintenance | Percentage of Participants With Best Objective CNS Response, Assessed by Centralized Independent Expert According to MRI - Per-Protocol (PP) Population | 33.3 percentage of participants |
Secondary
Absolute Change From Baseline in Mini Mental State (MMS) Total Score
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.
Time frame: Baseline, Up to end of Treatment (up to 10.6 months overall)
Population: ITT population. Here, number of participants analyzed = participants evaluable for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| WBRT Followed by Standard of Care | Absolute Change From Baseline in Mini Mental State (MMS) Total Score | -1.5 units on a scale | Standard Deviation 4.3 |
| WBRT+Capecitabine Followed by Capecitabine Maintenance | Absolute Change From Baseline in Mini Mental State (MMS) Total Score | 0.9 units on a scale | Standard Deviation 3.2 |
Secondary
Duration of CNS Response, Assessed by Investigator According to MRI
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 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)
Population: ITT population. Here, number of participants analyzed = participants having had a CR or PR during the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| WBRT Followed by Standard of Care | Duration of CNS Response, Assessed by Investigator According to MRI | 6.2 months |
| WBRT+Capecitabine Followed by Capecitabine Maintenance | Duration of CNS Response, Assessed by Investigator According to MRI | 2.6 months |
Secondary
Overall Survival (OS)
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.
Time frame: Baseline until death (up to approximately 1 year 5.5 months overall)
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| WBRT Followed by Standard of Care | Overall Survival (OS) | 9.8 months |
| WBRT+Capecitabine Followed by Capecitabine Maintenance | Overall Survival (OS) | 4.6 months |
Secondary
Percentage of Participants With Best Objective CNS Response, Assessed by Investigator According to MRI
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.
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)
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| WBRT Followed by Standard of Care | Percentage of Participants With Best Objective CNS Response, Assessed by Investigator According to MRI | 50.0 percentage of participants |
| WBRT+Capecitabine Followed by Capecitabine Maintenance | Percentage of Participants With Best Objective CNS Response, Assessed by Investigator According to MRI | 54.5 percentage of participants |
Secondary
Percentage of Participants With Best Objective Extra-cranial Disease Response, Assessed by Investigator According to Computed Tomography (CT)
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.
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)
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| WBRT Followed by Standard of Care | Percentage of Participants With Best Objective Extra-cranial Disease Response, Assessed by Investigator According to Computed Tomography (CT) | 0.0 percentage of participants |
| WBRT+Capecitabine Followed by Capecitabine Maintenance | Percentage of Participants With Best Objective Extra-cranial Disease Response, Assessed by Investigator According to Computed Tomography (CT) | 9.1 percentage of participants |
Secondary
Percentage of Participants With Clinical Benefit, Assessed by Investigator According to MRI
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.
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)
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| WBRT Followed by Standard of Care | Percentage of Participants With Clinical Benefit, Assessed by Investigator According to MRI | 83.3 percentage of participants |
| WBRT+Capecitabine Followed by Capecitabine Maintenance | Percentage of Participants With Clinical Benefit, Assessed by Investigator According to MRI | 72.7 percentage of participants |
Secondary
Percentage of Participants With Objective CNS Response at 4 Weeks After Completion of WBRT, Assessed by Centralized Independent Expert According to MRI
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.
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)
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| WBRT Followed by Standard of Care | Percentage of Participants With Objective CNS Response at 4 Weeks After Completion of WBRT, Assessed by Centralized Independent Expert According to MRI | 25.0 percentage of participants |
| WBRT+Capecitabine Followed by Capecitabine Maintenance | Percentage of Participants With Objective CNS Response at 4 Weeks After Completion of WBRT, Assessed by Centralized Independent Expert According to MRI | 36.4 percentage of participants |
Secondary
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
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.
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)
Population: The data for this outcome was not collected as per changes in planned analysis because sufficient information on the method used was not available.
Secondary
Percentage of Participants With Objective CNS Response at 4 Weeks After Completion of WBRT, Assessed by Investigator According to MRI
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.
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)
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| WBRT Followed by Standard of Care | Percentage of Participants With Objective CNS Response at 4 Weeks After Completion of WBRT, Assessed by Investigator According to MRI | 41.7 percentage of participants |
| WBRT+Capecitabine Followed by Capecitabine Maintenance | Percentage of Participants With Objective CNS Response at 4 Weeks After Completion of WBRT, Assessed by Investigator According to MRI | 27.3 percentage of participants |
Secondary
Percentage of Participants With Objective Extra-cranial Disease Response at 4 Weeks After Completion of WBRT, Assessed by Investigator According to CT
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 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)
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| WBRT Followed by Standard of Care | Percentage of Participants With Objective Extra-cranial Disease Response at 4 Weeks After Completion of WBRT, Assessed by Investigator According to CT | 0.0 percentage of participants |
| WBRT+Capecitabine Followed by Capecitabine Maintenance | Percentage of Participants With Objective Extra-cranial Disease Response at 4 Weeks After Completion of WBRT, Assessed by Investigator According to CT | 9.1 percentage of participants |
Secondary
Time to CNS Progression, Assessed by Investigator According to MRI
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.
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)
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| WBRT Followed by Standard of Care | Time to CNS Progression, Assessed by Investigator According to MRI | 3.8 months |
| WBRT+Capecitabine Followed by Capecitabine Maintenance | Time to CNS Progression, Assessed by Investigator According to MRI | 3.4 months |
Secondary
Time to Extra-cranial Disease Progression, Assessed by Investigator According to CT
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 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)
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| WBRT Followed by Standard of Care | Time to Extra-cranial Disease Progression, Assessed by Investigator According to CT | 3.5 months |
| WBRT+Capecitabine Followed by Capecitabine Maintenance | Time to Extra-cranial Disease Progression, Assessed by Investigator According to CT | 2.7 months |
Secondary
Time to Progression, Assessed by Investigator According to MRI and CT
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.
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)
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| WBRT Followed by Standard of Care | Time to Progression, Assessed by Investigator According to MRI and CT | 3.3 months |
| WBRT+Capecitabine Followed by Capecitabine Maintenance | Time to Progression, Assessed by Investigator According to MRI and CT | 2.7 months |