Trial Outcomes & Findings for A Study of Whole Brain Radiation Therapy and Capecitabine in Breast Cancer Participants With Newly Diagnosed Brain Metastasis (NCT NCT00977379)

Last Updated: 2016-11-15

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

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)

Results posted on

2016-11-15

Participant Flow

Participant milestones

Participant milestones
Measure	WBRT Followed by Standard of Care Participants received 3000 centi-Gray (cGy) whole brain radiation therapy (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 (central nervous system \[CNS\] or extra-cranial tumor progression, unacceptable toxicity, change of therapeutic strategy, withdrawal of participant consent, or death).	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 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).
Overall Study STARTED	12	12
Overall Study Treated	12	11
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	12	12

Reasons for withdrawal

Reasons for withdrawal
Measure	WBRT Followed by Standard of Care Participants received 3000 centi-Gray (cGy) whole brain radiation therapy (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 (central nervous system \[CNS\] or extra-cranial tumor progression, unacceptable toxicity, change of therapeutic strategy, withdrawal of participant consent, or death).	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 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).
Overall Study Withdrawal by Subject	1	1
Overall Study Death	7	9
Overall Study Premature Study Termination	4	0
Overall Study Participant Moving House	0	1
Overall Study Randomization Error	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	WBRT Followed by Standard of Care n=12 Participants 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).	WBRT+Capecitabine Followed by Capecitabine Maintenance n=11 Participants 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).	Total n=23 Participants Total of all reporting groups
Age, Continuous	54.8 years STANDARD_DEVIATION 15.6 • n=99 Participants	57.8 years STANDARD_DEVIATION 13.1 • n=107 Participants	56.2 years STANDARD_DEVIATION 14.2 • n=206 Participants
Sex: Female, Male Female	12 Participants n=99 Participants	11 Participants n=107 Participants	23 Participants n=206 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	WBRT Followed by Standard of Care n=12 Participants 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).	WBRT+Capecitabine Followed by Capecitabine Maintenance n=11 Participants 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).
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	36.4 percentage of participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	WBRT Followed by Standard of Care n=10 Participants 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).	WBRT+Capecitabine Followed by Capecitabine Maintenance n=9 Participants 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).
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	33.3 percentage of participants

SECONDARY outcome

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	WBRT Followed by Standard of Care n=12 Participants 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).	WBRT+Capecitabine Followed by Capecitabine Maintenance n=11 Participants 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).
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	36.4 percentage of participants

SECONDARY outcome

Population: ITT population.

Outcome measures

Outcome measures
Measure	WBRT Followed by Standard of Care n=12 Participants 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).	WBRT+Capecitabine Followed by Capecitabine Maintenance n=11 Participants 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).
Percentage of Participants With Best Objective CNS Response, Assessed by Investigator According to MRI	50.0 percentage of participants	54.5 percentage of participants

SECONDARY outcome

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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	WBRT Followed by Standard of Care n=12 Participants 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).	WBRT+Capecitabine Followed by Capecitabine Maintenance n=11 Participants 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).
Percentage of Participants With Clinical Benefit, Assessed by Investigator According to MRI	83.3 percentage of participants	72.7 percentage of participants

SECONDARY outcome

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	WBRT Followed by Standard of Care n=12 Participants 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).	WBRT+Capecitabine Followed by Capecitabine Maintenance n=11 Participants 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).
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	27.3 percentage of participants

SECONDARY outcome

Population: ITT population. Here, number of participants analyzed = participants having had a CR or PR during the study.

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.

Outcome measures

Outcome measures
Measure	WBRT Followed by Standard of Care n=6 Participants 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).	WBRT+Capecitabine Followed by Capecitabine Maintenance n=6 Participants 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).
Duration of CNS Response, Assessed by Investigator According to MRI	6.2 months Interval 0.0 to 16.0	2.6 months Interval 0.0 to 11.0

SECONDARY outcome

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	WBRT Followed by Standard of Care n=12 Participants 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).	WBRT+Capecitabine Followed by Capecitabine Maintenance n=11 Participants 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).
Time to CNS Progression, Assessed by Investigator According to MRI	3.8 months Interval 1.0 to 17.0	3.4 months Interval 1.0 to 15.0

SECONDARY outcome

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	WBRT Followed by Standard of Care n=12 Participants 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).	WBRT+Capecitabine Followed by Capecitabine Maintenance n=11 Participants 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).
Percentage of Participants With Best Objective Extra-cranial Disease Response, Assessed by Investigator According to Computed Tomography (CT)	0.0 percentage of participants	9.1 percentage of participants

SECONDARY outcome

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	WBRT Followed by Standard of Care n=12 Participants 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).	WBRT+Capecitabine Followed by Capecitabine Maintenance n=11 Participants 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).
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	9.1 percentage of participants

SECONDARY outcome

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	WBRT Followed by Standard of Care n=12 Participants 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).	WBRT+Capecitabine Followed by Capecitabine Maintenance n=11 Participants 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).
Time to Extra-cranial Disease Progression, Assessed by Investigator According to CT	3.5 months Interval 1.0 to 10.0	2.7 months Interval 1.0 to 15.0

SECONDARY outcome

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	WBRT Followed by Standard of Care n=12 Participants 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).	WBRT+Capecitabine Followed by Capecitabine Maintenance n=11 Participants 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).
Time to Progression, Assessed by Investigator According to MRI and CT	3.3 months Interval 1.0 to 10.0	2.7 months Interval 1.0 to 15.0

SECONDARY outcome

Timeframe: Baseline until death (up to approximately 1 year 5.5 months overall)

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	WBRT Followed by Standard of Care n=12 Participants 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).	WBRT+Capecitabine Followed by Capecitabine Maintenance n=11 Participants 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).
Overall Survival (OS)	9.8 months Interval 4.3 to 17.0	4.6 months Interval 2.3 to 8.9

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	WBRT Followed by Standard of Care n=10 Participants 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).	WBRT+Capecitabine Followed by Capecitabine Maintenance n=8 Participants 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).
Absolute Change From Baseline in Mini Mental State (MMS) Total Score	-1.5 units on a scale Standard Deviation 4.3	0.9 units on a scale Standard Deviation 3.2

Adverse Events

WBRT Followed by Standard of Care

Serious events: 6 serious events

Other events: 11 other events

Deaths: 0 deaths

WBRT+Capecitabine Followed by Capecitabine Maintenance

Serious events: 6 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	WBRT Followed by Standard of Care n=12 participants at risk 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).	WBRT+Capecitabine Followed by Capecitabine Maintenance n=11 participants at risk 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).
Gastrointestinal disorders Colitis	0.00% 0/12 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.	9.1% 1/11 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.
General disorders Asthenia	8.3% 1/12 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.	0.00% 0/11 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.
General disorders Chest pain	8.3% 1/12 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.	0.00% 0/11 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.
General disorders General physical health deterioration	8.3% 1/12 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.	18.2% 2/11 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.
Nervous system disorders Cerebrovascular accident	8.3% 1/12 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.	0.00% 0/11 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.
Nervous system disorders Depressed level of consciousness	0.00% 0/12 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.	9.1% 1/11 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.
Nervous system disorders Epilepsy	8.3% 1/12 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.	9.1% 1/11 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.
Nervous system disorders Intracranial pressure increased	0.00% 0/12 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.	9.1% 1/11 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.
Nervous system disorders Myoclonus	8.3% 1/12 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.	0.00% 0/11 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.
Nervous system disorders Syncope	0.00% 0/12 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.	9.1% 1/11 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.
Psychiatric disorders Completed suicide	0.00% 0/12 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.	9.1% 1/11 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.
Respiratory, thoracic and mediastinal disorders Pleural effusion	8.3% 1/12 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.	0.00% 0/11 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/12 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.	9.1% 1/11 • Throughout study (up to approximately 1 year 5.5 months overall) Safety population included all participants from "WBRT Followed by Standard of Care" arm who received at least one fraction of WBRT and all participants from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who received at least one dose of capecitabine or one fraction of WBRT.

Other adverse events

Additional Information

Medical Communications

Hoffman-La Roche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER