Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Nervous System Diseases

Neoplasm Metastasis

Breast Neoplasms

Brain Neoplasms

Breast Diseases

Skin Diseases

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Antimetabolites

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).

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).

3000 cGy WBRT in 10 single daily fractions over 12 to 14 days (300 cGy / fraction).

WBRT

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.

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.

Standard of Care

Clinical Trials

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.

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

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

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.

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.

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.

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.

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.

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 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 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.

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.

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 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 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.

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.

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.

Hoffmann-La Roche

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.

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 Followed by Standard of Care

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).

WBRT+Capecitabine Followed by Capecitabine Maintenance

Total

Age, Continuous

Sex: Female, Male

Intent to treat (ITT) population included all randomized participants except one participant from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who was randomized by error.

Study was prematurely terminated due to an insufficient number of participants enrolled and therefore results are only based on a small sample of breast cancer participants with newly diagnosed brain metastasis and should be considered with caution.

Medical Communications

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

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.

Percentage of Participants With Best Objective CNS Response, Assessed by Centralized Independent Expert According to MRI - Per-Protocol (PP) Population

Percentage of Participants With Objective CNS Response at 4 Weeks After Completion of WBRT, Assessed by Centralized Independent Expert According to MRI

Percentage of Participants With Best Objective CNS Response, Assessed by Investigator According to MRI

The data for this outcome was not collected as per changes in planned analysis because sufficient information on the method used was not available.

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

Percentage of Participants With Clinical Benefit, Assessed by Investigator According to MRI

Percentage of Participants With Objective CNS Response at 4 Weeks After Completion of WBRT, Assessed by Investigator According to MRI

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

Duration of CNS Response, Assessed by Investigator According to MRI

Time to CNS Progression, Assessed by Investigator According to MRI

Percentage of Participants With Best Objective Extra-cranial Disease Response, Assessed by Investigator According to Computed Tomography (CT)

Percentage of Participants With Objective Extra-cranial Disease Response at 4 Weeks After Completion of WBRT, Assessed by Investigator According to CT

Time to Extra-cranial Disease Progression, Assessed by Investigator According to CT

Time to Progression, Assessed by Investigator According to MRI and CT

Overall Survival (OS)

ITT population. Here, number of participants analyzed = participants evaluable for this outcome.

Absolute Change From Baseline in Mini Mental State (MMS) Total Score

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).

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).

Spots Global Cancer Trial Database for A Study of Whole Brain Radiation Therapy and Capecitabine in Breast Cancer Participants With Newly Diagnosed Brain Metastasis

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